Cutis

To the Editor:
Patients with nonmelanoma skin cancers exhibit high quality-of-life satisfaction after treatment with Mohs micrographic surgery (MMS) or excision.^1,2 However, perioperative anxiety in patients undergoing MMS is common, especially during the immediate preoperative period.³ Anxiety activates the sympathetic nervous system, resulting in physiologic changes such as tachycardia and hypertension.^4,5 These sequelae may not only increase patient distress but also increase intraoperative bleeding, complication rates, and recovery times.^4,5 Thus, the preoperative period represents a critical window for interventions aimed at reducing anxiety. Anxiety peaks during the perioperative period for a myriad of reasons, including anticipation of pain or potential complications. Enhancing patient comfort and well-being during the procedure may help reduce negative emotional sequelae, alleviate fear during procedures, and increase patient satisfaction.³

Weighted blankets (WBs) frequently are utilized in occupational and physical therapy as a deep pressure stimulation tool to alleviate anxiety by mimicking the experience of being massaged or swaddled.⁶ Deep pressure tools increase parasympathetic tone, help reduce anxiety, and provide a calming effect.^7,8 Nonhospitalized individuals were more relaxed during mental health evaluations when using a WB, and deep pressure tools have frequently been used to calm individuals with autism spectrum disorders or attention-deficit/hyperactivity disorders.⁶ Furthermore, WBs have successfully been used to reduce anxiety in mental health care settings, as well as during chemotherapy infusions.^6,9 The literature is sparse regarding the use of WB in the perioperative setting. Potential benefit has been demonstrated in the setting of dental cleanings and wisdom teeth extractions.^7,8 In the current study, we investigated whether use of a WB could reduce preoperative anxiety in the setting of MMS.

Institutional review board approval was obtained from the University of Virginia (Charlottesville, Virginia), and adult patients undergoing MMS to the head or neck were recruited to participate in a single-blind randomized controlled trial in the spring of 2023. Patients undergoing MMS on other areas of the body were excluded because the placement of the WB could interfere with the procedure. Other exclusion criteria included pregnancy, dementia, or current treatment with an anxiolytic medication.

Twenty-seven patients were included in the study, and informed consent was obtained. Patients were randomized to use a WB or standard hospital towel (control). The medical-grade WBs weighed 8.5 pounds, while the cotton hospital towels weighed less than 1 pound. The WBs were cleaned in between patients with standard germicidal disposable wipes.

Patient data were collected from electronic medical records including age, sex, weight, history of prior MMS, and current use of antihypertensives and/or beta-blockers. Data also were collected on the presence of anxiety disorders, major depression, fibromyalgia, tobacco and alcohol use, hyperthyroidism, hyperhidrosis, cardiac arrhythmias (including atrial fibrillation), chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, peripheral neuropathy, and menopausal symptoms.

During the procedure, anxiety was monitored using the State-Trait Anxiety Inventory (STAI) Form Y-1, the visual analogue scale for anxiety (VAS-A), and vital signs including heart rate, blood pressure, and respiratory rate. Vital signs were evaluated by nursing staff with the patient sitting up and the WB or hospital towel removed. Using these assessments, anxiety was measured at 3 different timepoints: upon arrival to the clinic (timepoint A), after the patient rested in a reclined beach-chair position with the WB or hospital towel placed over them for 10 minutes before administration of local anesthetic and starting the procedure (timepoint B), and after the first MMS stage was taken (timepoint C).

A power analysis was not completed due to a lack of previous studies on the use of WBs during MMS. Group means were analyzed using two-tailed t-tests and one-way analysis of variance. A P value of .05 indicated statistical significance.

Fourteen patients were randomized to the WB group and 13 were randomized to the control group. Patient demographics are outlined in the eTable. In the WB group, mean STAI scores progressively decreased at each timepoint (A: 15.3, B: 13.6, C: 12.7) and mean VAS-A scores followed a similar trend (A: 24.2, B: 19.3, C: 10.5). In the control group, the mean STAI scores remained stable at timepoints A and B (17.7) and then decreased at timepoint C (14.8). The mean VAS-A scores in the control group followed a similar pattern, remaining stable at timepoints A (22.9) and B (22.8) and then decreasing at timepoint C (14.4). These changes were not statistically significant.

Mean vital signs for both the WB and control groups were relatively stable across all timepoints, although they tended to decrease by timepoint C. In the WB group, mean heart rates were 69, 69, and 67 beats per minute at timepoints A, B, and C, respectively. Mean systolic blood pressures were 137 mm Hg, 138 mm Hg, and 136 mm Hg and mean diastolic pressures were 71 mm Hg, 68 mm Hg, and 66 mm Hg at timepoints A, B, and C, respectively. Mean respiratory rates were 20, 19, and 18 breaths per minute at timepoints A, B, and C, respectively. In the control group, mean heart rates were 70, 69, and 68 beats per minute across timepoints A, B, and C, respectively. Mean systolic blood pressures were 137 mm Hg, 138 mm Hg, and 133 mm Hg and mean diastolic pressures were 71 mm Hg, 74 mm Hg, and 68 mm Hg at timepoints A, B, and C, respectively. Mean respiratory rates were 19, 18, and 18 breaths per minute at timepoints A, B, and C, respectively. These changes were not statistically significant.

Our pilot study examined the effects of using a WB to alleviate preoperative anxiety during MMS. Our results suggest that WBs may modestly improve subjective anxiety immediately prior to undergoing MMS. Mean STAI and VAS-A scores decreased from timepoint A to timepoint B in the WB group vs the control group in which these scores remained stable. Although our study was not powered to determine statistical differences and significance was not reached, our results suggest a favorable trend in decreased anxiety scores. Our analysis was limited by a small sample size; therefore, additional larger-scale studies will be needed to confirm this trend.

Our results are broadly consistent with earlier studies that found improvement in physiologic proxies of anxiety with the use of WBs during chemotherapy infusions, dental procedures, and acute inpatient mental health hospitalizations.^7-10 During periods of high anxiety, use of WBs shifts the autonomic nervous system from a sympathetic to a parasympathetic state, as demonstrated by increased high-frequency heart rate variability, a marker of parasympathetic activity.^6,11 While the exact mechanism of how WBs and other deep pressure stimulation tools affect high-frequency heart rate variability is unclear, one study showed that patients undergoing dental extractions were better equipped when using deep pressure stimulation tools to utilize calming techniques and regulate stress.¹² The use of WBs and other deep pressure stimulation tools may extend beyond the perioperative setting and also may be an effective tool for clinicians in other settings (eg, clinic visits, physical examinations).

In our study, all participants demonstrated the greatest reduction in anxiety at timepoint C after the first MMS stage, likely related to patients relaxing more after knowing what to expect from the surgery; this also may have been reflected somewhat in the slight downward trend noted in vital signs across both study groups. One concern regarding WB use in surgical settings is whether the added pressure could trigger unfavorable circulatory effects, such as elevated blood pressure. In our study, with the exception of diastolic blood pressure, vital signs appeared unaffected by the type of blanket used and remained relatively stable from timepoint A to timepoint B and decreased at timepoint C. Diastolic blood pressure in the WB group decreased from timepoint A to timepoint B, then decreased further from timepoint B to timepoint C. This mirrored the decreasing STAI score trend, compared to the control group who increased from timepoint A to timepoint B and reached a nadir at timepoint C. Consistent with prior WB studies, there were no adverse effects from WBs, including adverse impacts on vital signs.^6,9

The original recruitment goal was not met due to staffing issues related to the COVID-19 pandemic, and subgroup analyses were deferred as a result of sample size limitations. It is possible that the WB intervention may have a larger impact on subpopulations more prone to perioperative anxiety (eg, patients undergoing MMS for the first time). However, the results of our pilot study suggest a beneficial effect from the use of WBs. While these preliminary data are promising, additional studies in the perioperative setting are needed to more accurately determine the clinical utility of WBs during MMS and other procedures.

To the Editor:
Patients with nonmelanoma skin cancers exhibit high quality-of-life satisfaction after treatment with Mohs micrographic surgery (MMS) or excision.^1,2 However, perioperative anxiety in patients undergoing MMS is common, especially during the immediate preoperative period.³ Anxiety activates the sympathetic nervous system, resulting in physiologic changes such as tachycardia and hypertension.^4,5 These sequelae may not only increase patient distress but also increase intraoperative bleeding, complication rates, and recovery times.^4,5 Thus, the preoperative period represents a critical window for interventions aimed at reducing anxiety. Anxiety peaks during the perioperative period for a myriad of reasons, including anticipation of pain or potential complications. Enhancing patient comfort and well-being during the procedure may help reduce negative emotional sequelae, alleviate fear during procedures, and increase patient satisfaction.³

Weighted blankets (WBs) frequently are utilized in occupational and physical therapy as a deep pressure stimulation tool to alleviate anxiety by mimicking the experience of being massaged or swaddled.⁶ Deep pressure tools increase parasympathetic tone, help reduce anxiety, and provide a calming effect.^7,8 Nonhospitalized individuals were more relaxed during mental health evaluations when using a WB, and deep pressure tools have frequently been used to calm individuals with autism spectrum disorders or attention-deficit/hyperactivity disorders.⁶ Furthermore, WBs have successfully been used to reduce anxiety in mental health care settings, as well as during chemotherapy infusions.^6,9 The literature is sparse regarding the use of WB in the perioperative setting. Potential benefit has been demonstrated in the setting of dental cleanings and wisdom teeth extractions.^7,8 In the current study, we investigated whether use of a WB could reduce preoperative anxiety in the setting of MMS.

Institutional review board approval was obtained from the University of Virginia (Charlottesville, Virginia), and adult patients undergoing MMS to the head or neck were recruited to participate in a single-blind randomized controlled trial in the spring of 2023. Patients undergoing MMS on other areas of the body were excluded because the placement of the WB could interfere with the procedure. Other exclusion criteria included pregnancy, dementia, or current treatment with an anxiolytic medication.

Twenty-seven patients were included in the study, and informed consent was obtained. Patients were randomized to use a WB or standard hospital towel (control). The medical-grade WBs weighed 8.5 pounds, while the cotton hospital towels weighed less than 1 pound. The WBs were cleaned in between patients with standard germicidal disposable wipes.

Patient data were collected from electronic medical records including age, sex, weight, history of prior MMS, and current use of antihypertensives and/or beta-blockers. Data also were collected on the presence of anxiety disorders, major depression, fibromyalgia, tobacco and alcohol use, hyperthyroidism, hyperhidrosis, cardiac arrhythmias (including atrial fibrillation), chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, peripheral neuropathy, and menopausal symptoms.

During the procedure, anxiety was monitored using the State-Trait Anxiety Inventory (STAI) Form Y-1, the visual analogue scale for anxiety (VAS-A), and vital signs including heart rate, blood pressure, and respiratory rate. Vital signs were evaluated by nursing staff with the patient sitting up and the WB or hospital towel removed. Using these assessments, anxiety was measured at 3 different timepoints: upon arrival to the clinic (timepoint A), after the patient rested in a reclined beach-chair position with the WB or hospital towel placed over them for 10 minutes before administration of local anesthetic and starting the procedure (timepoint B), and after the first MMS stage was taken (timepoint C).

A power analysis was not completed due to a lack of previous studies on the use of WBs during MMS. Group means were analyzed using two-tailed t-tests and one-way analysis of variance. A P value of .05 indicated statistical significance.

Fourteen patients were randomized to the WB group and 13 were randomized to the control group. Patient demographics are outlined in the eTable. In the WB group, mean STAI scores progressively decreased at each timepoint (A: 15.3, B: 13.6, C: 12.7) and mean VAS-A scores followed a similar trend (A: 24.2, B: 19.3, C: 10.5). In the control group, the mean STAI scores remained stable at timepoints A and B (17.7) and then decreased at timepoint C (14.8). The mean VAS-A scores in the control group followed a similar pattern, remaining stable at timepoints A (22.9) and B (22.8) and then decreasing at timepoint C (14.4). These changes were not statistically significant.

Mean vital signs for both the WB and control groups were relatively stable across all timepoints, although they tended to decrease by timepoint C. In the WB group, mean heart rates were 69, 69, and 67 beats per minute at timepoints A, B, and C, respectively. Mean systolic blood pressures were 137 mm Hg, 138 mm Hg, and 136 mm Hg and mean diastolic pressures were 71 mm Hg, 68 mm Hg, and 66 mm Hg at timepoints A, B, and C, respectively. Mean respiratory rates were 20, 19, and 18 breaths per minute at timepoints A, B, and C, respectively. In the control group, mean heart rates were 70, 69, and 68 beats per minute across timepoints A, B, and C, respectively. Mean systolic blood pressures were 137 mm Hg, 138 mm Hg, and 133 mm Hg and mean diastolic pressures were 71 mm Hg, 74 mm Hg, and 68 mm Hg at timepoints A, B, and C, respectively. Mean respiratory rates were 19, 18, and 18 breaths per minute at timepoints A, B, and C, respectively. These changes were not statistically significant.

Our pilot study examined the effects of using a WB to alleviate preoperative anxiety during MMS. Our results suggest that WBs may modestly improve subjective anxiety immediately prior to undergoing MMS. Mean STAI and VAS-A scores decreased from timepoint A to timepoint B in the WB group vs the control group in which these scores remained stable. Although our study was not powered to determine statistical differences and significance was not reached, our results suggest a favorable trend in decreased anxiety scores. Our analysis was limited by a small sample size; therefore, additional larger-scale studies will be needed to confirm this trend.

Our results are broadly consistent with earlier studies that found improvement in physiologic proxies of anxiety with the use of WBs during chemotherapy infusions, dental procedures, and acute inpatient mental health hospitalizations.^7-10 During periods of high anxiety, use of WBs shifts the autonomic nervous system from a sympathetic to a parasympathetic state, as demonstrated by increased high-frequency heart rate variability, a marker of parasympathetic activity.^6,11 While the exact mechanism of how WBs and other deep pressure stimulation tools affect high-frequency heart rate variability is unclear, one study showed that patients undergoing dental extractions were better equipped when using deep pressure stimulation tools to utilize calming techniques and regulate stress.¹² The use of WBs and other deep pressure stimulation tools may extend beyond the perioperative setting and also may be an effective tool for clinicians in other settings (eg, clinic visits, physical examinations).

In our study, all participants demonstrated the greatest reduction in anxiety at timepoint C after the first MMS stage, likely related to patients relaxing more after knowing what to expect from the surgery; this also may have been reflected somewhat in the slight downward trend noted in vital signs across both study groups. One concern regarding WB use in surgical settings is whether the added pressure could trigger unfavorable circulatory effects, such as elevated blood pressure. In our study, with the exception of diastolic blood pressure, vital signs appeared unaffected by the type of blanket used and remained relatively stable from timepoint A to timepoint B and decreased at timepoint C. Diastolic blood pressure in the WB group decreased from timepoint A to timepoint B, then decreased further from timepoint B to timepoint C. This mirrored the decreasing STAI score trend, compared to the control group who increased from timepoint A to timepoint B and reached a nadir at timepoint C. Consistent with prior WB studies, there were no adverse effects from WBs, including adverse impacts on vital signs.^6,9

The original recruitment goal was not met due to staffing issues related to the COVID-19 pandemic, and subgroup analyses were deferred as a result of sample size limitations. It is possible that the WB intervention may have a larger impact on subpopulations more prone to perioperative anxiety (eg, patients undergoing MMS for the first time). However, the results of our pilot study suggest a beneficial effect from the use of WBs. While these preliminary data are promising, additional studies in the perioperative setting are needed to more accurately determine the clinical utility of WBs during MMS and other procedures.

To the Editor:
Patients with nonmelanoma skin cancers exhibit high quality-of-life satisfaction after treatment with Mohs micrographic surgery (MMS) or excision.^1,2 However, perioperative anxiety in patients undergoing MMS is common, especially during the immediate preoperative period.³ Anxiety activates the sympathetic nervous system, resulting in physiologic changes such as tachycardia and hypertension.^4,5 These sequelae may not only increase patient distress but also increase intraoperative bleeding, complication rates, and recovery times.^4,5 Thus, the preoperative period represents a critical window for interventions aimed at reducing anxiety. Anxiety peaks during the perioperative period for a myriad of reasons, including anticipation of pain or potential complications. Enhancing patient comfort and well-being during the procedure may help reduce negative emotional sequelae, alleviate fear during procedures, and increase patient satisfaction.³

Weighted blankets (WBs) frequently are utilized in occupational and physical therapy as a deep pressure stimulation tool to alleviate anxiety by mimicking the experience of being massaged or swaddled.⁶ Deep pressure tools increase parasympathetic tone, help reduce anxiety, and provide a calming effect.^7,8 Nonhospitalized individuals were more relaxed during mental health evaluations when using a WB, and deep pressure tools have frequently been used to calm individuals with autism spectrum disorders or attention-deficit/hyperactivity disorders.⁶ Furthermore, WBs have successfully been used to reduce anxiety in mental health care settings, as well as during chemotherapy infusions.^6,9 The literature is sparse regarding the use of WB in the perioperative setting. Potential benefit has been demonstrated in the setting of dental cleanings and wisdom teeth extractions.^7,8 In the current study, we investigated whether use of a WB could reduce preoperative anxiety in the setting of MMS.

Institutional review board approval was obtained from the University of Virginia (Charlottesville, Virginia), and adult patients undergoing MMS to the head or neck were recruited to participate in a single-blind randomized controlled trial in the spring of 2023. Patients undergoing MMS on other areas of the body were excluded because the placement of the WB could interfere with the procedure. Other exclusion criteria included pregnancy, dementia, or current treatment with an anxiolytic medication.

Twenty-seven patients were included in the study, and informed consent was obtained. Patients were randomized to use a WB or standard hospital towel (control). The medical-grade WBs weighed 8.5 pounds, while the cotton hospital towels weighed less than 1 pound. The WBs were cleaned in between patients with standard germicidal disposable wipes.

Patient data were collected from electronic medical records including age, sex, weight, history of prior MMS, and current use of antihypertensives and/or beta-blockers. Data also were collected on the presence of anxiety disorders, major depression, fibromyalgia, tobacco and alcohol use, hyperthyroidism, hyperhidrosis, cardiac arrhythmias (including atrial fibrillation), chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, peripheral neuropathy, and menopausal symptoms.

During the procedure, anxiety was monitored using the State-Trait Anxiety Inventory (STAI) Form Y-1, the visual analogue scale for anxiety (VAS-A), and vital signs including heart rate, blood pressure, and respiratory rate. Vital signs were evaluated by nursing staff with the patient sitting up and the WB or hospital towel removed. Using these assessments, anxiety was measured at 3 different timepoints: upon arrival to the clinic (timepoint A), after the patient rested in a reclined beach-chair position with the WB or hospital towel placed over them for 10 minutes before administration of local anesthetic and starting the procedure (timepoint B), and after the first MMS stage was taken (timepoint C).

A power analysis was not completed due to a lack of previous studies on the use of WBs during MMS. Group means were analyzed using two-tailed t-tests and one-way analysis of variance. A P value of .05 indicated statistical significance.

Fourteen patients were randomized to the WB group and 13 were randomized to the control group. Patient demographics are outlined in the eTable. In the WB group, mean STAI scores progressively decreased at each timepoint (A: 15.3, B: 13.6, C: 12.7) and mean VAS-A scores followed a similar trend (A: 24.2, B: 19.3, C: 10.5). In the control group, the mean STAI scores remained stable at timepoints A and B (17.7) and then decreased at timepoint C (14.8). The mean VAS-A scores in the control group followed a similar pattern, remaining stable at timepoints A (22.9) and B (22.8) and then decreasing at timepoint C (14.4). These changes were not statistically significant.

Mean vital signs for both the WB and control groups were relatively stable across all timepoints, although they tended to decrease by timepoint C. In the WB group, mean heart rates were 69, 69, and 67 beats per minute at timepoints A, B, and C, respectively. Mean systolic blood pressures were 137 mm Hg, 138 mm Hg, and 136 mm Hg and mean diastolic pressures were 71 mm Hg, 68 mm Hg, and 66 mm Hg at timepoints A, B, and C, respectively. Mean respiratory rates were 20, 19, and 18 breaths per minute at timepoints A, B, and C, respectively. In the control group, mean heart rates were 70, 69, and 68 beats per minute across timepoints A, B, and C, respectively. Mean systolic blood pressures were 137 mm Hg, 138 mm Hg, and 133 mm Hg and mean diastolic pressures were 71 mm Hg, 74 mm Hg, and 68 mm Hg at timepoints A, B, and C, respectively. Mean respiratory rates were 19, 18, and 18 breaths per minute at timepoints A, B, and C, respectively. These changes were not statistically significant.

Our pilot study examined the effects of using a WB to alleviate preoperative anxiety during MMS. Our results suggest that WBs may modestly improve subjective anxiety immediately prior to undergoing MMS. Mean STAI and VAS-A scores decreased from timepoint A to timepoint B in the WB group vs the control group in which these scores remained stable. Although our study was not powered to determine statistical differences and significance was not reached, our results suggest a favorable trend in decreased anxiety scores. Our analysis was limited by a small sample size; therefore, additional larger-scale studies will be needed to confirm this trend.

Our results are broadly consistent with earlier studies that found improvement in physiologic proxies of anxiety with the use of WBs during chemotherapy infusions, dental procedures, and acute inpatient mental health hospitalizations.^7-10 During periods of high anxiety, use of WBs shifts the autonomic nervous system from a sympathetic to a parasympathetic state, as demonstrated by increased high-frequency heart rate variability, a marker of parasympathetic activity.^6,11 While the exact mechanism of how WBs and other deep pressure stimulation tools affect high-frequency heart rate variability is unclear, one study showed that patients undergoing dental extractions were better equipped when using deep pressure stimulation tools to utilize calming techniques and regulate stress.¹² The use of WBs and other deep pressure stimulation tools may extend beyond the perioperative setting and also may be an effective tool for clinicians in other settings (eg, clinic visits, physical examinations).

In our study, all participants demonstrated the greatest reduction in anxiety at timepoint C after the first MMS stage, likely related to patients relaxing more after knowing what to expect from the surgery; this also may have been reflected somewhat in the slight downward trend noted in vital signs across both study groups. One concern regarding WB use in surgical settings is whether the added pressure could trigger unfavorable circulatory effects, such as elevated blood pressure. In our study, with the exception of diastolic blood pressure, vital signs appeared unaffected by the type of blanket used and remained relatively stable from timepoint A to timepoint B and decreased at timepoint C. Diastolic blood pressure in the WB group decreased from timepoint A to timepoint B, then decreased further from timepoint B to timepoint C. This mirrored the decreasing STAI score trend, compared to the control group who increased from timepoint A to timepoint B and reached a nadir at timepoint C. Consistent with prior WB studies, there were no adverse effects from WBs, including adverse impacts on vital signs.^6,9

The original recruitment goal was not met due to staffing issues related to the COVID-19 pandemic, and subgroup analyses were deferred as a result of sample size limitations. It is possible that the WB intervention may have a larger impact on subpopulations more prone to perioperative anxiety (eg, patients undergoing MMS for the first time). However, the results of our pilot study suggest a beneficial effect from the use of WBs. While these preliminary data are promising, additional studies in the perioperative setting are needed to more accurately determine the clinical utility of WBs during MMS and other procedures.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by uncontrolled hyperglycemia. Over the past few decades, its prevalence has steadily increased, now affecting approximately 10% of adults worldwide and ranking among the top 10 leading causes of death globally.¹ The pathophysiology of T2DM involves persistent hyperglycemia that drives insulin resistance and a progressive decline in insulin production from the pancreas.² Medical management of this condition aims to reduce blood glucose levels or enhance insulin production and sensitivity. Aside from lifestyle modifications, metformin is considered the first-line treatment for glycemic control according to the 2023 American Association of Clinical Endocrinology’s T2DM management algorithm.³ These updated guidelines stratify adjunct treatments by individualized glycemic targets and patient needs. For patients who are overweight or obese, glucagonlike peptide 1 (GLP-1) and dual GLP-1/ gastric inhibitory polypeptide (GIP) agonists are the preferred adjunct or second-line treatments.³

In this review, we highlight the dermatologic adverse effects and potential therapeutic benefits of metformin as well as GLP-1 and GLP-1/GIP agonists.

METFORMIN

Metformin is a biguanide agent used as a first-line treatment for T2DM because of its ability to reduce hepatic glucose production and increase peripheral tissue glucose uptake.⁴ In addition to its effects on glucose, metformin has been shown to have anti-inflammatory properties via inhibition of the nuclear factor κB and mammalian target of rapamycin (mTOR) pathways, leading to decreased production of cytokines associated with T helper (Th) 1 and Th17 cell responses, such as IL-17, interferon gamma (IFN-γ), and tumor necrosis factor α (TNF-α).^5-7 These findings have spurred interest among clinicians in the potential use of metformin for inflammatory conditions, including dermatologic diseases such as psoriasis and hidradenitis suppurativa (HS).⁸

Adverse Effects

Metformin is administered orally and generally is well tolerated. The most common adverse effects include gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain.⁹ While cutaneous adverse effects are rare, multiple dermatologic adverse reactions to metformin have been reported,^10,11 including leukocytoclastic vasculitis,^11-13 fixed drug eruptions,^14-17 drug rash with eosinophilia and systemic symptoms (DRESS) syndrome,¹⁸ and photosensitivity reactions.¹⁹ Leukocytoclastic vasculitis and DRESS syndrome typically develop within the first month following metformin initiation, while fixed drug eruption and photosensitivity reactions have more variable timing, occurring weeks to years after treatment initiation.^12-19

Dermatologic Implications

Acanthosis Nigricans—Acanthosis nigricans (AN) is characterized by hyperpigmentation and velvety skin thickening, typically in intertriginous areas such as the back of the neck, axillae, and groin.²⁰ It commonly is associated with insulin resistance and obesity.^21-23 Treatments for AN primarily center around insulin sensitivity and weight loss,^24,25 with some benefit observed from the use of keratolytic agents.^26,27 Metformin may have utility in treating AN through its effects on insulin sensitivity and glycemic control. Multiple case reports have noted marked improvements in AN in patients with and without obesity with the addition of metformin to their existing treatment regimens in doses ranging from 500 mg to 1700 mg daily.^28-30 However, an unblinded randomized controlled trial (RCT) comparing the efficacy of metformin (500 mg 3 times daily) with rosiglitazone (4 mg/d), another T2DM medication, on AN neck lesions in patients who were overweight and obese found no significant effects in lesion severity and only modest improvements in skin texture in both groups at 12 weeks following treatment initiation.³¹ Another RCT comparing metformin (500 mg twice daily) with a twice-daily capsule containing α-lipoic acid, biotin, chromium polynicotinate, and zinc sulfate, showed significant (P<.001) improvements in AN neck lesions in both groups after 12 weeks.³² According to Sung et al,⁸ longer duration of therapy (>6 months), higher doses (1700–2000 mg), and lower baseline weight were associated with higher efficacy of metformin for treatment of AN. Overall, the use of metformin as an adjunct treatment for AN, particularly in patients with underlying hyperglycemia, is supported in the literature, but further studies are needed to clarify dosing, duration of therapy, and patient populations that will benefit most from adding metformin to their treatment regimens.

Hirsutism—Hirsutism, which is characterized by excessive hair growth in androgen-dependent areas, can be challenging to treat. Metformin has been shown to reduce circulating insulin, luteinizing hormone, androstenedione, and testosterone, thus improving underlying hyperandrogenism, particularly in patients with polycystic ovary syndrome (PCOS).^33-35 Although single studies evaluating the efficacy of metformin for treatment of hirsutism in patients with PCOS have shown potential benefits,^36-38 meta-analyses showed no significant effects of metformin compared to placebo or oral contraceptives and decreased benefits compared to spironolactone and flutamide.³⁹ Given these findings showing that metformin was no more effective than placebo or other treatments, the current Endocrine Society guidelines recommend against the use of metformin for hirsutism.^39,40 There may be a role for metformin as an adjuvant therapy in certain populations (eg, patients with comorbid T2DM), although further studies stratifying risk factors such as body mass index and age are needed.⁴¹

Hidradenitis Suppurativa—Hidradenitis suppurativa is a follicular occlusive disease characterized by recurrent inflamed nodules leading to chronic dermal abscesses, fibrosis, and sinus tract formation primarily in intertriginous areas such as the axillae and groin.⁴² Medical management depends on disease severity but usually involves antibiotic treatment with adjunct therapies such as oral contraceptives, antiandrogenic medications (eg, spironolactone), biologic medications, and metformin.⁴² Preclinical and clinical data suggest that metformin can impact HS through metabolic and immunomodulatory mechanisms.^5,42 Like many chronic inflammatory disorders, HS is associated with metabolic syndrome.^43,44 A study evaluating insulin secretion after oral glucose tolerance testing showed increased insulin levels in patients with HS compared to controls (P=.02), with 60% (6/10) of patients with HS meeting criteria for insulin resistance. In addition, serum insulin levels in insulin-resistant patients with HS correlated with increased lesional skin mTOR gene expression at 30 (r=.80) and 60 (r=1.00) minutes, and mTOR was found to be upregulated in lesional and extralesional skin in patients with HS compared to healthy controls (P<.01).45 Insulin activates mTOR signaling, which mediates cell growth and survival, among other processes.⁴⁶ Thus, metformin’s ability to increase insulin sensitivity and inhibit mTOR signaling could be beneficial in the setting of HS. Additionally, insulin and insulinlike growth factor 1 (IGF-1) increase androgen signaling, a process that has been implicated in HS.⁴⁷

Metformin also may impact HS through its effects on testosterone and other hormones.⁴⁸ A study evaluating peripheral blood mononuclear cells in patients with HS showed reduced IL-17, IFN-γ, TNF-α, and IL-6 levels in patients who were taking metformin (dose not reported) for longer than 6 months compared to patients who were not on metformin. Further analysis of ex vivo HS lesions cultured with metformin showed decreased IL-17, IFN-γ, TNF-α, and IL-8 expression in tissue, suggesting an antiinflammatory role of metformin in HS.⁵

Although there are no known RCTs assessing the efficacy of metformin in HS, existing clinical data are supportive of the use of metformin for refractory HS.⁴⁹ Following a case report describing a patient with T2DM and stable HS while on metformin,⁵⁰ several cohort studies have assessed the efficacy of metformin for the treatment of HS. A prospective study evaluating the efficacy of metformin monotherapy (starting dose of 500 mg/d, titrated to 500 mg 3 times daily) in patients with and without T2DM with HS refractory to other therapies found clinical improvement in 72% (18/25) of patients using the Sartorius Hidradenitis Suppurativa Score, improving from a mean (SD) score of 34.40 (12.46) to 26.76 (11.22) at 12 weeks (P=.0055,) and 22.39 (11.30) at 24 weeks (P=.0001). Additionally, 64% (16/25) of patients showed improved quality of life as evaluated by the Dermatology Life Quality Index (DLQI), which decreased from a mean (SD) score of 15.00 (4.96) to 10.08 (5.96)(P=.0017) at 12 weeks and 7.65 (7.12)(P=.000009) at 24 weeks on treatment.⁴⁸ In a retrospective study of 53 patients with HS taking metformin started at 500 mg daily and increased to 500 mg twice daily after 2 weeks (when tolerated), 68% (36/53) showed some clinical response, with 19% (7/36) of those patients having achieved complete response to metformin monotherapy (defined as no active HS).⁵¹ Similarly, a retrospective study of pediatric patients with HS evaluating metformin (doses ranging from 500-2000 mg daily) as an adjunct therapy described a subset of patients with decreased frequency of HS flares with metformin.⁵² These studies emphasize the safety profile of metformin and support its current use as an adjunctive therapy for HS.

Acne Vulgaris—Acne vulgaris (AV) is a chronic inflammatory disorder affecting the pilosebaceous follicles.¹¹ Similar to HS, AV has metabolic and hormonal influences that can be targeted by metformin.⁵³ In AV, androgens lead to increased sebum production by binding to androgen receptors on sebocytes, which in turn attracts Cutibacterium acnes and promotes hyperkeratinization, inducing inflammation.⁵⁴ Thus, the antiandrogenic effects of metformin may be beneficial for treatment of AV. Additionally, sebocytes express receptors for insulin and IGF-1, which can increase the size and number of sebocytes, as well as promote lipogenesis and inflammatory response, influencing sebum production.⁵⁴ Serum levels for IGF-1 have been observed to be increased in patients with AV⁵⁵ and reduced by metformin.⁵⁶ A recent meta-analysis assessing the efficacy of metformin on AV indicated that 87% (13/15) of studies noted disease improvement on metformin, with 47% (7/15) of studies showing statistically significant (P<0.05) decreases in acne severity.57 Although most studies showed improvement, 47% (7/15) did not find significant differences between metformin and other interventions, indicating the availability of comparable treatment options. Overall, there has been a positive association between metformin use and acne improvement.⁵⁷ However, it is important to note that most studies have focused on females with PCOS,⁵⁷ and the main benefits of metformin in acne might be seen when managing comorbid conditions, particularly those associated with metabolic dysregulation and insulin resistance. Further studies are needed to determine the generalizability of prior results.

Psoriasis—Psoriasis is a chronic autoinflammatory disease characterized by epidermal hyperplasia with multiple cutaneous manifestations and potential for multiorgan involvement. Comorbid conditions include psoriatic arthritis, metabolic syndrome, and cardiovascular disease.⁵⁸ Current treatment options depend on several factors (eg, disease severity, location of cutaneous lesions, comorbidities) and include topical, systemic, and phototherapy options, many of which target the immune system.^58,59 A meta-analysis of 3 RCTs showed that metformin (500 mg/d or 1000 mg/d) was associated with significantly improved Psoriasis Area and Severity Index (PASI) 75% reductions (odds ratio [OR], 22.02; 95% CI, 2.12-228.49; P=.01) and 75% reductions in erythema, scaling, and induration (OR, 9.12; 95% CI, 2.13-39.02; P=.003) compared to placebo.⁶⁰ In addition, an RCT evaluating the efficacy of metformin (1000 mg/d) or pioglitazone (30 mg/d) for 12 weeks in patients with psoriasis with metabolic syndrome found significant improvements in PASI75 (P=.001) and erythema, scaling, and induration (P=.016) scores as well as in Physician Global Assessment scores (P=.012) compared to placebo and no differences compared to pioglitazone.⁶¹ While current psoriasis management guidelines do not include metformin, its use may be worth consideration as an adjunct therapy in patients with psoriasis and comorbidities such as T2DM and metabolic syndrome.⁵⁹ Metformin’s potential benefits in psoriasis may lie outside its metabolic influences and occur secondary to its immunomodulatory effects, including targeting of the Th17 axis or cytokine-specific pathways such as TNF-α, which are known to be involved in psoriasis pathogenesis.⁵⁸

Central Centrifugal Cicatricial Alopecia—Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia characterized by chronic inflammation leading to permanent loss of hair follicles on the crown of the scalp.⁶² Current treatments include topical and intralesional corticosteroids, as well as oral antibiotics. In addition, therapies including the antimalarial hydroxychloroquine and immunosuppressants mycophenolate and cyclosporine are used in refractory disease.^63,64 A case report described 2 patients with hair regrowth after 4 and 6 months of treatment with topical metformin 10% compounded in a proprietary transdermal vehicle.⁶⁵ The authors speculated that metformin’s effects on CCCA could be attributed to its known agonistic effects on the adenosine monophosphate-activated protein kinase (AMPK) pathway with subsequent reduction in inflammation-induced fibrosis.^65,66 Microarray⁶⁷ and proteomic⁶⁸ analysis have shown that AMPK is known to be downregulated in CCCA , making it an interesting therapeutic target in this disease. A recent retrospective case series demonstrated that 67% (8/12) of patients with refractory CCCA had symptomatic improvement, and 50% (6/12) showed hair regrowth after 6 months of low-dose (500 mg/d) oral metformin treatment.⁶² In addition, metformin therapy showed antifibrotic and anti-inflammatory effects when comparing scalp biopsies before and after treatment. Results showed decreased expression of fibrosisrelated genes (matrix metalloproteinase 7, collagen type IV á 1 chain), and gene set variation analysis showing reduced Th17 (P=.04) and increased AMPK signaling (P=.02) gene set expression.⁶² These findings are consistent with previous studies describing the upregulation of AMPK66 and downregulation of Th176 following metformin treatment. The immunomodulatory effects of metformin could be attributed to AMPK-mediated mTOR and NF-κB downregulation,⁶² although more studies are needed to understand these mechanisms and further explore the use of metformin in CCCA.

Skin Cancer—Metformin also has been evaluated in the setting of skin malignancies, including melanoma, squamous cell carcinoma, and basal cell carcinoma. Preclinical data suggest that metformin decreases cell viability in tumors through interactions with pathways involved in proinflammatory and prosurvival mechanisms such as NF-κB and mTOR.^69,70 Additionally, given metformin’s inhibitory effects on oxidative phosphorylation, it has been postulated that it could be used to overcome treatment resistance driven by metabolic reprogramming.^71,72 Most studies related to metformin and skin malignancies are still in preclinical stages; however, a meta-analysis of RCTs and cohort studies did not find significant associations between metformin use and skin cancer risk, although data trended toward a modest reduction in skin cancer among metformin users.⁷³ A retrospective cohort study of melanoma in patients with T2DM taking metformin (250-2000 mg/d) found that the 5-year incidence of recurrence was lower in the metformin cohort compared to nonusers (43.8% vs 58.2%, respectively)(P=.002), and overall survival rates trended upward in the higher body mass index (>30) and melanoma stages 1 and 2 groups but did not reach statistical significance.⁷⁴ In addition, a whole population casecontrol study in Iceland reported that metformin use at least 2 years before first-time basal cell carcinoma diagnosis was associated with a lower risk for disease (adjusted OR, 0.71; 95% CI, 0.61-0.83) with no significant dose-dependent differences; there were no notable effects on squamous cell carcinoma risk.⁷⁵ Further preclinical and clinical data are needed to elucidate metformin’s effects on skin malignancies.

GLP-1 AND DUAL GLP-1/GIP AGONISTS

Glucagonlike peptide 1 and dual GLP-1/GIP agonists are emerging classes of medications currently approved as adjunct and second-line therapies for T2DM, particularly in patients who are overweight or obese as well as in those who are at risk for hypoglycemia.³ Currently approved GLP-1 agonists for T2DM include semaglutide, dulaglutide, exenatide, liraglutide, and lixisenatide, while tirzepatide is the only approved dual GLP-1/GIP agonist. Activating GLP-1 and GIP receptors stimulates insulin secretion and decreases glucagon production by the pancreas, thereby reducing blood glucose levels. Additionally, some of these medications are approved for obesity given their effects in delayed gastric emptying and increased satiety, among other factors.

Over the past few years, multiple case reports have described the associations between GLP-1 agonist use and improvement of dermatologic conditions, particularly those associated with T2DM and obesity, including HS and psoriasis.^76,77 The mechanisms through which this occurs are not fully elucidated, although basic science and clinical studies have shown that GLP-1 agonists have immunomodulatory effects by reducing proinflammatory cytokines and altering immune cell populations.^77-80 The numerous ongoing clinical trials and research studies will help further elucidate their benefits in other disease settings.⁸¹

Adverse Reactions

Most GLP-1 and GLP-1/GIP agonists are administered subcutaneously, and the most commonly reported cutaneous adverse effects are injection site reactions.⁸² Anaphylactic reactions to these medications also have been reported, although it is unclear if these were specific to the active ingredients or to injection excipients.^83,84 A review of 33 cases of cutaneous reactions to GLP-1 agonists reported 11 (33%) dermal hypersensitivity reactions occurring as early as 4 weeks and as late as 3 years after treatment initiation. It also described 10 (30%) cases of eosinophilic panniculitis that developed within 3 weeks to 5 months of GLP-1 treatment, 3 (9%) cases of bullous pemphigoid that occurred within the first 2 months, 2 (6%) morbilliform drug eruptions that occurred within 5 weeks, 2 (6%) cases of angioedema that occurred 15 minutes to 2 weeks after treatment initiation, and 7 (21%) other isolated cutaneous reactions. Extended-release exenatide had the most reported reactions followed by liraglutide and subcutaneous semaglutide.⁸⁵

In a different study, semaglutide use was most commonly associated with injection site reactions followed by alopecia, especially with oral administration. Unique cases of angioedema (2 days after injection), cutaneous hypersensitivity (within 10 months on treatment), bullous pemphigoid (within 2 months on treatment), eosinophilic fasciitis (within 2 weeks on treatment), and leukocytoclastic vasculitis (unclear timing), most of which resolved after discontinuation, also were reported.⁸⁶ A recent case report linked semaglutide (0.5 mg/wk) to a case of drug-induced systemic lupus erythematosus that developed within 3 months of treatment initiation and described systemic lupus erythematosus–like symptoms in a subset of patients using this medication, namely females older than 60 years, within the first month of treatment.⁸⁷ Hyperhidrosis was listed as a common adverse event in exenatide clinical trials, and various cases of panniculitis with exenatide use have been reported.^82,88 Alopecia, mainly attributed to accelerated telogen effluvium secondary to rapid weight loss, also has been reported, although hair loss is not officially listed as an adverse effect of GLP-1 agonists, and reports are highly variable.⁸⁹ Also secondary to weight loss, facial changes including sunken eyes, development of wrinkles, sagging jowls around the neck and jaw, and a hollowed appearance, among others, are recognized as undesirable adverse effects.⁹⁰ Mansour et al⁹⁰ described the potential challenges and considerations to these rising concerns associated with GLP1-agonist use.

Dermatologic Implications

Hidradenitis Suppurativa—Weight loss commonly is recommended as a lifestyle modification in the management of HS. Multiple reports have described clinical improvement of HS following weight loss with other medical interventions, such as dietary measures and bariatric surgery.^91-94 Thus, it has been postulated that medically supported weight loss with GLP-1 agonists can help improve HS⁹⁵; however, the data on the effectiveness of GLP-1 agonists on HS are still scarce and mostly have been reported in individual patients. One case report described a patient with improvements in their recalcitrant HS and DLQI score following weight loss on liraglutide (initial dose of 0.6 mg/d, titrated to 1.8 mg/d).⁷⁶ In addition, a recent case report described improvements in HS and DLQI score following concomitant tirzepatide (initial dose of 2.5 mg/0.5 mL weekly, titrated to 7.5 mg/0.5 mL weekly) and infliximab treatment.⁹⁶ The off-label use of these medications for HS is debated, and further studies regarding the benefits of GLP-1 agonists on HS still are needed.

Psoriasis—Similarly, several case reports have commented on the effects of GLP-1 agonists on psoriasis.^97,98 An early study found GLP-1 receptors were expressed in psoriasis plaques but not in healthy skin and discussed that this could be due to immune infiltration in the plaques, providing a potential rationale for using anti-inflammatory GLP-1 agonists for psoriasis.⁹⁹ Two prospective cohort studies observed improvements in PASI and DLQI scores in patients with psoriasis and T2DM after liraglutide treatment and noted important changes in immune cell populations.^80,100 A recent RCT also found improvements in DLQI and PASI scores (P<.05) in patients with T2DM following liraglutide (1.8 mg/d) treatment, along with overall decreases in inflammatory cytokines, such as IL-23, IL-17, and TNF-α.⁷⁷ However, another RCT in patients with obesity did not observe significant improvements in PASI and DLQI scores compared to placebo after 8 weeks of liraglutide (initial dose of 0.6 mg/d, titrated to 1.8 mg/d) treatment. ⁹⁹ Although these results could have been influenced by the short length of treatment compared to other studies, which observed participants for more than 10 weeks, they highlight the need for tailored studies considering the different comorbidities to identify patients who could benefit the most from these therapies.

Alopecia—Although some studies have reported increased rates of alopecia following GLP-1 agonist treatment, others have speculated about the potential role of these medications in treating hair loss through improved insulin sensitivity and scalp blood flow.^86,89 For example, a case report described a patient with improvement in androgenetic alopecia within 6 months of tirzepatide monotherapy at 2.5 mg weekly for the first 3 months followed by an increased dose of 5 mg weekly.¹⁰¹ The authors described the role of insulin in increasing dihydrotestosterone levels, which leads to miniaturization of the dermal papilla of hair follicles and argued that improvement of insulin resistance could benefit hair loss. Further studies can help elucidate the role of these medications on alopecia.

FINAL THOUGHTS

Standard T2DM treatments including metformin and GLP-1 and GLP-1/GIP agonists exhibit metabolic, immunologic, and hormonal effects that should be explored in other disease contexts. We reviewed the current data on T2DM medications in dermatologic conditions to highlight the need for additional studies to better understand the role that these medications play across diverse patient populations. Type 2 diabetes mellitus is a common comorbidity in dermatology patients, and understanding the multifactorial effects of these medications can help optimize treatment strategies, especially in patients with coexisting dermatologic and metabolic diseases.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by uncontrolled hyperglycemia. Over the past few decades, its prevalence has steadily increased, now affecting approximately 10% of adults worldwide and ranking among the top 10 leading causes of death globally.¹ The pathophysiology of T2DM involves persistent hyperglycemia that drives insulin resistance and a progressive decline in insulin production from the pancreas.² Medical management of this condition aims to reduce blood glucose levels or enhance insulin production and sensitivity. Aside from lifestyle modifications, metformin is considered the first-line treatment for glycemic control according to the 2023 American Association of Clinical Endocrinology’s T2DM management algorithm.³ These updated guidelines stratify adjunct treatments by individualized glycemic targets and patient needs. For patients who are overweight or obese, glucagonlike peptide 1 (GLP-1) and dual GLP-1/ gastric inhibitory polypeptide (GIP) agonists are the preferred adjunct or second-line treatments.³

In this review, we highlight the dermatologic adverse effects and potential therapeutic benefits of metformin as well as GLP-1 and GLP-1/GIP agonists.

METFORMIN

Metformin is a biguanide agent used as a first-line treatment for T2DM because of its ability to reduce hepatic glucose production and increase peripheral tissue glucose uptake.⁴ In addition to its effects on glucose, metformin has been shown to have anti-inflammatory properties via inhibition of the nuclear factor κB and mammalian target of rapamycin (mTOR) pathways, leading to decreased production of cytokines associated with T helper (Th) 1 and Th17 cell responses, such as IL-17, interferon gamma (IFN-γ), and tumor necrosis factor α (TNF-α).^5-7 These findings have spurred interest among clinicians in the potential use of metformin for inflammatory conditions, including dermatologic diseases such as psoriasis and hidradenitis suppurativa (HS).⁸

Adverse Effects

Metformin is administered orally and generally is well tolerated. The most common adverse effects include gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain.⁹ While cutaneous adverse effects are rare, multiple dermatologic adverse reactions to metformin have been reported,^10,11 including leukocytoclastic vasculitis,^11-13 fixed drug eruptions,^14-17 drug rash with eosinophilia and systemic symptoms (DRESS) syndrome,¹⁸ and photosensitivity reactions.¹⁹ Leukocytoclastic vasculitis and DRESS syndrome typically develop within the first month following metformin initiation, while fixed drug eruption and photosensitivity reactions have more variable timing, occurring weeks to years after treatment initiation.^12-19

Dermatologic Implications

Acanthosis Nigricans—Acanthosis nigricans (AN) is characterized by hyperpigmentation and velvety skin thickening, typically in intertriginous areas such as the back of the neck, axillae, and groin.²⁰ It commonly is associated with insulin resistance and obesity.^21-23 Treatments for AN primarily center around insulin sensitivity and weight loss,^24,25 with some benefit observed from the use of keratolytic agents.^26,27 Metformin may have utility in treating AN through its effects on insulin sensitivity and glycemic control. Multiple case reports have noted marked improvements in AN in patients with and without obesity with the addition of metformin to their existing treatment regimens in doses ranging from 500 mg to 1700 mg daily.^28-30 However, an unblinded randomized controlled trial (RCT) comparing the efficacy of metformin (500 mg 3 times daily) with rosiglitazone (4 mg/d), another T2DM medication, on AN neck lesions in patients who were overweight and obese found no significant effects in lesion severity and only modest improvements in skin texture in both groups at 12 weeks following treatment initiation.³¹ Another RCT comparing metformin (500 mg twice daily) with a twice-daily capsule containing α-lipoic acid, biotin, chromium polynicotinate, and zinc sulfate, showed significant (P<.001) improvements in AN neck lesions in both groups after 12 weeks.³² According to Sung et al,⁸ longer duration of therapy (>6 months), higher doses (1700–2000 mg), and lower baseline weight were associated with higher efficacy of metformin for treatment of AN. Overall, the use of metformin as an adjunct treatment for AN, particularly in patients with underlying hyperglycemia, is supported in the literature, but further studies are needed to clarify dosing, duration of therapy, and patient populations that will benefit most from adding metformin to their treatment regimens.

Hirsutism—Hirsutism, which is characterized by excessive hair growth in androgen-dependent areas, can be challenging to treat. Metformin has been shown to reduce circulating insulin, luteinizing hormone, androstenedione, and testosterone, thus improving underlying hyperandrogenism, particularly in patients with polycystic ovary syndrome (PCOS).^33-35 Although single studies evaluating the efficacy of metformin for treatment of hirsutism in patients with PCOS have shown potential benefits,^36-38 meta-analyses showed no significant effects of metformin compared to placebo or oral contraceptives and decreased benefits compared to spironolactone and flutamide.³⁹ Given these findings showing that metformin was no more effective than placebo or other treatments, the current Endocrine Society guidelines recommend against the use of metformin for hirsutism.^39,40 There may be a role for metformin as an adjuvant therapy in certain populations (eg, patients with comorbid T2DM), although further studies stratifying risk factors such as body mass index and age are needed.⁴¹

Hidradenitis Suppurativa—Hidradenitis suppurativa is a follicular occlusive disease characterized by recurrent inflamed nodules leading to chronic dermal abscesses, fibrosis, and sinus tract formation primarily in intertriginous areas such as the axillae and groin.⁴² Medical management depends on disease severity but usually involves antibiotic treatment with adjunct therapies such as oral contraceptives, antiandrogenic medications (eg, spironolactone), biologic medications, and metformin.⁴² Preclinical and clinical data suggest that metformin can impact HS through metabolic and immunomodulatory mechanisms.^5,42 Like many chronic inflammatory disorders, HS is associated with metabolic syndrome.^43,44 A study evaluating insulin secretion after oral glucose tolerance testing showed increased insulin levels in patients with HS compared to controls (P=.02), with 60% (6/10) of patients with HS meeting criteria for insulin resistance. In addition, serum insulin levels in insulin-resistant patients with HS correlated with increased lesional skin mTOR gene expression at 30 (r=.80) and 60 (r=1.00) minutes, and mTOR was found to be upregulated in lesional and extralesional skin in patients with HS compared to healthy controls (P<.01).45 Insulin activates mTOR signaling, which mediates cell growth and survival, among other processes.⁴⁶ Thus, metformin’s ability to increase insulin sensitivity and inhibit mTOR signaling could be beneficial in the setting of HS. Additionally, insulin and insulinlike growth factor 1 (IGF-1) increase androgen signaling, a process that has been implicated in HS.⁴⁷

Metformin also may impact HS through its effects on testosterone and other hormones.⁴⁸ A study evaluating peripheral blood mononuclear cells in patients with HS showed reduced IL-17, IFN-γ, TNF-α, and IL-6 levels in patients who were taking metformin (dose not reported) for longer than 6 months compared to patients who were not on metformin. Further analysis of ex vivo HS lesions cultured with metformin showed decreased IL-17, IFN-γ, TNF-α, and IL-8 expression in tissue, suggesting an antiinflammatory role of metformin in HS.⁵

Although there are no known RCTs assessing the efficacy of metformin in HS, existing clinical data are supportive of the use of metformin for refractory HS.⁴⁹ Following a case report describing a patient with T2DM and stable HS while on metformin,⁵⁰ several cohort studies have assessed the efficacy of metformin for the treatment of HS. A prospective study evaluating the efficacy of metformin monotherapy (starting dose of 500 mg/d, titrated to 500 mg 3 times daily) in patients with and without T2DM with HS refractory to other therapies found clinical improvement in 72% (18/25) of patients using the Sartorius Hidradenitis Suppurativa Score, improving from a mean (SD) score of 34.40 (12.46) to 26.76 (11.22) at 12 weeks (P=.0055,) and 22.39 (11.30) at 24 weeks (P=.0001). Additionally, 64% (16/25) of patients showed improved quality of life as evaluated by the Dermatology Life Quality Index (DLQI), which decreased from a mean (SD) score of 15.00 (4.96) to 10.08 (5.96)(P=.0017) at 12 weeks and 7.65 (7.12)(P=.000009) at 24 weeks on treatment.⁴⁸ In a retrospective study of 53 patients with HS taking metformin started at 500 mg daily and increased to 500 mg twice daily after 2 weeks (when tolerated), 68% (36/53) showed some clinical response, with 19% (7/36) of those patients having achieved complete response to metformin monotherapy (defined as no active HS).⁵¹ Similarly, a retrospective study of pediatric patients with HS evaluating metformin (doses ranging from 500-2000 mg daily) as an adjunct therapy described a subset of patients with decreased frequency of HS flares with metformin.⁵² These studies emphasize the safety profile of metformin and support its current use as an adjunctive therapy for HS.

Acne Vulgaris—Acne vulgaris (AV) is a chronic inflammatory disorder affecting the pilosebaceous follicles.¹¹ Similar to HS, AV has metabolic and hormonal influences that can be targeted by metformin.⁵³ In AV, androgens lead to increased sebum production by binding to androgen receptors on sebocytes, which in turn attracts Cutibacterium acnes and promotes hyperkeratinization, inducing inflammation.⁵⁴ Thus, the antiandrogenic effects of metformin may be beneficial for treatment of AV. Additionally, sebocytes express receptors for insulin and IGF-1, which can increase the size and number of sebocytes, as well as promote lipogenesis and inflammatory response, influencing sebum production.⁵⁴ Serum levels for IGF-1 have been observed to be increased in patients with AV⁵⁵ and reduced by metformin.⁵⁶ A recent meta-analysis assessing the efficacy of metformin on AV indicated that 87% (13/15) of studies noted disease improvement on metformin, with 47% (7/15) of studies showing statistically significant (P<0.05) decreases in acne severity.57 Although most studies showed improvement, 47% (7/15) did not find significant differences between metformin and other interventions, indicating the availability of comparable treatment options. Overall, there has been a positive association between metformin use and acne improvement.⁵⁷ However, it is important to note that most studies have focused on females with PCOS,⁵⁷ and the main benefits of metformin in acne might be seen when managing comorbid conditions, particularly those associated with metabolic dysregulation and insulin resistance. Further studies are needed to determine the generalizability of prior results.

Psoriasis—Psoriasis is a chronic autoinflammatory disease characterized by epidermal hyperplasia with multiple cutaneous manifestations and potential for multiorgan involvement. Comorbid conditions include psoriatic arthritis, metabolic syndrome, and cardiovascular disease.⁵⁸ Current treatment options depend on several factors (eg, disease severity, location of cutaneous lesions, comorbidities) and include topical, systemic, and phototherapy options, many of which target the immune system.^58,59 A meta-analysis of 3 RCTs showed that metformin (500 mg/d or 1000 mg/d) was associated with significantly improved Psoriasis Area and Severity Index (PASI) 75% reductions (odds ratio [OR], 22.02; 95% CI, 2.12-228.49; P=.01) and 75% reductions in erythema, scaling, and induration (OR, 9.12; 95% CI, 2.13-39.02; P=.003) compared to placebo.⁶⁰ In addition, an RCT evaluating the efficacy of metformin (1000 mg/d) or pioglitazone (30 mg/d) for 12 weeks in patients with psoriasis with metabolic syndrome found significant improvements in PASI75 (P=.001) and erythema, scaling, and induration (P=.016) scores as well as in Physician Global Assessment scores (P=.012) compared to placebo and no differences compared to pioglitazone.⁶¹ While current psoriasis management guidelines do not include metformin, its use may be worth consideration as an adjunct therapy in patients with psoriasis and comorbidities such as T2DM and metabolic syndrome.⁵⁹ Metformin’s potential benefits in psoriasis may lie outside its metabolic influences and occur secondary to its immunomodulatory effects, including targeting of the Th17 axis or cytokine-specific pathways such as TNF-α, which are known to be involved in psoriasis pathogenesis.⁵⁸

Central Centrifugal Cicatricial Alopecia—Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia characterized by chronic inflammation leading to permanent loss of hair follicles on the crown of the scalp.⁶² Current treatments include topical and intralesional corticosteroids, as well as oral antibiotics. In addition, therapies including the antimalarial hydroxychloroquine and immunosuppressants mycophenolate and cyclosporine are used in refractory disease.^63,64 A case report described 2 patients with hair regrowth after 4 and 6 months of treatment with topical metformin 10% compounded in a proprietary transdermal vehicle.⁶⁵ The authors speculated that metformin’s effects on CCCA could be attributed to its known agonistic effects on the adenosine monophosphate-activated protein kinase (AMPK) pathway with subsequent reduction in inflammation-induced fibrosis.^65,66 Microarray⁶⁷ and proteomic⁶⁸ analysis have shown that AMPK is known to be downregulated in CCCA , making it an interesting therapeutic target in this disease. A recent retrospective case series demonstrated that 67% (8/12) of patients with refractory CCCA had symptomatic improvement, and 50% (6/12) showed hair regrowth after 6 months of low-dose (500 mg/d) oral metformin treatment.⁶² In addition, metformin therapy showed antifibrotic and anti-inflammatory effects when comparing scalp biopsies before and after treatment. Results showed decreased expression of fibrosisrelated genes (matrix metalloproteinase 7, collagen type IV á 1 chain), and gene set variation analysis showing reduced Th17 (P=.04) and increased AMPK signaling (P=.02) gene set expression.⁶² These findings are consistent with previous studies describing the upregulation of AMPK66 and downregulation of Th176 following metformin treatment. The immunomodulatory effects of metformin could be attributed to AMPK-mediated mTOR and NF-κB downregulation,⁶² although more studies are needed to understand these mechanisms and further explore the use of metformin in CCCA.

Skin Cancer—Metformin also has been evaluated in the setting of skin malignancies, including melanoma, squamous cell carcinoma, and basal cell carcinoma. Preclinical data suggest that metformin decreases cell viability in tumors through interactions with pathways involved in proinflammatory and prosurvival mechanisms such as NF-κB and mTOR.^69,70 Additionally, given metformin’s inhibitory effects on oxidative phosphorylation, it has been postulated that it could be used to overcome treatment resistance driven by metabolic reprogramming.^71,72 Most studies related to metformin and skin malignancies are still in preclinical stages; however, a meta-analysis of RCTs and cohort studies did not find significant associations between metformin use and skin cancer risk, although data trended toward a modest reduction in skin cancer among metformin users.⁷³ A retrospective cohort study of melanoma in patients with T2DM taking metformin (250-2000 mg/d) found that the 5-year incidence of recurrence was lower in the metformin cohort compared to nonusers (43.8% vs 58.2%, respectively)(P=.002), and overall survival rates trended upward in the higher body mass index (>30) and melanoma stages 1 and 2 groups but did not reach statistical significance.⁷⁴ In addition, a whole population casecontrol study in Iceland reported that metformin use at least 2 years before first-time basal cell carcinoma diagnosis was associated with a lower risk for disease (adjusted OR, 0.71; 95% CI, 0.61-0.83) with no significant dose-dependent differences; there were no notable effects on squamous cell carcinoma risk.⁷⁵ Further preclinical and clinical data are needed to elucidate metformin’s effects on skin malignancies.

GLP-1 AND DUAL GLP-1/GIP AGONISTS

Glucagonlike peptide 1 and dual GLP-1/GIP agonists are emerging classes of medications currently approved as adjunct and second-line therapies for T2DM, particularly in patients who are overweight or obese as well as in those who are at risk for hypoglycemia.³ Currently approved GLP-1 agonists for T2DM include semaglutide, dulaglutide, exenatide, liraglutide, and lixisenatide, while tirzepatide is the only approved dual GLP-1/GIP agonist. Activating GLP-1 and GIP receptors stimulates insulin secretion and decreases glucagon production by the pancreas, thereby reducing blood glucose levels. Additionally, some of these medications are approved for obesity given their effects in delayed gastric emptying and increased satiety, among other factors.

Over the past few years, multiple case reports have described the associations between GLP-1 agonist use and improvement of dermatologic conditions, particularly those associated with T2DM and obesity, including HS and psoriasis.^76,77 The mechanisms through which this occurs are not fully elucidated, although basic science and clinical studies have shown that GLP-1 agonists have immunomodulatory effects by reducing proinflammatory cytokines and altering immune cell populations.^77-80 The numerous ongoing clinical trials and research studies will help further elucidate their benefits in other disease settings.⁸¹

Adverse Reactions

Most GLP-1 and GLP-1/GIP agonists are administered subcutaneously, and the most commonly reported cutaneous adverse effects are injection site reactions.⁸² Anaphylactic reactions to these medications also have been reported, although it is unclear if these were specific to the active ingredients or to injection excipients.^83,84 A review of 33 cases of cutaneous reactions to GLP-1 agonists reported 11 (33%) dermal hypersensitivity reactions occurring as early as 4 weeks and as late as 3 years after treatment initiation. It also described 10 (30%) cases of eosinophilic panniculitis that developed within 3 weeks to 5 months of GLP-1 treatment, 3 (9%) cases of bullous pemphigoid that occurred within the first 2 months, 2 (6%) morbilliform drug eruptions that occurred within 5 weeks, 2 (6%) cases of angioedema that occurred 15 minutes to 2 weeks after treatment initiation, and 7 (21%) other isolated cutaneous reactions. Extended-release exenatide had the most reported reactions followed by liraglutide and subcutaneous semaglutide.⁸⁵

In a different study, semaglutide use was most commonly associated with injection site reactions followed by alopecia, especially with oral administration. Unique cases of angioedema (2 days after injection), cutaneous hypersensitivity (within 10 months on treatment), bullous pemphigoid (within 2 months on treatment), eosinophilic fasciitis (within 2 weeks on treatment), and leukocytoclastic vasculitis (unclear timing), most of which resolved after discontinuation, also were reported.⁸⁶ A recent case report linked semaglutide (0.5 mg/wk) to a case of drug-induced systemic lupus erythematosus that developed within 3 months of treatment initiation and described systemic lupus erythematosus–like symptoms in a subset of patients using this medication, namely females older than 60 years, within the first month of treatment.⁸⁷ Hyperhidrosis was listed as a common adverse event in exenatide clinical trials, and various cases of panniculitis with exenatide use have been reported.^82,88 Alopecia, mainly attributed to accelerated telogen effluvium secondary to rapid weight loss, also has been reported, although hair loss is not officially listed as an adverse effect of GLP-1 agonists, and reports are highly variable.⁸⁹ Also secondary to weight loss, facial changes including sunken eyes, development of wrinkles, sagging jowls around the neck and jaw, and a hollowed appearance, among others, are recognized as undesirable adverse effects.⁹⁰ Mansour et al⁹⁰ described the potential challenges and considerations to these rising concerns associated with GLP1-agonist use.

Dermatologic Implications

Hidradenitis Suppurativa—Weight loss commonly is recommended as a lifestyle modification in the management of HS. Multiple reports have described clinical improvement of HS following weight loss with other medical interventions, such as dietary measures and bariatric surgery.^91-94 Thus, it has been postulated that medically supported weight loss with GLP-1 agonists can help improve HS⁹⁵; however, the data on the effectiveness of GLP-1 agonists on HS are still scarce and mostly have been reported in individual patients. One case report described a patient with improvements in their recalcitrant HS and DLQI score following weight loss on liraglutide (initial dose of 0.6 mg/d, titrated to 1.8 mg/d).⁷⁶ In addition, a recent case report described improvements in HS and DLQI score following concomitant tirzepatide (initial dose of 2.5 mg/0.5 mL weekly, titrated to 7.5 mg/0.5 mL weekly) and infliximab treatment.⁹⁶ The off-label use of these medications for HS is debated, and further studies regarding the benefits of GLP-1 agonists on HS still are needed.

Psoriasis—Similarly, several case reports have commented on the effects of GLP-1 agonists on psoriasis.^97,98 An early study found GLP-1 receptors were expressed in psoriasis plaques but not in healthy skin and discussed that this could be due to immune infiltration in the plaques, providing a potential rationale for using anti-inflammatory GLP-1 agonists for psoriasis.⁹⁹ Two prospective cohort studies observed improvements in PASI and DLQI scores in patients with psoriasis and T2DM after liraglutide treatment and noted important changes in immune cell populations.^80,100 A recent RCT also found improvements in DLQI and PASI scores (P<.05) in patients with T2DM following liraglutide (1.8 mg/d) treatment, along with overall decreases in inflammatory cytokines, such as IL-23, IL-17, and TNF-α.⁷⁷ However, another RCT in patients with obesity did not observe significant improvements in PASI and DLQI scores compared to placebo after 8 weeks of liraglutide (initial dose of 0.6 mg/d, titrated to 1.8 mg/d) treatment. ⁹⁹ Although these results could have been influenced by the short length of treatment compared to other studies, which observed participants for more than 10 weeks, they highlight the need for tailored studies considering the different comorbidities to identify patients who could benefit the most from these therapies.

Alopecia—Although some studies have reported increased rates of alopecia following GLP-1 agonist treatment, others have speculated about the potential role of these medications in treating hair loss through improved insulin sensitivity and scalp blood flow.^86,89 For example, a case report described a patient with improvement in androgenetic alopecia within 6 months of tirzepatide monotherapy at 2.5 mg weekly for the first 3 months followed by an increased dose of 5 mg weekly.¹⁰¹ The authors described the role of insulin in increasing dihydrotestosterone levels, which leads to miniaturization of the dermal papilla of hair follicles and argued that improvement of insulin resistance could benefit hair loss. Further studies can help elucidate the role of these medications on alopecia.

FINAL THOUGHTS

Standard T2DM treatments including metformin and GLP-1 and GLP-1/GIP agonists exhibit metabolic, immunologic, and hormonal effects that should be explored in other disease contexts. We reviewed the current data on T2DM medications in dermatologic conditions to highlight the need for additional studies to better understand the role that these medications play across diverse patient populations. Type 2 diabetes mellitus is a common comorbidity in dermatology patients, and understanding the multifactorial effects of these medications can help optimize treatment strategies, especially in patients with coexisting dermatologic and metabolic diseases.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by uncontrolled hyperglycemia. Over the past few decades, its prevalence has steadily increased, now affecting approximately 10% of adults worldwide and ranking among the top 10 leading causes of death globally.¹ The pathophysiology of T2DM involves persistent hyperglycemia that drives insulin resistance and a progressive decline in insulin production from the pancreas.² Medical management of this condition aims to reduce blood glucose levels or enhance insulin production and sensitivity. Aside from lifestyle modifications, metformin is considered the first-line treatment for glycemic control according to the 2023 American Association of Clinical Endocrinology’s T2DM management algorithm.³ These updated guidelines stratify adjunct treatments by individualized glycemic targets and patient needs. For patients who are overweight or obese, glucagonlike peptide 1 (GLP-1) and dual GLP-1/ gastric inhibitory polypeptide (GIP) agonists are the preferred adjunct or second-line treatments.³

In this review, we highlight the dermatologic adverse effects and potential therapeutic benefits of metformin as well as GLP-1 and GLP-1/GIP agonists.

METFORMIN

Metformin is a biguanide agent used as a first-line treatment for T2DM because of its ability to reduce hepatic glucose production and increase peripheral tissue glucose uptake.⁴ In addition to its effects on glucose, metformin has been shown to have anti-inflammatory properties via inhibition of the nuclear factor κB and mammalian target of rapamycin (mTOR) pathways, leading to decreased production of cytokines associated with T helper (Th) 1 and Th17 cell responses, such as IL-17, interferon gamma (IFN-γ), and tumor necrosis factor α (TNF-α).^5-7 These findings have spurred interest among clinicians in the potential use of metformin for inflammatory conditions, including dermatologic diseases such as psoriasis and hidradenitis suppurativa (HS).⁸

Adverse Effects

Metformin is administered orally and generally is well tolerated. The most common adverse effects include gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain.⁹ While cutaneous adverse effects are rare, multiple dermatologic adverse reactions to metformin have been reported,^10,11 including leukocytoclastic vasculitis,^11-13 fixed drug eruptions,^14-17 drug rash with eosinophilia and systemic symptoms (DRESS) syndrome,¹⁸ and photosensitivity reactions.¹⁹ Leukocytoclastic vasculitis and DRESS syndrome typically develop within the first month following metformin initiation, while fixed drug eruption and photosensitivity reactions have more variable timing, occurring weeks to years after treatment initiation.^12-19

Dermatologic Implications

Acanthosis Nigricans—Acanthosis nigricans (AN) is characterized by hyperpigmentation and velvety skin thickening, typically in intertriginous areas such as the back of the neck, axillae, and groin.²⁰ It commonly is associated with insulin resistance and obesity.^21-23 Treatments for AN primarily center around insulin sensitivity and weight loss,^24,25 with some benefit observed from the use of keratolytic agents.^26,27 Metformin may have utility in treating AN through its effects on insulin sensitivity and glycemic control. Multiple case reports have noted marked improvements in AN in patients with and without obesity with the addition of metformin to their existing treatment regimens in doses ranging from 500 mg to 1700 mg daily.^28-30 However, an unblinded randomized controlled trial (RCT) comparing the efficacy of metformin (500 mg 3 times daily) with rosiglitazone (4 mg/d), another T2DM medication, on AN neck lesions in patients who were overweight and obese found no significant effects in lesion severity and only modest improvements in skin texture in both groups at 12 weeks following treatment initiation.³¹ Another RCT comparing metformin (500 mg twice daily) with a twice-daily capsule containing α-lipoic acid, biotin, chromium polynicotinate, and zinc sulfate, showed significant (P<.001) improvements in AN neck lesions in both groups after 12 weeks.³² According to Sung et al,⁸ longer duration of therapy (>6 months), higher doses (1700–2000 mg), and lower baseline weight were associated with higher efficacy of metformin for treatment of AN. Overall, the use of metformin as an adjunct treatment for AN, particularly in patients with underlying hyperglycemia, is supported in the literature, but further studies are needed to clarify dosing, duration of therapy, and patient populations that will benefit most from adding metformin to their treatment regimens.

Hirsutism—Hirsutism, which is characterized by excessive hair growth in androgen-dependent areas, can be challenging to treat. Metformin has been shown to reduce circulating insulin, luteinizing hormone, androstenedione, and testosterone, thus improving underlying hyperandrogenism, particularly in patients with polycystic ovary syndrome (PCOS).^33-35 Although single studies evaluating the efficacy of metformin for treatment of hirsutism in patients with PCOS have shown potential benefits,^36-38 meta-analyses showed no significant effects of metformin compared to placebo or oral contraceptives and decreased benefits compared to spironolactone and flutamide.³⁹ Given these findings showing that metformin was no more effective than placebo or other treatments, the current Endocrine Society guidelines recommend against the use of metformin for hirsutism.^39,40 There may be a role for metformin as an adjuvant therapy in certain populations (eg, patients with comorbid T2DM), although further studies stratifying risk factors such as body mass index and age are needed.⁴¹

Hidradenitis Suppurativa—Hidradenitis suppurativa is a follicular occlusive disease characterized by recurrent inflamed nodules leading to chronic dermal abscesses, fibrosis, and sinus tract formation primarily in intertriginous areas such as the axillae and groin.⁴² Medical management depends on disease severity but usually involves antibiotic treatment with adjunct therapies such as oral contraceptives, antiandrogenic medications (eg, spironolactone), biologic medications, and metformin.⁴² Preclinical and clinical data suggest that metformin can impact HS through metabolic and immunomodulatory mechanisms.^5,42 Like many chronic inflammatory disorders, HS is associated with metabolic syndrome.^43,44 A study evaluating insulin secretion after oral glucose tolerance testing showed increased insulin levels in patients with HS compared to controls (P=.02), with 60% (6/10) of patients with HS meeting criteria for insulin resistance. In addition, serum insulin levels in insulin-resistant patients with HS correlated with increased lesional skin mTOR gene expression at 30 (r=.80) and 60 (r=1.00) minutes, and mTOR was found to be upregulated in lesional and extralesional skin in patients with HS compared to healthy controls (P<.01).45 Insulin activates mTOR signaling, which mediates cell growth and survival, among other processes.⁴⁶ Thus, metformin’s ability to increase insulin sensitivity and inhibit mTOR signaling could be beneficial in the setting of HS. Additionally, insulin and insulinlike growth factor 1 (IGF-1) increase androgen signaling, a process that has been implicated in HS.⁴⁷

Metformin also may impact HS through its effects on testosterone and other hormones.⁴⁸ A study evaluating peripheral blood mononuclear cells in patients with HS showed reduced IL-17, IFN-γ, TNF-α, and IL-6 levels in patients who were taking metformin (dose not reported) for longer than 6 months compared to patients who were not on metformin. Further analysis of ex vivo HS lesions cultured with metformin showed decreased IL-17, IFN-γ, TNF-α, and IL-8 expression in tissue, suggesting an antiinflammatory role of metformin in HS.⁵

Although there are no known RCTs assessing the efficacy of metformin in HS, existing clinical data are supportive of the use of metformin for refractory HS.⁴⁹ Following a case report describing a patient with T2DM and stable HS while on metformin,⁵⁰ several cohort studies have assessed the efficacy of metformin for the treatment of HS. A prospective study evaluating the efficacy of metformin monotherapy (starting dose of 500 mg/d, titrated to 500 mg 3 times daily) in patients with and without T2DM with HS refractory to other therapies found clinical improvement in 72% (18/25) of patients using the Sartorius Hidradenitis Suppurativa Score, improving from a mean (SD) score of 34.40 (12.46) to 26.76 (11.22) at 12 weeks (P=.0055,) and 22.39 (11.30) at 24 weeks (P=.0001). Additionally, 64% (16/25) of patients showed improved quality of life as evaluated by the Dermatology Life Quality Index (DLQI), which decreased from a mean (SD) score of 15.00 (4.96) to 10.08 (5.96)(P=.0017) at 12 weeks and 7.65 (7.12)(P=.000009) at 24 weeks on treatment.⁴⁸ In a retrospective study of 53 patients with HS taking metformin started at 500 mg daily and increased to 500 mg twice daily after 2 weeks (when tolerated), 68% (36/53) showed some clinical response, with 19% (7/36) of those patients having achieved complete response to metformin monotherapy (defined as no active HS).⁵¹ Similarly, a retrospective study of pediatric patients with HS evaluating metformin (doses ranging from 500-2000 mg daily) as an adjunct therapy described a subset of patients with decreased frequency of HS flares with metformin.⁵² These studies emphasize the safety profile of metformin and support its current use as an adjunctive therapy for HS.

Acne Vulgaris—Acne vulgaris (AV) is a chronic inflammatory disorder affecting the pilosebaceous follicles.¹¹ Similar to HS, AV has metabolic and hormonal influences that can be targeted by metformin.⁵³ In AV, androgens lead to increased sebum production by binding to androgen receptors on sebocytes, which in turn attracts Cutibacterium acnes and promotes hyperkeratinization, inducing inflammation.⁵⁴ Thus, the antiandrogenic effects of metformin may be beneficial for treatment of AV. Additionally, sebocytes express receptors for insulin and IGF-1, which can increase the size and number of sebocytes, as well as promote lipogenesis and inflammatory response, influencing sebum production.⁵⁴ Serum levels for IGF-1 have been observed to be increased in patients with AV⁵⁵ and reduced by metformin.⁵⁶ A recent meta-analysis assessing the efficacy of metformin on AV indicated that 87% (13/15) of studies noted disease improvement on metformin, with 47% (7/15) of studies showing statistically significant (P<0.05) decreases in acne severity.57 Although most studies showed improvement, 47% (7/15) did not find significant differences between metformin and other interventions, indicating the availability of comparable treatment options. Overall, there has been a positive association between metformin use and acne improvement.⁵⁷ However, it is important to note that most studies have focused on females with PCOS,⁵⁷ and the main benefits of metformin in acne might be seen when managing comorbid conditions, particularly those associated with metabolic dysregulation and insulin resistance. Further studies are needed to determine the generalizability of prior results.

Psoriasis—Psoriasis is a chronic autoinflammatory disease characterized by epidermal hyperplasia with multiple cutaneous manifestations and potential for multiorgan involvement. Comorbid conditions include psoriatic arthritis, metabolic syndrome, and cardiovascular disease.⁵⁸ Current treatment options depend on several factors (eg, disease severity, location of cutaneous lesions, comorbidities) and include topical, systemic, and phototherapy options, many of which target the immune system.^58,59 A meta-analysis of 3 RCTs showed that metformin (500 mg/d or 1000 mg/d) was associated with significantly improved Psoriasis Area and Severity Index (PASI) 75% reductions (odds ratio [OR], 22.02; 95% CI, 2.12-228.49; P=.01) and 75% reductions in erythema, scaling, and induration (OR, 9.12; 95% CI, 2.13-39.02; P=.003) compared to placebo.⁶⁰ In addition, an RCT evaluating the efficacy of metformin (1000 mg/d) or pioglitazone (30 mg/d) for 12 weeks in patients with psoriasis with metabolic syndrome found significant improvements in PASI75 (P=.001) and erythema, scaling, and induration (P=.016) scores as well as in Physician Global Assessment scores (P=.012) compared to placebo and no differences compared to pioglitazone.⁶¹ While current psoriasis management guidelines do not include metformin, its use may be worth consideration as an adjunct therapy in patients with psoriasis and comorbidities such as T2DM and metabolic syndrome.⁵⁹ Metformin’s potential benefits in psoriasis may lie outside its metabolic influences and occur secondary to its immunomodulatory effects, including targeting of the Th17 axis or cytokine-specific pathways such as TNF-α, which are known to be involved in psoriasis pathogenesis.⁵⁸

Central Centrifugal Cicatricial Alopecia—Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia characterized by chronic inflammation leading to permanent loss of hair follicles on the crown of the scalp.⁶² Current treatments include topical and intralesional corticosteroids, as well as oral antibiotics. In addition, therapies including the antimalarial hydroxychloroquine and immunosuppressants mycophenolate and cyclosporine are used in refractory disease.^63,64 A case report described 2 patients with hair regrowth after 4 and 6 months of treatment with topical metformin 10% compounded in a proprietary transdermal vehicle.⁶⁵ The authors speculated that metformin’s effects on CCCA could be attributed to its known agonistic effects on the adenosine monophosphate-activated protein kinase (AMPK) pathway with subsequent reduction in inflammation-induced fibrosis.^65,66 Microarray⁶⁷ and proteomic⁶⁸ analysis have shown that AMPK is known to be downregulated in CCCA , making it an interesting therapeutic target in this disease. A recent retrospective case series demonstrated that 67% (8/12) of patients with refractory CCCA had symptomatic improvement, and 50% (6/12) showed hair regrowth after 6 months of low-dose (500 mg/d) oral metformin treatment.⁶² In addition, metformin therapy showed antifibrotic and anti-inflammatory effects when comparing scalp biopsies before and after treatment. Results showed decreased expression of fibrosisrelated genes (matrix metalloproteinase 7, collagen type IV á 1 chain), and gene set variation analysis showing reduced Th17 (P=.04) and increased AMPK signaling (P=.02) gene set expression.⁶² These findings are consistent with previous studies describing the upregulation of AMPK66 and downregulation of Th176 following metformin treatment. The immunomodulatory effects of metformin could be attributed to AMPK-mediated mTOR and NF-κB downregulation,⁶² although more studies are needed to understand these mechanisms and further explore the use of metformin in CCCA.

Skin Cancer—Metformin also has been evaluated in the setting of skin malignancies, including melanoma, squamous cell carcinoma, and basal cell carcinoma. Preclinical data suggest that metformin decreases cell viability in tumors through interactions with pathways involved in proinflammatory and prosurvival mechanisms such as NF-κB and mTOR.^69,70 Additionally, given metformin’s inhibitory effects on oxidative phosphorylation, it has been postulated that it could be used to overcome treatment resistance driven by metabolic reprogramming.^71,72 Most studies related to metformin and skin malignancies are still in preclinical stages; however, a meta-analysis of RCTs and cohort studies did not find significant associations between metformin use and skin cancer risk, although data trended toward a modest reduction in skin cancer among metformin users.⁷³ A retrospective cohort study of melanoma in patients with T2DM taking metformin (250-2000 mg/d) found that the 5-year incidence of recurrence was lower in the metformin cohort compared to nonusers (43.8% vs 58.2%, respectively)(P=.002), and overall survival rates trended upward in the higher body mass index (>30) and melanoma stages 1 and 2 groups but did not reach statistical significance.⁷⁴ In addition, a whole population casecontrol study in Iceland reported that metformin use at least 2 years before first-time basal cell carcinoma diagnosis was associated with a lower risk for disease (adjusted OR, 0.71; 95% CI, 0.61-0.83) with no significant dose-dependent differences; there were no notable effects on squamous cell carcinoma risk.⁷⁵ Further preclinical and clinical data are needed to elucidate metformin’s effects on skin malignancies.

GLP-1 AND DUAL GLP-1/GIP AGONISTS

Glucagonlike peptide 1 and dual GLP-1/GIP agonists are emerging classes of medications currently approved as adjunct and second-line therapies for T2DM, particularly in patients who are overweight or obese as well as in those who are at risk for hypoglycemia.³ Currently approved GLP-1 agonists for T2DM include semaglutide, dulaglutide, exenatide, liraglutide, and lixisenatide, while tirzepatide is the only approved dual GLP-1/GIP agonist. Activating GLP-1 and GIP receptors stimulates insulin secretion and decreases glucagon production by the pancreas, thereby reducing blood glucose levels. Additionally, some of these medications are approved for obesity given their effects in delayed gastric emptying and increased satiety, among other factors.

Over the past few years, multiple case reports have described the associations between GLP-1 agonist use and improvement of dermatologic conditions, particularly those associated with T2DM and obesity, including HS and psoriasis.^76,77 The mechanisms through which this occurs are not fully elucidated, although basic science and clinical studies have shown that GLP-1 agonists have immunomodulatory effects by reducing proinflammatory cytokines and altering immune cell populations.^77-80 The numerous ongoing clinical trials and research studies will help further elucidate their benefits in other disease settings.⁸¹

Adverse Reactions

Most GLP-1 and GLP-1/GIP agonists are administered subcutaneously, and the most commonly reported cutaneous adverse effects are injection site reactions.⁸² Anaphylactic reactions to these medications also have been reported, although it is unclear if these were specific to the active ingredients or to injection excipients.^83,84 A review of 33 cases of cutaneous reactions to GLP-1 agonists reported 11 (33%) dermal hypersensitivity reactions occurring as early as 4 weeks and as late as 3 years after treatment initiation. It also described 10 (30%) cases of eosinophilic panniculitis that developed within 3 weeks to 5 months of GLP-1 treatment, 3 (9%) cases of bullous pemphigoid that occurred within the first 2 months, 2 (6%) morbilliform drug eruptions that occurred within 5 weeks, 2 (6%) cases of angioedema that occurred 15 minutes to 2 weeks after treatment initiation, and 7 (21%) other isolated cutaneous reactions. Extended-release exenatide had the most reported reactions followed by liraglutide and subcutaneous semaglutide.⁸⁵

In a different study, semaglutide use was most commonly associated with injection site reactions followed by alopecia, especially with oral administration. Unique cases of angioedema (2 days after injection), cutaneous hypersensitivity (within 10 months on treatment), bullous pemphigoid (within 2 months on treatment), eosinophilic fasciitis (within 2 weeks on treatment), and leukocytoclastic vasculitis (unclear timing), most of which resolved after discontinuation, also were reported.⁸⁶ A recent case report linked semaglutide (0.5 mg/wk) to a case of drug-induced systemic lupus erythematosus that developed within 3 months of treatment initiation and described systemic lupus erythematosus–like symptoms in a subset of patients using this medication, namely females older than 60 years, within the first month of treatment.⁸⁷ Hyperhidrosis was listed as a common adverse event in exenatide clinical trials, and various cases of panniculitis with exenatide use have been reported.^82,88 Alopecia, mainly attributed to accelerated telogen effluvium secondary to rapid weight loss, also has been reported, although hair loss is not officially listed as an adverse effect of GLP-1 agonists, and reports are highly variable.⁸⁹ Also secondary to weight loss, facial changes including sunken eyes, development of wrinkles, sagging jowls around the neck and jaw, and a hollowed appearance, among others, are recognized as undesirable adverse effects.⁹⁰ Mansour et al⁹⁰ described the potential challenges and considerations to these rising concerns associated with GLP1-agonist use.

Dermatologic Implications

Hidradenitis Suppurativa—Weight loss commonly is recommended as a lifestyle modification in the management of HS. Multiple reports have described clinical improvement of HS following weight loss with other medical interventions, such as dietary measures and bariatric surgery.^91-94 Thus, it has been postulated that medically supported weight loss with GLP-1 agonists can help improve HS⁹⁵; however, the data on the effectiveness of GLP-1 agonists on HS are still scarce and mostly have been reported in individual patients. One case report described a patient with improvements in their recalcitrant HS and DLQI score following weight loss on liraglutide (initial dose of 0.6 mg/d, titrated to 1.8 mg/d).⁷⁶ In addition, a recent case report described improvements in HS and DLQI score following concomitant tirzepatide (initial dose of 2.5 mg/0.5 mL weekly, titrated to 7.5 mg/0.5 mL weekly) and infliximab treatment.⁹⁶ The off-label use of these medications for HS is debated, and further studies regarding the benefits of GLP-1 agonists on HS still are needed.

Psoriasis—Similarly, several case reports have commented on the effects of GLP-1 agonists on psoriasis.^97,98 An early study found GLP-1 receptors were expressed in psoriasis plaques but not in healthy skin and discussed that this could be due to immune infiltration in the plaques, providing a potential rationale for using anti-inflammatory GLP-1 agonists for psoriasis.⁹⁹ Two prospective cohort studies observed improvements in PASI and DLQI scores in patients with psoriasis and T2DM after liraglutide treatment and noted important changes in immune cell populations.^80,100 A recent RCT also found improvements in DLQI and PASI scores (P<.05) in patients with T2DM following liraglutide (1.8 mg/d) treatment, along with overall decreases in inflammatory cytokines, such as IL-23, IL-17, and TNF-α.⁷⁷ However, another RCT in patients with obesity did not observe significant improvements in PASI and DLQI scores compared to placebo after 8 weeks of liraglutide (initial dose of 0.6 mg/d, titrated to 1.8 mg/d) treatment. ⁹⁹ Although these results could have been influenced by the short length of treatment compared to other studies, which observed participants for more than 10 weeks, they highlight the need for tailored studies considering the different comorbidities to identify patients who could benefit the most from these therapies.

Alopecia—Although some studies have reported increased rates of alopecia following GLP-1 agonist treatment, others have speculated about the potential role of these medications in treating hair loss through improved insulin sensitivity and scalp blood flow.^86,89 For example, a case report described a patient with improvement in androgenetic alopecia within 6 months of tirzepatide monotherapy at 2.5 mg weekly for the first 3 months followed by an increased dose of 5 mg weekly.¹⁰¹ The authors described the role of insulin in increasing dihydrotestosterone levels, which leads to miniaturization of the dermal papilla of hair follicles and argued that improvement of insulin resistance could benefit hair loss. Further studies can help elucidate the role of these medications on alopecia.

FINAL THOUGHTS

Standard T2DM treatments including metformin and GLP-1 and GLP-1/GIP agonists exhibit metabolic, immunologic, and hormonal effects that should be explored in other disease contexts. We reviewed the current data on T2DM medications in dermatologic conditions to highlight the need for additional studies to better understand the role that these medications play across diverse patient populations. Type 2 diabetes mellitus is a common comorbidity in dermatology patients, and understanding the multifactorial effects of these medications can help optimize treatment strategies, especially in patients with coexisting dermatologic and metabolic diseases.

THE DIAGNOSIS: Trichodiscoma

Histologic evaluation revealed an unremarkable epidermal surface and a subjacent well-demarcated superficial dermal nodule showing a proliferation, sometimes fascicular, of wavy and spindled fibroblasts with some stellate forms within a variably loose fibrous stroma. Some angioplasia and vascular ectasia also were seen (Figure). A diagnosis of trichodiscoma was made based on these histologic findings.

While the patient’s personal and family history of pneumothorax originally had been attributed to other causes, the diagnosis of trichodiscoma raised suspicion for Birt-Hogg-Dubé syndrome due to the classic association of skin lesions (often trichodiscomas), renal cell carcinoma, and spontaneous pneumothorax in this condition. The patient was sent for genetic testing for the associated folliculin (FLCN) gene, which was positive and thereby confirmed the diagnosis of Birt-Hogg-Dubé syndrome. At the most recent follow-up almost 2 years after initial presentation, the lesions on the earlobe were stable. The patient has since undergone screening for abdominal and renal neoplasia with negative results, and he has had no other occurrences of pneumothorax.

Our case highlights the association between trichodiscomas and Birt-Hogg-Dubé syndrome, which necessitates screening for renal cell carcinoma, pneumothorax, and lung cysts.¹ Birt-Hogg-Dubé syndrome is an autosomal- dominant disorder of the skin and lungs that is characterized by a predisposition for renal carcinoma, pneumothorax, and colon polyps as well as cutaneous markers that include fibrofolliculomas, acrochordons, and trichodiscomas; the trichodiscomas tend to manifest as numerous smooth, flesh-colored or grayish-white papules on the face, ears, neck, and/or upper trunk.¹

Trichodiscomas are benign lesions and do not require treatment²; however, if they are cosmetically bothersome to the patient, surgical excision is an option for single lesions. For more widespread cutaneous disease, combination therapy with a CO₂ laser and erbium-doped yttrium aluminum garnet laser may be utilized.³ The differential diagnosis for trichodiscoma includes basal cell carcinoma, fibrous papule, dermal nevus, and trichofolliculoma.

Basal cell carcinoma is the most common type of skin cancer.⁴ Clinically, it typically manifests as pink or flesh-colored papules on the head or neck, often with overlying ulceration or telangiectasia. Due to its association with chronic sun exposure, the median age of diagnosis for basal cell carcinoma is 68 years. Histopathologically, basal cell carcinoma is characterized by islands or nests of atypical basaloid cells with palisading cells at the periphery.⁴ Treatment depends on the location and size of the lesion, but Mohs micrographic surgery is the most common intervention on the face and ears.⁵

In contrast, fibrous papules are benign lesions that manifest clinically as small, firm, flesh-colored papules that most commonly are found on the nose.^6,7 On dermatopathology, classic findings include fibrovascular proliferation and scattered multinucleated triangular or stellate cells in the upper dermis.⁷ Due to the benign nature of the lesion, treatment is not required⁶; however, shave excision, electrodessication, and laser therapies can be attempted if the patient chooses to pursue treatment.⁸

Dermal nevus is a type of benign acquired melanocytic nevus that manifests clinically as a light-brown to flesh-colored, dome-shaped or papillomatous papule.⁹ It typically develops in areas that are exposed to the sun, including the face.¹⁰ There also have been cases of dermal nevi on the ear.¹¹ Histopathology shows melanocytic nevus cells that have completely detached from the epidermis and are located entirely in the dermis.¹² While dermal nevi are benign and treatment is not necessary, surgical excision is an option for patients who request removal.¹³

Trichofolliculoma is a benign tumor of the adnexa that shows follicular differentiation on histopathology.¹⁴ On physical examination, it manifests as an isolated flesh-colored papule or nodule with a central pore from which tufted hairs protrude. These lesions usually appear on the face or scalp and occur more commonly in women than in men. While these may be clinically indistinguishable from trichodiscomas, the absence of protruding hair in our patient’s case makes trichofolliculoma less likely. When biopsied, histopathology classically shows a cystically dilated hair follicle with keratinous material and several mature and immature branched follicular structures. Preferred treatment for trichofolliculomas is surgical excision, and recurrence is rare.¹⁴

THE DIAGNOSIS: Trichodiscoma

Histologic evaluation revealed an unremarkable epidermal surface and a subjacent well-demarcated superficial dermal nodule showing a proliferation, sometimes fascicular, of wavy and spindled fibroblasts with some stellate forms within a variably loose fibrous stroma. Some angioplasia and vascular ectasia also were seen (Figure). A diagnosis of trichodiscoma was made based on these histologic findings.

While the patient’s personal and family history of pneumothorax originally had been attributed to other causes, the diagnosis of trichodiscoma raised suspicion for Birt-Hogg-Dubé syndrome due to the classic association of skin lesions (often trichodiscomas), renal cell carcinoma, and spontaneous pneumothorax in this condition. The patient was sent for genetic testing for the associated folliculin (FLCN) gene, which was positive and thereby confirmed the diagnosis of Birt-Hogg-Dubé syndrome. At the most recent follow-up almost 2 years after initial presentation, the lesions on the earlobe were stable. The patient has since undergone screening for abdominal and renal neoplasia with negative results, and he has had no other occurrences of pneumothorax.

Our case highlights the association between trichodiscomas and Birt-Hogg-Dubé syndrome, which necessitates screening for renal cell carcinoma, pneumothorax, and lung cysts.¹ Birt-Hogg-Dubé syndrome is an autosomal- dominant disorder of the skin and lungs that is characterized by a predisposition for renal carcinoma, pneumothorax, and colon polyps as well as cutaneous markers that include fibrofolliculomas, acrochordons, and trichodiscomas; the trichodiscomas tend to manifest as numerous smooth, flesh-colored or grayish-white papules on the face, ears, neck, and/or upper trunk.¹

Trichodiscomas are benign lesions and do not require treatment²; however, if they are cosmetically bothersome to the patient, surgical excision is an option for single lesions. For more widespread cutaneous disease, combination therapy with a CO₂ laser and erbium-doped yttrium aluminum garnet laser may be utilized.³ The differential diagnosis for trichodiscoma includes basal cell carcinoma, fibrous papule, dermal nevus, and trichofolliculoma.

Basal cell carcinoma is the most common type of skin cancer.⁴ Clinically, it typically manifests as pink or flesh-colored papules on the head or neck, often with overlying ulceration or telangiectasia. Due to its association with chronic sun exposure, the median age of diagnosis for basal cell carcinoma is 68 years. Histopathologically, basal cell carcinoma is characterized by islands or nests of atypical basaloid cells with palisading cells at the periphery.⁴ Treatment depends on the location and size of the lesion, but Mohs micrographic surgery is the most common intervention on the face and ears.⁵

In contrast, fibrous papules are benign lesions that manifest clinically as small, firm, flesh-colored papules that most commonly are found on the nose.^6,7 On dermatopathology, classic findings include fibrovascular proliferation and scattered multinucleated triangular or stellate cells in the upper dermis.⁷ Due to the benign nature of the lesion, treatment is not required⁶; however, shave excision, electrodessication, and laser therapies can be attempted if the patient chooses to pursue treatment.⁸

Dermal nevus is a type of benign acquired melanocytic nevus that manifests clinically as a light-brown to flesh-colored, dome-shaped or papillomatous papule.⁹ It typically develops in areas that are exposed to the sun, including the face.¹⁰ There also have been cases of dermal nevi on the ear.¹¹ Histopathology shows melanocytic nevus cells that have completely detached from the epidermis and are located entirely in the dermis.¹² While dermal nevi are benign and treatment is not necessary, surgical excision is an option for patients who request removal.¹³

Trichofolliculoma is a benign tumor of the adnexa that shows follicular differentiation on histopathology.¹⁴ On physical examination, it manifests as an isolated flesh-colored papule or nodule with a central pore from which tufted hairs protrude. These lesions usually appear on the face or scalp and occur more commonly in women than in men. While these may be clinically indistinguishable from trichodiscomas, the absence of protruding hair in our patient’s case makes trichofolliculoma less likely. When biopsied, histopathology classically shows a cystically dilated hair follicle with keratinous material and several mature and immature branched follicular structures. Preferred treatment for trichofolliculomas is surgical excision, and recurrence is rare.¹⁴

THE DIAGNOSIS: Trichodiscoma

Histologic evaluation revealed an unremarkable epidermal surface and a subjacent well-demarcated superficial dermal nodule showing a proliferation, sometimes fascicular, of wavy and spindled fibroblasts with some stellate forms within a variably loose fibrous stroma. Some angioplasia and vascular ectasia also were seen (Figure). A diagnosis of trichodiscoma was made based on these histologic findings.

While the patient’s personal and family history of pneumothorax originally had been attributed to other causes, the diagnosis of trichodiscoma raised suspicion for Birt-Hogg-Dubé syndrome due to the classic association of skin lesions (often trichodiscomas), renal cell carcinoma, and spontaneous pneumothorax in this condition. The patient was sent for genetic testing for the associated folliculin (FLCN) gene, which was positive and thereby confirmed the diagnosis of Birt-Hogg-Dubé syndrome. At the most recent follow-up almost 2 years after initial presentation, the lesions on the earlobe were stable. The patient has since undergone screening for abdominal and renal neoplasia with negative results, and he has had no other occurrences of pneumothorax.

Our case highlights the association between trichodiscomas and Birt-Hogg-Dubé syndrome, which necessitates screening for renal cell carcinoma, pneumothorax, and lung cysts.¹ Birt-Hogg-Dubé syndrome is an autosomal- dominant disorder of the skin and lungs that is characterized by a predisposition for renal carcinoma, pneumothorax, and colon polyps as well as cutaneous markers that include fibrofolliculomas, acrochordons, and trichodiscomas; the trichodiscomas tend to manifest as numerous smooth, flesh-colored or grayish-white papules on the face, ears, neck, and/or upper trunk.¹

Trichodiscomas are benign lesions and do not require treatment²; however, if they are cosmetically bothersome to the patient, surgical excision is an option for single lesions. For more widespread cutaneous disease, combination therapy with a CO₂ laser and erbium-doped yttrium aluminum garnet laser may be utilized.³ The differential diagnosis for trichodiscoma includes basal cell carcinoma, fibrous papule, dermal nevus, and trichofolliculoma.

Basal cell carcinoma is the most common type of skin cancer.⁴ Clinically, it typically manifests as pink or flesh-colored papules on the head or neck, often with overlying ulceration or telangiectasia. Due to its association with chronic sun exposure, the median age of diagnosis for basal cell carcinoma is 68 years. Histopathologically, basal cell carcinoma is characterized by islands or nests of atypical basaloid cells with palisading cells at the periphery.⁴ Treatment depends on the location and size of the lesion, but Mohs micrographic surgery is the most common intervention on the face and ears.⁵

In contrast, fibrous papules are benign lesions that manifest clinically as small, firm, flesh-colored papules that most commonly are found on the nose.^6,7 On dermatopathology, classic findings include fibrovascular proliferation and scattered multinucleated triangular or stellate cells in the upper dermis.⁷ Due to the benign nature of the lesion, treatment is not required⁶; however, shave excision, electrodessication, and laser therapies can be attempted if the patient chooses to pursue treatment.⁸

Dermal nevus is a type of benign acquired melanocytic nevus that manifests clinically as a light-brown to flesh-colored, dome-shaped or papillomatous papule.⁹ It typically develops in areas that are exposed to the sun, including the face.¹⁰ There also have been cases of dermal nevi on the ear.¹¹ Histopathology shows melanocytic nevus cells that have completely detached from the epidermis and are located entirely in the dermis.¹² While dermal nevi are benign and treatment is not necessary, surgical excision is an option for patients who request removal.¹³

Trichofolliculoma is a benign tumor of the adnexa that shows follicular differentiation on histopathology.¹⁴ On physical examination, it manifests as an isolated flesh-colored papule or nodule with a central pore from which tufted hairs protrude. These lesions usually appear on the face or scalp and occur more commonly in women than in men. While these may be clinically indistinguishable from trichodiscomas, the absence of protruding hair in our patient’s case makes trichofolliculoma less likely. When biopsied, histopathology classically shows a cystically dilated hair follicle with keratinous material and several mature and immature branched follicular structures. Preferred treatment for trichofolliculomas is surgical excision, and recurrence is rare.¹⁴

The advent of social media has revolutionized the way patients access and consume health information. While this increased access has its merits, it also has given rise to the proliferation of medical myths, which have considerable effects on patient-physician interactions.¹ Myths are prevalent across all fields of health care, ranging from misconceptions about disease etiology and prevention to the efficacy and safety of treatments. This influx of misinformation can derail the clinical encounter, shifting the focus from evidence-based medicine to myth-busting.² The COVID-19 pandemic exacerbated this issue, as widespread lockdowns and social distancing measures limited access to in-person medical consultations, prompting patients to increasingly turn to online sources for health information that often were unreliable, thereby bypassing professional medical advice.³ Herein, we highlight the challenges and implications of common dermatology myths and provide strategies for effectively debunking these myths to enhance patient care.

Common Dermatology Myths

In dermatology, where visible and often distressing conditions such as acne and hair loss are common, the impact of myths on patient perceptions and treatment outcomes can be particularly profound. Patients often arrive for consultations with preconceived notions that are not grounded in scientific evidence. Common dermatologic myths include eczema and the efficacy of topical corticosteroids, the causes and treatment of hair loss, and risk factors associated with skin cancer.

Eczema and Topical Corticosteroids—Topical corticosteroids for eczema are safe and effective, but nonadherence due to phobias stemming from misinformation online can impede treatment.⁴ Myths such as red skin syndrome and topical corticosteroid addiction are prevalent. Red skin syndrome refers to claims that prolonged use of topical corticosteroids causes severe redness and burning of the skin and worsening eczema symptoms upon withdrawal. Topical corticosteroid addiction suggests that patients become dependent on corticosteroids, requiring higher doses over time to maintain efficacy. These misconceptions contribute to fear and avoidance of prescribed treatments.

Eczema myths often divert focus from its true etiology as a genetic inflammatory skin disease, suggesting instead that it is caused by leaky gut or food intolerances.⁴ Risks such as skin thinning and stunted growth often are exaggerated on social media and other nonmedical platforms, though these adverse effects rarely are seen when topical corticosteroids are used appropriately under medical supervision. Misinformation often is linked to companies promoting unregulated consultations, tests, or supposedly natural treatments, including herbal remedies that may surreptitiously contain corticosteroids without clear labeling. This fosters distrust of US Food and Drug Administration– approved and dermatologist-prescribed treatments, as patients may cite concerns based on experiences with or claims about unapproved products.⁴

Sunscreen and Skin Cancer—In 2018, the American Academy of Dermatology prioritized skin cancer prevention due to suboptimal public adoption of photoprotection measures.⁵ However, the proliferation of misinformation regarding sunscreen and its potential to cause skin cancer is a more pressing issue. Myths range from claims that sunscreen is ineffective to warnings that it is dangerous, with some social media influencers even suggesting that sunscreen causes skin cancer due to toxic ingredients.⁶ Oxybenzone, typically found in chemical sunscreens, has been criticized by some advocacy groups and social media influencers as a potential hormone disruptor (ie, a chemical that could interfere with hormone production).⁷ However, no conclusive evidence has shown that oxybenzone is harmful to humans. Consumer concerns often are based on animal studies in which rats are fed oxybenzone, but mathematical modeling has indicated it would take 277 years of sunscreen use by humans to match the doses used in these studies.⁸ The false association between sunscreen use and skin cancer is based on flawed studies that found higher rates of skin cancer—including melanoma—in sunscreen users compared to those who did not use sunscreen. However, those using sunscreen also were more likely to travel to sunnier climates and engage in sunbathing, and it may have been this increased sun exposure that elevated their risk for skin cancer.⁷ It is imperative that the dermatology community counteract this type of misinformation with evidence-based advice.

Hair Loss—Some patients believe that hair loss is caused by wearing hats, frequent shampooing, or even stress in a way that oversimplifies complex physiological processes. Biotin, which commonly is added to supplements for hair, skin, and nails, has been linked to potential risks, such as interference with laboratory testing and false-positive or false-negative results in critical medical tests, which can lead to misdiagnosis or inappropriate treatment.⁹ Biotin interference can result in falsely low troponin readings, which are critical in diagnosing acute myocardial infarction. Tests for other hormones such as cortisol and parathyroid hormone also are affected, potentially impacting the evaluation and management of endocrine disorders. The US Food and Drug Administration has issued warnings for patients on this topic, emphasizing the importance of informing health care providers about any biotin supplementation prior to laboratory testing. Despite its popularity, there is no substantial scientific evidence to suggest that biotin supplementation promotes hair growth in anyone other than those with deficiency, which is quite rare.⁹

Myths and the Patient-Physician Relationship

The proliferation of medical myths and misinformation affects the dynamic between patients and dermatologists in several ways. Research across various medical fields has demonstrated that misinformation can substantially impact patient behavior and treatment adherence. Like many other specialists, dermatologists often spend considerable time during consultations with patients debunking myths and correcting misconceptions, which can detract from discussing more critical aspects of the patient’s condition and treatment plan and lead to frustration and anxiety among patients. It also can be challenging for physicians to have these conversations without alienating patients, who may distrust medical recommendations and believe that natural or alternative treatments are superior. This can lead to noncompliance with prescribed treatments, and patients may instead opt to try unproven remedies they encounter online, ultimately resulting in poorer health outcomes.

Strategies to Debunk Myths

By implementing the following strategies, dermatologists can combat the spread of myths, foster trust among patients, and promote adherence to evidence-based treatments:

• Provide educational outreach. Preemptively address myths by giving patients accurate and accessible resources. Including a dedicated section on your clinic’s website with articles, frequently asked questions, videos, and links to reputable sources can be effective. Sharing patient testimonials and before-and-after photographs to demonstrate the success of evidence-based treatments also is recommended, as real-life stories can be powerful tools in dispelling myths.
• Practice effective communication. Involve patients in the decision-making process by discussing their treatment goals, preferences, and concerns. It is important to present all options clearly, including the potential benefits and adverse effects. Discuss the expected outcomes and timelines, and be transparent about the limitations of certain treatment—honesty helps build trust and sets realistic expectations.
• Conduct structured consultations. Ensure that consultations with patients follow a structured format—history, physical examination, and discussion—to help keep the focus on evidence-based practice.
• Leverage technology. Guide patients toward reliable digital patient education tools to empower them with accurate information. Hosting live sessions on social media platforms during which patients can ask questions and receive evidence-based answers also can be beneficial.

Final Thoughts

In summary, the rise of medical myths poses a considerable challenge to dermatologic practice. By understanding the sources and impacts of these myths and employing strategies to dispel them, dermatologists can better navigate the complexities of modern patient interactions and ensure that care remains grounded in scientific evidence.

The advent of social media has revolutionized the way patients access and consume health information. While this increased access has its merits, it also has given rise to the proliferation of medical myths, which have considerable effects on patient-physician interactions.¹ Myths are prevalent across all fields of health care, ranging from misconceptions about disease etiology and prevention to the efficacy and safety of treatments. This influx of misinformation can derail the clinical encounter, shifting the focus from evidence-based medicine to myth-busting.² The COVID-19 pandemic exacerbated this issue, as widespread lockdowns and social distancing measures limited access to in-person medical consultations, prompting patients to increasingly turn to online sources for health information that often were unreliable, thereby bypassing professional medical advice.³ Herein, we highlight the challenges and implications of common dermatology myths and provide strategies for effectively debunking these myths to enhance patient care.

Common Dermatology Myths

In dermatology, where visible and often distressing conditions such as acne and hair loss are common, the impact of myths on patient perceptions and treatment outcomes can be particularly profound. Patients often arrive for consultations with preconceived notions that are not grounded in scientific evidence. Common dermatologic myths include eczema and the efficacy of topical corticosteroids, the causes and treatment of hair loss, and risk factors associated with skin cancer.

Eczema and Topical Corticosteroids—Topical corticosteroids for eczema are safe and effective, but nonadherence due to phobias stemming from misinformation online can impede treatment.⁴ Myths such as red skin syndrome and topical corticosteroid addiction are prevalent. Red skin syndrome refers to claims that prolonged use of topical corticosteroids causes severe redness and burning of the skin and worsening eczema symptoms upon withdrawal. Topical corticosteroid addiction suggests that patients become dependent on corticosteroids, requiring higher doses over time to maintain efficacy. These misconceptions contribute to fear and avoidance of prescribed treatments.

Eczema myths often divert focus from its true etiology as a genetic inflammatory skin disease, suggesting instead that it is caused by leaky gut or food intolerances.⁴ Risks such as skin thinning and stunted growth often are exaggerated on social media and other nonmedical platforms, though these adverse effects rarely are seen when topical corticosteroids are used appropriately under medical supervision. Misinformation often is linked to companies promoting unregulated consultations, tests, or supposedly natural treatments, including herbal remedies that may surreptitiously contain corticosteroids without clear labeling. This fosters distrust of US Food and Drug Administration– approved and dermatologist-prescribed treatments, as patients may cite concerns based on experiences with or claims about unapproved products.⁴

Sunscreen and Skin Cancer—In 2018, the American Academy of Dermatology prioritized skin cancer prevention due to suboptimal public adoption of photoprotection measures.⁵ However, the proliferation of misinformation regarding sunscreen and its potential to cause skin cancer is a more pressing issue. Myths range from claims that sunscreen is ineffective to warnings that it is dangerous, with some social media influencers even suggesting that sunscreen causes skin cancer due to toxic ingredients.⁶ Oxybenzone, typically found in chemical sunscreens, has been criticized by some advocacy groups and social media influencers as a potential hormone disruptor (ie, a chemical that could interfere with hormone production).⁷ However, no conclusive evidence has shown that oxybenzone is harmful to humans. Consumer concerns often are based on animal studies in which rats are fed oxybenzone, but mathematical modeling has indicated it would take 277 years of sunscreen use by humans to match the doses used in these studies.⁸ The false association between sunscreen use and skin cancer is based on flawed studies that found higher rates of skin cancer—including melanoma—in sunscreen users compared to those who did not use sunscreen. However, those using sunscreen also were more likely to travel to sunnier climates and engage in sunbathing, and it may have been this increased sun exposure that elevated their risk for skin cancer.⁷ It is imperative that the dermatology community counteract this type of misinformation with evidence-based advice.

Hair Loss—Some patients believe that hair loss is caused by wearing hats, frequent shampooing, or even stress in a way that oversimplifies complex physiological processes. Biotin, which commonly is added to supplements for hair, skin, and nails, has been linked to potential risks, such as interference with laboratory testing and false-positive or false-negative results in critical medical tests, which can lead to misdiagnosis or inappropriate treatment.⁹ Biotin interference can result in falsely low troponin readings, which are critical in diagnosing acute myocardial infarction. Tests for other hormones such as cortisol and parathyroid hormone also are affected, potentially impacting the evaluation and management of endocrine disorders. The US Food and Drug Administration has issued warnings for patients on this topic, emphasizing the importance of informing health care providers about any biotin supplementation prior to laboratory testing. Despite its popularity, there is no substantial scientific evidence to suggest that biotin supplementation promotes hair growth in anyone other than those with deficiency, which is quite rare.⁹

Myths and the Patient-Physician Relationship

The proliferation of medical myths and misinformation affects the dynamic between patients and dermatologists in several ways. Research across various medical fields has demonstrated that misinformation can substantially impact patient behavior and treatment adherence. Like many other specialists, dermatologists often spend considerable time during consultations with patients debunking myths and correcting misconceptions, which can detract from discussing more critical aspects of the patient’s condition and treatment plan and lead to frustration and anxiety among patients. It also can be challenging for physicians to have these conversations without alienating patients, who may distrust medical recommendations and believe that natural or alternative treatments are superior. This can lead to noncompliance with prescribed treatments, and patients may instead opt to try unproven remedies they encounter online, ultimately resulting in poorer health outcomes.

Strategies to Debunk Myths

By implementing the following strategies, dermatologists can combat the spread of myths, foster trust among patients, and promote adherence to evidence-based treatments:

• Provide educational outreach. Preemptively address myths by giving patients accurate and accessible resources. Including a dedicated section on your clinic’s website with articles, frequently asked questions, videos, and links to reputable sources can be effective. Sharing patient testimonials and before-and-after photographs to demonstrate the success of evidence-based treatments also is recommended, as real-life stories can be powerful tools in dispelling myths.
• Practice effective communication. Involve patients in the decision-making process by discussing their treatment goals, preferences, and concerns. It is important to present all options clearly, including the potential benefits and adverse effects. Discuss the expected outcomes and timelines, and be transparent about the limitations of certain treatment—honesty helps build trust and sets realistic expectations.
• Conduct structured consultations. Ensure that consultations with patients follow a structured format—history, physical examination, and discussion—to help keep the focus on evidence-based practice.
• Leverage technology. Guide patients toward reliable digital patient education tools to empower them with accurate information. Hosting live sessions on social media platforms during which patients can ask questions and receive evidence-based answers also can be beneficial.

Final Thoughts

In summary, the rise of medical myths poses a considerable challenge to dermatologic practice. By understanding the sources and impacts of these myths and employing strategies to dispel them, dermatologists can better navigate the complexities of modern patient interactions and ensure that care remains grounded in scientific evidence.

The advent of social media has revolutionized the way patients access and consume health information. While this increased access has its merits, it also has given rise to the proliferation of medical myths, which have considerable effects on patient-physician interactions.¹ Myths are prevalent across all fields of health care, ranging from misconceptions about disease etiology and prevention to the efficacy and safety of treatments. This influx of misinformation can derail the clinical encounter, shifting the focus from evidence-based medicine to myth-busting.² The COVID-19 pandemic exacerbated this issue, as widespread lockdowns and social distancing measures limited access to in-person medical consultations, prompting patients to increasingly turn to online sources for health information that often were unreliable, thereby bypassing professional medical advice.³ Herein, we highlight the challenges and implications of common dermatology myths and provide strategies for effectively debunking these myths to enhance patient care.

Common Dermatology Myths

In dermatology, where visible and often distressing conditions such as acne and hair loss are common, the impact of myths on patient perceptions and treatment outcomes can be particularly profound. Patients often arrive for consultations with preconceived notions that are not grounded in scientific evidence. Common dermatologic myths include eczema and the efficacy of topical corticosteroids, the causes and treatment of hair loss, and risk factors associated with skin cancer.

Eczema and Topical Corticosteroids—Topical corticosteroids for eczema are safe and effective, but nonadherence due to phobias stemming from misinformation online can impede treatment.⁴ Myths such as red skin syndrome and topical corticosteroid addiction are prevalent. Red skin syndrome refers to claims that prolonged use of topical corticosteroids causes severe redness and burning of the skin and worsening eczema symptoms upon withdrawal. Topical corticosteroid addiction suggests that patients become dependent on corticosteroids, requiring higher doses over time to maintain efficacy. These misconceptions contribute to fear and avoidance of prescribed treatments.

Eczema myths often divert focus from its true etiology as a genetic inflammatory skin disease, suggesting instead that it is caused by leaky gut or food intolerances.⁴ Risks such as skin thinning and stunted growth often are exaggerated on social media and other nonmedical platforms, though these adverse effects rarely are seen when topical corticosteroids are used appropriately under medical supervision. Misinformation often is linked to companies promoting unregulated consultations, tests, or supposedly natural treatments, including herbal remedies that may surreptitiously contain corticosteroids without clear labeling. This fosters distrust of US Food and Drug Administration– approved and dermatologist-prescribed treatments, as patients may cite concerns based on experiences with or claims about unapproved products.⁴

Sunscreen and Skin Cancer—In 2018, the American Academy of Dermatology prioritized skin cancer prevention due to suboptimal public adoption of photoprotection measures.⁵ However, the proliferation of misinformation regarding sunscreen and its potential to cause skin cancer is a more pressing issue. Myths range from claims that sunscreen is ineffective to warnings that it is dangerous, with some social media influencers even suggesting that sunscreen causes skin cancer due to toxic ingredients.⁶ Oxybenzone, typically found in chemical sunscreens, has been criticized by some advocacy groups and social media influencers as a potential hormone disruptor (ie, a chemical that could interfere with hormone production).⁷ However, no conclusive evidence has shown that oxybenzone is harmful to humans. Consumer concerns often are based on animal studies in which rats are fed oxybenzone, but mathematical modeling has indicated it would take 277 years of sunscreen use by humans to match the doses used in these studies.⁸ The false association between sunscreen use and skin cancer is based on flawed studies that found higher rates of skin cancer—including melanoma—in sunscreen users compared to those who did not use sunscreen. However, those using sunscreen also were more likely to travel to sunnier climates and engage in sunbathing, and it may have been this increased sun exposure that elevated their risk for skin cancer.⁷ It is imperative that the dermatology community counteract this type of misinformation with evidence-based advice.

Hair Loss—Some patients believe that hair loss is caused by wearing hats, frequent shampooing, or even stress in a way that oversimplifies complex physiological processes. Biotin, which commonly is added to supplements for hair, skin, and nails, has been linked to potential risks, such as interference with laboratory testing and false-positive or false-negative results in critical medical tests, which can lead to misdiagnosis or inappropriate treatment.⁹ Biotin interference can result in falsely low troponin readings, which are critical in diagnosing acute myocardial infarction. Tests for other hormones such as cortisol and parathyroid hormone also are affected, potentially impacting the evaluation and management of endocrine disorders. The US Food and Drug Administration has issued warnings for patients on this topic, emphasizing the importance of informing health care providers about any biotin supplementation prior to laboratory testing. Despite its popularity, there is no substantial scientific evidence to suggest that biotin supplementation promotes hair growth in anyone other than those with deficiency, which is quite rare.⁹

Myths and the Patient-Physician Relationship

The proliferation of medical myths and misinformation affects the dynamic between patients and dermatologists in several ways. Research across various medical fields has demonstrated that misinformation can substantially impact patient behavior and treatment adherence. Like many other specialists, dermatologists often spend considerable time during consultations with patients debunking myths and correcting misconceptions, which can detract from discussing more critical aspects of the patient’s condition and treatment plan and lead to frustration and anxiety among patients. It also can be challenging for physicians to have these conversations without alienating patients, who may distrust medical recommendations and believe that natural or alternative treatments are superior. This can lead to noncompliance with prescribed treatments, and patients may instead opt to try unproven remedies they encounter online, ultimately resulting in poorer health outcomes.

Strategies to Debunk Myths

By implementing the following strategies, dermatologists can combat the spread of myths, foster trust among patients, and promote adherence to evidence-based treatments:

• Provide educational outreach. Preemptively address myths by giving patients accurate and accessible resources. Including a dedicated section on your clinic’s website with articles, frequently asked questions, videos, and links to reputable sources can be effective. Sharing patient testimonials and before-and-after photographs to demonstrate the success of evidence-based treatments also is recommended, as real-life stories can be powerful tools in dispelling myths.
• Practice effective communication. Involve patients in the decision-making process by discussing their treatment goals, preferences, and concerns. It is important to present all options clearly, including the potential benefits and adverse effects. Discuss the expected outcomes and timelines, and be transparent about the limitations of certain treatment—honesty helps build trust and sets realistic expectations.
• Conduct structured consultations. Ensure that consultations with patients follow a structured format—history, physical examination, and discussion—to help keep the focus on evidence-based practice.
• Leverage technology. Guide patients toward reliable digital patient education tools to empower them with accurate information. Hosting live sessions on social media platforms during which patients can ask questions and receive evidence-based answers also can be beneficial.

Final Thoughts

In summary, the rise of medical myths poses a considerable challenge to dermatologic practice. By understanding the sources and impacts of these myths and employing strategies to dispel them, dermatologists can better navigate the complexities of modern patient interactions and ensure that care remains grounded in scientific evidence.

The year was 2023, and I was on my way to the American Academy of Dermatology meeting in New Orleans, Louisiana. “Geaux Tigers!” I exclaimed to a stranger as she walked by in her purple and gold shoes and scrubs. We chatted for a minute or two about Louisiana State University (LSU) football, then went our separate ways. Later that day, in the hands-on wound closures workshop, I was surprised to see my new acquaintance step up to the podium to lecture, then make rounds across the room to instruct residents. I didn’t know it at the time, but those purple and gold shoes sparked a conversation with a fellowship program director who would become one of my most valued mentors.

I didn’t set out to find a mentor that day—I simply was excited to connect with a fellow Tigers fan. But mentorship often finds us unexpectedly, and that encounter serves as a reminder that mentorship doesn’t always start in a formal setting. Sometimes it begins with a quick conversation in the right place at the right time. This story is one of many experiences that taught me valuable lessons about mentorship—its importance, how it can grow naturally, and the impact it can have.

Residency is a pivotal time in a physician’s life, filled with rapid learning, complex challenges, and new professional relationships. Amidst the long hours and heavy responsibilities, mentorship stands out as a support system for guiding residents toward professional and personal growth. Herein, I share more about my experiences with mentorship in residency, the lessons I have learned, and how they can serve as guidance for residents.

The Value of Mentorship

Mentorship in residency has been shown to have a major impact on career satisfaction, clinical confidence, and professional development.¹ A good mentor offers more than just advice—he or she can provide a model of professionalism and skills that resonates with the mentee’s own aspirations. Mentorship can help residents refine their clinical skills, navigate the complexities of patient care, engage in research, and connect with professionals in their field.²

Mentorship can be sought intentionally or arise naturally from shared interests and connections. Some residents reach out to potential mentors directly through emails, set up one-on-one meetings, or shadow them to gain firsthand experience. Others find mentorship simply by putting themselves in situations that foster these connections, such as attending conferences or lectures. Both approaches can lead to impactful relationships that shape a resident’s career and personal growth.

For residents involved in research, an effective faculty research mentor is particularly impactful. Studies show that residents who work with knowledgeable research mentors are more likely to experience success and productivity in their research efforts.³ Research mentors can provide essential guidance—from helping formulate research questions to navigating the complexities of publishing—which makes them invaluable in a resident’s academic development.

If you have interests in specific areas not heavily emphasized within your residency program (eg, transplantation dermatology, hair restoration, cutaneous lymphoma), consider checking within your broader medical community for specialists. Many dermatologists and other specialists welcome the opportunity to mentor residents who express a sincere interest in learning. By reaching out to these professionals, you not only expand your clinical knowledge but also gain access to niche areas of dermatology that can shape and refine your future practice. Often, these experiences lead to invaluable mentorships that may otherwise be unavailable within your immediate training environment.

Networking Through Professional Society Rotational and Mentorship Programs

The Women’s Dermatologic Society (https://www.womensderm.org/), the American Society for Dermatologic Surgery (https://www.asds.net/), and the American Society for Laser Medicine and Surgery (https://www.aslms.org/) all provide excellent formalized mentorship or preceptorship programs. Check their websites for application requirements and timelines. Participating in these programs is a great way to network with experts in dermatology, providing a structured way to interact with physicians who share your interests. Whether you are interested in medical dermatology, surgery, pediatrics, dermatopathology, or cosmetics, there are many mentors who greatly enjoy sharing their knowledge and experience with residents. Oftentimes, these programs include stipends to assist with costs that are awarded as accolades that can enhance your curriculum vitae. Engaging in these recognized preceptorship programs often builds lasting connections and ensures that both mentor and mentee have a vested interest in the relationship’s success.

Making Connections at Conferences and Maximizing Hands-on Learning

Professional conferences offer valuable opportunities to connect with mentors, whether you are proactively seeking mentorship or simply allowing connections to happen naturally. Conferences such as those of the American Academy of Dermatology and American Society for Dermatologic Surgery publish educational booklets and schedules online prior to the event, giving you a chance to explore both topics and speaker names ahead of time. This can be an excellent opportunity to create a day-by-day game plan, identifying sessions and lectures of interest as well as specific authors or experts you might like to meet. Planning in advance makes it easier to engage with leaders in the field, introduce yourself, and make meaningful connections.

Oftentimes, these society meetings offer hands-on courses, which are a great way to meet mentors and learn from direct instruction. Instructors for these courses often are leaders in dermatology who are passionate about teaching. With small group sizes, hands-on courses offer both technical skill-building opportunities and a chance to connect personally with instructors. Take a moment to introduce yourself and engage in a quick conversation, and if you feel it is appropriate, follow up with an email after the conference. This helps keep the connection alive beyond the event and may open doors for future mentorship opportunities.

Away Rotations

For residents looking to build specialized skills and connect with mentors outside their own program—especially those considering fellowship—away rotations can be a great tool. Though it may require using vacation time, an away rotation offers immersive learning in a particular area while providing opportunities to observe new mentors and establish relationships within a desired subspecialty or program. By simply reaching out and expressing interest, residents can connect with physicians who may become lasting mentors and advocates.

Building a Mentor-Mentee Relationship

A meaningful mentor-mentee relationship requires time, effort, and effective communication, with clear expectations around mentorship goals, time commitments, and how both parties envision the relationship evolving.⁴ Ideally, mentees should feel comfortable sharing their goals with mentors and asking for feedback. In the right context, a simple and effective practice is to send your mentor a brief update on your progress every few months. This could be a quick email sharing your latest projects, ideas, and/or achievements. By regularly checking in, you show your mentor that you are committed to growing from their guidance and respect their time.

The Lasting Impact of Mentorship

The effects of mentorship in residency extend well beyond the training years, as mentors often become lifelong guides and professional advocates for their mentees.⁵ Residency often is the last time a resident trains under the direct supervision of an attending physician, making it a unique and formative period. After graduation, many new physicians find the transition to independent practice challenging, and the “real world” can be a shock. Having a mentor during this time, or maintaining connections with mentors from residency, can be invaluable. Mentors can offer advice, act as sounding boards, and remind new graduates of the importance of being lifelong learners. These relationships help ease the transition into practice, instilling a commitment to continuous improvement and professional growth. For me, a conversation about LSU football at the AAD meeting in New Orleans exemplifies how mentorship can begin in the most unexpected ways. That casual exchange led to an away rotation, a fellowship interview, connections at national meetings, and the start of what I hope will be a lifelong friendship.

The year was 2023, and I was on my way to the American Academy of Dermatology meeting in New Orleans, Louisiana. “Geaux Tigers!” I exclaimed to a stranger as she walked by in her purple and gold shoes and scrubs. We chatted for a minute or two about Louisiana State University (LSU) football, then went our separate ways. Later that day, in the hands-on wound closures workshop, I was surprised to see my new acquaintance step up to the podium to lecture, then make rounds across the room to instruct residents. I didn’t know it at the time, but those purple and gold shoes sparked a conversation with a fellowship program director who would become one of my most valued mentors.

I didn’t set out to find a mentor that day—I simply was excited to connect with a fellow Tigers fan. But mentorship often finds us unexpectedly, and that encounter serves as a reminder that mentorship doesn’t always start in a formal setting. Sometimes it begins with a quick conversation in the right place at the right time. This story is one of many experiences that taught me valuable lessons about mentorship—its importance, how it can grow naturally, and the impact it can have.

Residency is a pivotal time in a physician’s life, filled with rapid learning, complex challenges, and new professional relationships. Amidst the long hours and heavy responsibilities, mentorship stands out as a support system for guiding residents toward professional and personal growth. Herein, I share more about my experiences with mentorship in residency, the lessons I have learned, and how they can serve as guidance for residents.

The Value of Mentorship

Mentorship in residency has been shown to have a major impact on career satisfaction, clinical confidence, and professional development.¹ A good mentor offers more than just advice—he or she can provide a model of professionalism and skills that resonates with the mentee’s own aspirations. Mentorship can help residents refine their clinical skills, navigate the complexities of patient care, engage in research, and connect with professionals in their field.²

Mentorship can be sought intentionally or arise naturally from shared interests and connections. Some residents reach out to potential mentors directly through emails, set up one-on-one meetings, or shadow them to gain firsthand experience. Others find mentorship simply by putting themselves in situations that foster these connections, such as attending conferences or lectures. Both approaches can lead to impactful relationships that shape a resident’s career and personal growth.

For residents involved in research, an effective faculty research mentor is particularly impactful. Studies show that residents who work with knowledgeable research mentors are more likely to experience success and productivity in their research efforts.³ Research mentors can provide essential guidance—from helping formulate research questions to navigating the complexities of publishing—which makes them invaluable in a resident’s academic development.

If you have interests in specific areas not heavily emphasized within your residency program (eg, transplantation dermatology, hair restoration, cutaneous lymphoma), consider checking within your broader medical community for specialists. Many dermatologists and other specialists welcome the opportunity to mentor residents who express a sincere interest in learning. By reaching out to these professionals, you not only expand your clinical knowledge but also gain access to niche areas of dermatology that can shape and refine your future practice. Often, these experiences lead to invaluable mentorships that may otherwise be unavailable within your immediate training environment.

Networking Through Professional Society Rotational and Mentorship Programs

The Women’s Dermatologic Society (https://www.womensderm.org/), the American Society for Dermatologic Surgery (https://www.asds.net/), and the American Society for Laser Medicine and Surgery (https://www.aslms.org/) all provide excellent formalized mentorship or preceptorship programs. Check their websites for application requirements and timelines. Participating in these programs is a great way to network with experts in dermatology, providing a structured way to interact with physicians who share your interests. Whether you are interested in medical dermatology, surgery, pediatrics, dermatopathology, or cosmetics, there are many mentors who greatly enjoy sharing their knowledge and experience with residents. Oftentimes, these programs include stipends to assist with costs that are awarded as accolades that can enhance your curriculum vitae. Engaging in these recognized preceptorship programs often builds lasting connections and ensures that both mentor and mentee have a vested interest in the relationship’s success.

Making Connections at Conferences and Maximizing Hands-on Learning

Professional conferences offer valuable opportunities to connect with mentors, whether you are proactively seeking mentorship or simply allowing connections to happen naturally. Conferences such as those of the American Academy of Dermatology and American Society for Dermatologic Surgery publish educational booklets and schedules online prior to the event, giving you a chance to explore both topics and speaker names ahead of time. This can be an excellent opportunity to create a day-by-day game plan, identifying sessions and lectures of interest as well as specific authors or experts you might like to meet. Planning in advance makes it easier to engage with leaders in the field, introduce yourself, and make meaningful connections.

Oftentimes, these society meetings offer hands-on courses, which are a great way to meet mentors and learn from direct instruction. Instructors for these courses often are leaders in dermatology who are passionate about teaching. With small group sizes, hands-on courses offer both technical skill-building opportunities and a chance to connect personally with instructors. Take a moment to introduce yourself and engage in a quick conversation, and if you feel it is appropriate, follow up with an email after the conference. This helps keep the connection alive beyond the event and may open doors for future mentorship opportunities.

Away Rotations

For residents looking to build specialized skills and connect with mentors outside their own program—especially those considering fellowship—away rotations can be a great tool. Though it may require using vacation time, an away rotation offers immersive learning in a particular area while providing opportunities to observe new mentors and establish relationships within a desired subspecialty or program. By simply reaching out and expressing interest, residents can connect with physicians who may become lasting mentors and advocates.

Building a Mentor-Mentee Relationship

A meaningful mentor-mentee relationship requires time, effort, and effective communication, with clear expectations around mentorship goals, time commitments, and how both parties envision the relationship evolving.⁴ Ideally, mentees should feel comfortable sharing their goals with mentors and asking for feedback. In the right context, a simple and effective practice is to send your mentor a brief update on your progress every few months. This could be a quick email sharing your latest projects, ideas, and/or achievements. By regularly checking in, you show your mentor that you are committed to growing from their guidance and respect their time.

The Lasting Impact of Mentorship

The effects of mentorship in residency extend well beyond the training years, as mentors often become lifelong guides and professional advocates for their mentees.⁵ Residency often is the last time a resident trains under the direct supervision of an attending physician, making it a unique and formative period. After graduation, many new physicians find the transition to independent practice challenging, and the “real world” can be a shock. Having a mentor during this time, or maintaining connections with mentors from residency, can be invaluable. Mentors can offer advice, act as sounding boards, and remind new graduates of the importance of being lifelong learners. These relationships help ease the transition into practice, instilling a commitment to continuous improvement and professional growth. For me, a conversation about LSU football at the AAD meeting in New Orleans exemplifies how mentorship can begin in the most unexpected ways. That casual exchange led to an away rotation, a fellowship interview, connections at national meetings, and the start of what I hope will be a lifelong friendship.

The year was 2023, and I was on my way to the American Academy of Dermatology meeting in New Orleans, Louisiana. “Geaux Tigers!” I exclaimed to a stranger as she walked by in her purple and gold shoes and scrubs. We chatted for a minute or two about Louisiana State University (LSU) football, then went our separate ways. Later that day, in the hands-on wound closures workshop, I was surprised to see my new acquaintance step up to the podium to lecture, then make rounds across the room to instruct residents. I didn’t know it at the time, but those purple and gold shoes sparked a conversation with a fellowship program director who would become one of my most valued mentors.

I didn’t set out to find a mentor that day—I simply was excited to connect with a fellow Tigers fan. But mentorship often finds us unexpectedly, and that encounter serves as a reminder that mentorship doesn’t always start in a formal setting. Sometimes it begins with a quick conversation in the right place at the right time. This story is one of many experiences that taught me valuable lessons about mentorship—its importance, how it can grow naturally, and the impact it can have.

Residency is a pivotal time in a physician’s life, filled with rapid learning, complex challenges, and new professional relationships. Amidst the long hours and heavy responsibilities, mentorship stands out as a support system for guiding residents toward professional and personal growth. Herein, I share more about my experiences with mentorship in residency, the lessons I have learned, and how they can serve as guidance for residents.

The Value of Mentorship

Mentorship in residency has been shown to have a major impact on career satisfaction, clinical confidence, and professional development.¹ A good mentor offers more than just advice—he or she can provide a model of professionalism and skills that resonates with the mentee’s own aspirations. Mentorship can help residents refine their clinical skills, navigate the complexities of patient care, engage in research, and connect with professionals in their field.²

Mentorship can be sought intentionally or arise naturally from shared interests and connections. Some residents reach out to potential mentors directly through emails, set up one-on-one meetings, or shadow them to gain firsthand experience. Others find mentorship simply by putting themselves in situations that foster these connections, such as attending conferences or lectures. Both approaches can lead to impactful relationships that shape a resident’s career and personal growth.

For residents involved in research, an effective faculty research mentor is particularly impactful. Studies show that residents who work with knowledgeable research mentors are more likely to experience success and productivity in their research efforts.³ Research mentors can provide essential guidance—from helping formulate research questions to navigating the complexities of publishing—which makes them invaluable in a resident’s academic development.

If you have interests in specific areas not heavily emphasized within your residency program (eg, transplantation dermatology, hair restoration, cutaneous lymphoma), consider checking within your broader medical community for specialists. Many dermatologists and other specialists welcome the opportunity to mentor residents who express a sincere interest in learning. By reaching out to these professionals, you not only expand your clinical knowledge but also gain access to niche areas of dermatology that can shape and refine your future practice. Often, these experiences lead to invaluable mentorships that may otherwise be unavailable within your immediate training environment.

Networking Through Professional Society Rotational and Mentorship Programs

The Women’s Dermatologic Society (https://www.womensderm.org/), the American Society for Dermatologic Surgery (https://www.asds.net/), and the American Society for Laser Medicine and Surgery (https://www.aslms.org/) all provide excellent formalized mentorship or preceptorship programs. Check their websites for application requirements and timelines. Participating in these programs is a great way to network with experts in dermatology, providing a structured way to interact with physicians who share your interests. Whether you are interested in medical dermatology, surgery, pediatrics, dermatopathology, or cosmetics, there are many mentors who greatly enjoy sharing their knowledge and experience with residents. Oftentimes, these programs include stipends to assist with costs that are awarded as accolades that can enhance your curriculum vitae. Engaging in these recognized preceptorship programs often builds lasting connections and ensures that both mentor and mentee have a vested interest in the relationship’s success.

Making Connections at Conferences and Maximizing Hands-on Learning

Professional conferences offer valuable opportunities to connect with mentors, whether you are proactively seeking mentorship or simply allowing connections to happen naturally. Conferences such as those of the American Academy of Dermatology and American Society for Dermatologic Surgery publish educational booklets and schedules online prior to the event, giving you a chance to explore both topics and speaker names ahead of time. This can be an excellent opportunity to create a day-by-day game plan, identifying sessions and lectures of interest as well as specific authors or experts you might like to meet. Planning in advance makes it easier to engage with leaders in the field, introduce yourself, and make meaningful connections.

Oftentimes, these society meetings offer hands-on courses, which are a great way to meet mentors and learn from direct instruction. Instructors for these courses often are leaders in dermatology who are passionate about teaching. With small group sizes, hands-on courses offer both technical skill-building opportunities and a chance to connect personally with instructors. Take a moment to introduce yourself and engage in a quick conversation, and if you feel it is appropriate, follow up with an email after the conference. This helps keep the connection alive beyond the event and may open doors for future mentorship opportunities.

Away Rotations

For residents looking to build specialized skills and connect with mentors outside their own program—especially those considering fellowship—away rotations can be a great tool. Though it may require using vacation time, an away rotation offers immersive learning in a particular area while providing opportunities to observe new mentors and establish relationships within a desired subspecialty or program. By simply reaching out and expressing interest, residents can connect with physicians who may become lasting mentors and advocates.

Building a Mentor-Mentee Relationship

A meaningful mentor-mentee relationship requires time, effort, and effective communication, with clear expectations around mentorship goals, time commitments, and how both parties envision the relationship evolving.⁴ Ideally, mentees should feel comfortable sharing their goals with mentors and asking for feedback. In the right context, a simple and effective practice is to send your mentor a brief update on your progress every few months. This could be a quick email sharing your latest projects, ideas, and/or achievements. By regularly checking in, you show your mentor that you are committed to growing from their guidance and respect their time.

The Lasting Impact of Mentorship

The effects of mentorship in residency extend well beyond the training years, as mentors often become lifelong guides and professional advocates for their mentees.⁵ Residency often is the last time a resident trains under the direct supervision of an attending physician, making it a unique and formative period. After graduation, many new physicians find the transition to independent practice challenging, and the “real world” can be a shock. Having a mentor during this time, or maintaining connections with mentors from residency, can be invaluable. Mentors can offer advice, act as sounding boards, and remind new graduates of the importance of being lifelong learners. These relationships help ease the transition into practice, instilling a commitment to continuous improvement and professional growth. For me, a conversation about LSU football at the AAD meeting in New Orleans exemplifies how mentorship can begin in the most unexpected ways. That casual exchange led to an away rotation, a fellowship interview, connections at national meetings, and the start of what I hope will be a lifelong friendship.

THE DIAGNOSIS: Hidradenocarcinoma

Both the original and recurrent lesions were interpreted as a chondroid syringoma, a benign adnexal tumor; however, the third biopsy of the lesion revealed a low-grade adnexal neoplasm with irregular nests of variably sized epithelial cells demonstrating mild nuclear atypia and low mitotic activity. Given the multiple recurrences, accelerated growth, and more aggressive histologic findings, the patient was referred to our clinic for surgical management.

We elected to perform modified Mohs micrographic surgery (MMS) with permanent tissue sections to enable the application of immunohistochemical stains to fully characterize the tumor. Histopathology showed a poorly circumscribed infiltrative dermal neoplasm composed of basaloid cells with a solid and cystic growth pattern in a background of hyalinized, fibrotic stroma (Figure, A and B). There were focal clear cell and squamous features as well as focal ductal differentiation (Figure, C and D). No obvious papillary structures were noted. The tumor cells were positive for D2-40, and staining for CD31 failed to reveal lymphovascular invasion. Based on the infiltrative features in conjunction with the findings from the prior biopsies, a diagnosis of hidradenocarcinoma (HAC) was made. Deep and peripheral margins were cleared after 2 stages of MMS.

Initially described in 1954, HAC is an exceedingly rare adnexal tumor of apocrine and eccrine derivation.¹ Historically, nomenclature for this entity has varied in the literature, including synonyms such as malignant nodular hidradenoma, malignant acrospiroma, solid-cystic adenocarcinoma, and malignant clear cell myoepithelioma.^2,3 Approximately 6% of all malignant eccrine tumors worldwide are HACs, which account for only 1 in 13,000 dermatopathology specimens.¹ These tumors may transform from clear cell hidradenomas (their benign counterparts) but more commonly arise de novo. Compared to benign hidradenomas, HACs are poorly circumscribed with infiltrative growth patterns on histopathology and may exhibit nuclear pleomorphism, prominent mitotic activity, necrosis, and perineural or vascular invasion.²

Clinically, HAC manifests as a 1- to 5-cm, solitary, firm, intradermal pink or violaceous nodule with possible ulceration.^2,4 The nodule often is asymptomatic but may be tender, as in our patient. There seems to be no clear anatomic site of predilection, with approximately 42% of HACs localized to the head and neck and the remainder occurring on the trunk, arms, and legs.^3,5-7 Females and males are affected equally, and lesions tend to arise in the seventh decade of life.⁷

Reports in the literature suggest that HAC is a very aggressive tumor with a generally poor prognosis.¹ Several studies have found that up to half of tumors locally recur despite aggressive surgical management, and metastasis occurs in 20% to 60% of patients.^3,8 However, a large study of US Surveillance, Epidemiology, and End Results data investigating the clinicopathologic characteristics of 289 patients with HAC revealed a more favorable prognosis.⁷ Mean overall survival and cancer-specific survival were greater than 13 years, and 10-year overall survival and cancer-specific survival rates were 60.2% and 90.5%, respectively.

Traditionally used to treat keratinocyte carcinomas, including basal cell carcinoma and squamous cell carcinoma, complete margin assessment with MMS is increasingly being utilized in the management of other cutaneous malignancies, including adnexal tumors.⁸ Due to its rarity, there remains no standard optimal treatment approach for HAC. One small retrospective study of 10 patients with HAC treated with MMS demonstrated favorable outcomes with no cases of recurrence, metastasis, or diseaserelated mortality in a mean 7-year follow-up period.⁹

Whole-body positron emission tomography/computed tomography performed in our patient approximately 1 month after MMS revealed mildly hypermetabolic left inguinal lymph nodes, which were thought to be reactive, and a question of small hypermetabolic foci in the liver. Follow-up computed tomography of the abdomen subsequently was performed and was negative for hepatic metastases. The patient will be monitored closely for local recurrence; however, the clearance of the tumor with MMS, which allowed complete margin assessment, is encouraging and supports MMS as superior to traditional surgical excision in the treatment of HAC. At his most recent examination 17 months after Mohs surgery, the patient remained tumor free.

Aggressive digital papillary adenocarcinoma (ADPA) is a rare malignant tumor originating in the sweat glands that can occur on the first toe but most commonly arises on the fingers. While both HAC and ADPA can manifest with an infiltrative growth pattern and cytologic atypia, ADPA classically reveals a well-circumscribed multinodular tumor in the dermis comprised of solid and cystic proliferation as well as papillary projections. In addition, ADPA has been described as having back-to-back glandular and ductal structures.¹⁰ Giant cell tumor of the tendon sheath is a benign fibrohistiocytic tumor that also typically manifests on the fingers but rarely can occur on the foot, including the first toe.^11,12 This tumor is more common in women and most frequently affects individuals aged 30 to 50 years.¹² Microscopically, giant cell tumor of the tendon sheath is characterized by a proliferation of osteoclastlike giant cells, epithelioid histiocytelike cells, mononuclear cells, and xanthomatous cells among collagenous bands.¹¹

Osteosarcoma is an uncommon tumor of osteoidproducing cells that usually arises in the metaphysis of long bones and manifests as a tender subcutaneous mass. It has a bimodal age distribution, peaking in adolescents and adults older than 65 years.¹³ While very rare, osteosarcoma has been reported to occur in the bones of the feet, including the phalanges.¹⁴ Given the recurrent nature of our patient’s tumor, metastasis should always be considered; however, in his case, full-body imaging was negative for additional malignancy.

THE DIAGNOSIS: Hidradenocarcinoma

Both the original and recurrent lesions were interpreted as a chondroid syringoma, a benign adnexal tumor; however, the third biopsy of the lesion revealed a low-grade adnexal neoplasm with irregular nests of variably sized epithelial cells demonstrating mild nuclear atypia and low mitotic activity. Given the multiple recurrences, accelerated growth, and more aggressive histologic findings, the patient was referred to our clinic for surgical management.

We elected to perform modified Mohs micrographic surgery (MMS) with permanent tissue sections to enable the application of immunohistochemical stains to fully characterize the tumor. Histopathology showed a poorly circumscribed infiltrative dermal neoplasm composed of basaloid cells with a solid and cystic growth pattern in a background of hyalinized, fibrotic stroma (Figure, A and B). There were focal clear cell and squamous features as well as focal ductal differentiation (Figure, C and D). No obvious papillary structures were noted. The tumor cells were positive for D2-40, and staining for CD31 failed to reveal lymphovascular invasion. Based on the infiltrative features in conjunction with the findings from the prior biopsies, a diagnosis of hidradenocarcinoma (HAC) was made. Deep and peripheral margins were cleared after 2 stages of MMS.

Initially described in 1954, HAC is an exceedingly rare adnexal tumor of apocrine and eccrine derivation.¹ Historically, nomenclature for this entity has varied in the literature, including synonyms such as malignant nodular hidradenoma, malignant acrospiroma, solid-cystic adenocarcinoma, and malignant clear cell myoepithelioma.^2,3 Approximately 6% of all malignant eccrine tumors worldwide are HACs, which account for only 1 in 13,000 dermatopathology specimens.¹ These tumors may transform from clear cell hidradenomas (their benign counterparts) but more commonly arise de novo. Compared to benign hidradenomas, HACs are poorly circumscribed with infiltrative growth patterns on histopathology and may exhibit nuclear pleomorphism, prominent mitotic activity, necrosis, and perineural or vascular invasion.²

Clinically, HAC manifests as a 1- to 5-cm, solitary, firm, intradermal pink or violaceous nodule with possible ulceration.^2,4 The nodule often is asymptomatic but may be tender, as in our patient. There seems to be no clear anatomic site of predilection, with approximately 42% of HACs localized to the head and neck and the remainder occurring on the trunk, arms, and legs.^3,5-7 Females and males are affected equally, and lesions tend to arise in the seventh decade of life.⁷

Reports in the literature suggest that HAC is a very aggressive tumor with a generally poor prognosis.¹ Several studies have found that up to half of tumors locally recur despite aggressive surgical management, and metastasis occurs in 20% to 60% of patients.^3,8 However, a large study of US Surveillance, Epidemiology, and End Results data investigating the clinicopathologic characteristics of 289 patients with HAC revealed a more favorable prognosis.⁷ Mean overall survival and cancer-specific survival were greater than 13 years, and 10-year overall survival and cancer-specific survival rates were 60.2% and 90.5%, respectively.

Traditionally used to treat keratinocyte carcinomas, including basal cell carcinoma and squamous cell carcinoma, complete margin assessment with MMS is increasingly being utilized in the management of other cutaneous malignancies, including adnexal tumors.⁸ Due to its rarity, there remains no standard optimal treatment approach for HAC. One small retrospective study of 10 patients with HAC treated with MMS demonstrated favorable outcomes with no cases of recurrence, metastasis, or diseaserelated mortality in a mean 7-year follow-up period.⁹

Whole-body positron emission tomography/computed tomography performed in our patient approximately 1 month after MMS revealed mildly hypermetabolic left inguinal lymph nodes, which were thought to be reactive, and a question of small hypermetabolic foci in the liver. Follow-up computed tomography of the abdomen subsequently was performed and was negative for hepatic metastases. The patient will be monitored closely for local recurrence; however, the clearance of the tumor with MMS, which allowed complete margin assessment, is encouraging and supports MMS as superior to traditional surgical excision in the treatment of HAC. At his most recent examination 17 months after Mohs surgery, the patient remained tumor free.

Aggressive digital papillary adenocarcinoma (ADPA) is a rare malignant tumor originating in the sweat glands that can occur on the first toe but most commonly arises on the fingers. While both HAC and ADPA can manifest with an infiltrative growth pattern and cytologic atypia, ADPA classically reveals a well-circumscribed multinodular tumor in the dermis comprised of solid and cystic proliferation as well as papillary projections. In addition, ADPA has been described as having back-to-back glandular and ductal structures.¹⁰ Giant cell tumor of the tendon sheath is a benign fibrohistiocytic tumor that also typically manifests on the fingers but rarely can occur on the foot, including the first toe.^11,12 This tumor is more common in women and most frequently affects individuals aged 30 to 50 years.¹² Microscopically, giant cell tumor of the tendon sheath is characterized by a proliferation of osteoclastlike giant cells, epithelioid histiocytelike cells, mononuclear cells, and xanthomatous cells among collagenous bands.¹¹

Osteosarcoma is an uncommon tumor of osteoidproducing cells that usually arises in the metaphysis of long bones and manifests as a tender subcutaneous mass. It has a bimodal age distribution, peaking in adolescents and adults older than 65 years.¹³ While very rare, osteosarcoma has been reported to occur in the bones of the feet, including the phalanges.¹⁴ Given the recurrent nature of our patient’s tumor, metastasis should always be considered; however, in his case, full-body imaging was negative for additional malignancy.

THE DIAGNOSIS: Hidradenocarcinoma

Both the original and recurrent lesions were interpreted as a chondroid syringoma, a benign adnexal tumor; however, the third biopsy of the lesion revealed a low-grade adnexal neoplasm with irregular nests of variably sized epithelial cells demonstrating mild nuclear atypia and low mitotic activity. Given the multiple recurrences, accelerated growth, and more aggressive histologic findings, the patient was referred to our clinic for surgical management.

We elected to perform modified Mohs micrographic surgery (MMS) with permanent tissue sections to enable the application of immunohistochemical stains to fully characterize the tumor. Histopathology showed a poorly circumscribed infiltrative dermal neoplasm composed of basaloid cells with a solid and cystic growth pattern in a background of hyalinized, fibrotic stroma (Figure, A and B). There were focal clear cell and squamous features as well as focal ductal differentiation (Figure, C and D). No obvious papillary structures were noted. The tumor cells were positive for D2-40, and staining for CD31 failed to reveal lymphovascular invasion. Based on the infiltrative features in conjunction with the findings from the prior biopsies, a diagnosis of hidradenocarcinoma (HAC) was made. Deep and peripheral margins were cleared after 2 stages of MMS.

Initially described in 1954, HAC is an exceedingly rare adnexal tumor of apocrine and eccrine derivation.¹ Historically, nomenclature for this entity has varied in the literature, including synonyms such as malignant nodular hidradenoma, malignant acrospiroma, solid-cystic adenocarcinoma, and malignant clear cell myoepithelioma.^2,3 Approximately 6% of all malignant eccrine tumors worldwide are HACs, which account for only 1 in 13,000 dermatopathology specimens.¹ These tumors may transform from clear cell hidradenomas (their benign counterparts) but more commonly arise de novo. Compared to benign hidradenomas, HACs are poorly circumscribed with infiltrative growth patterns on histopathology and may exhibit nuclear pleomorphism, prominent mitotic activity, necrosis, and perineural or vascular invasion.²

Clinically, HAC manifests as a 1- to 5-cm, solitary, firm, intradermal pink or violaceous nodule with possible ulceration.^2,4 The nodule often is asymptomatic but may be tender, as in our patient. There seems to be no clear anatomic site of predilection, with approximately 42% of HACs localized to the head and neck and the remainder occurring on the trunk, arms, and legs.^3,5-7 Females and males are affected equally, and lesions tend to arise in the seventh decade of life.⁷

Reports in the literature suggest that HAC is a very aggressive tumor with a generally poor prognosis.¹ Several studies have found that up to half of tumors locally recur despite aggressive surgical management, and metastasis occurs in 20% to 60% of patients.^3,8 However, a large study of US Surveillance, Epidemiology, and End Results data investigating the clinicopathologic characteristics of 289 patients with HAC revealed a more favorable prognosis.⁷ Mean overall survival and cancer-specific survival were greater than 13 years, and 10-year overall survival and cancer-specific survival rates were 60.2% and 90.5%, respectively.

Traditionally used to treat keratinocyte carcinomas, including basal cell carcinoma and squamous cell carcinoma, complete margin assessment with MMS is increasingly being utilized in the management of other cutaneous malignancies, including adnexal tumors.⁸ Due to its rarity, there remains no standard optimal treatment approach for HAC. One small retrospective study of 10 patients with HAC treated with MMS demonstrated favorable outcomes with no cases of recurrence, metastasis, or diseaserelated mortality in a mean 7-year follow-up period.⁹

Whole-body positron emission tomography/computed tomography performed in our patient approximately 1 month after MMS revealed mildly hypermetabolic left inguinal lymph nodes, which were thought to be reactive, and a question of small hypermetabolic foci in the liver. Follow-up computed tomography of the abdomen subsequently was performed and was negative for hepatic metastases. The patient will be monitored closely for local recurrence; however, the clearance of the tumor with MMS, which allowed complete margin assessment, is encouraging and supports MMS as superior to traditional surgical excision in the treatment of HAC. At his most recent examination 17 months after Mohs surgery, the patient remained tumor free.

Aggressive digital papillary adenocarcinoma (ADPA) is a rare malignant tumor originating in the sweat glands that can occur on the first toe but most commonly arises on the fingers. While both HAC and ADPA can manifest with an infiltrative growth pattern and cytologic atypia, ADPA classically reveals a well-circumscribed multinodular tumor in the dermis comprised of solid and cystic proliferation as well as papillary projections. In addition, ADPA has been described as having back-to-back glandular and ductal structures.¹⁰ Giant cell tumor of the tendon sheath is a benign fibrohistiocytic tumor that also typically manifests on the fingers but rarely can occur on the foot, including the first toe.^11,12 This tumor is more common in women and most frequently affects individuals aged 30 to 50 years.¹² Microscopically, giant cell tumor of the tendon sheath is characterized by a proliferation of osteoclastlike giant cells, epithelioid histiocytelike cells, mononuclear cells, and xanthomatous cells among collagenous bands.¹¹

Osteosarcoma is an uncommon tumor of osteoidproducing cells that usually arises in the metaphysis of long bones and manifests as a tender subcutaneous mass. It has a bimodal age distribution, peaking in adolescents and adults older than 65 years.¹³ While very rare, osteosarcoma has been reported to occur in the bones of the feet, including the phalanges.¹⁴ Given the recurrent nature of our patient’s tumor, metastasis should always be considered; however, in his case, full-body imaging was negative for additional malignancy.

THE DIAGNOSIS: Pemphigus Vegetans

Histopathologic examination of the biopsies from the scalp and left anterior thigh revealed suprabasal clefting with acantholytic cells extending into the follicular infundibulum with eosinophilic pustules within the epidermis. The dermis contained perivascular lymphohistiocytic and eosinophilic inflammatory infiltrates without viral cytopathic effects (Figure 1). Direct immunofluorescence revealed strong IgG and moderate IgA pericellular deposition around keratinocyte cytoplasms (Figure 2). Serologic evaluation demonstrated anti–desmoglein 3 antibodies. Based on the clinical presentation and histopathologic correlation, a diagnosis of pemphigus vegetans was made.

Pemphigus vegetans is a vesiculobullous autoimmune disease that is similar to pemphigus vulgaris but is characterized by the formation of vegetative plaques along the intertriginous areas and on the oral mucosa.¹ It is the rarest variant of all pemphigus subtypes and was first described by Neumann in 1876.² There are 2 subtypes of this variant: Hallopeau and Neumann, each with unique characteristics and physical manifestations. The Hallopeau type initially manifests with pustular lesions that rupture and evolve into erosions that commonly become infected. Gradually they merge and multiply to become more painful and vegetative.³ It has a more indolent course and typically responds well to treatment, and prolonged remission can be reached.⁴ The Neumann type is more severe and manifests with large vesiculobullous and erosive lesions that rupture and ulcerate, forming verrucous crusted vegetative plaques over the erosions.⁵ The erosions along the edge of the lesions induce new vegetation, becoming dry, hyperkeratotic, and fissured.³ The Neumann type often requires higher-dose steroids and typically is resistant to treatment.⁴ Patients can present with oral stomatitis and occasionally can develop a fissured or cerebriform appearance of the tongue, as seen in our patient (Figure 3).^1,2 Nail changes include onychorrhexis, onychomadesis, subungual pustules, and ultimately nail atrophy.⁵

Pemphigus diseases are characterized by IgG autoantibodies against desmoglein 3 and/or desmoglein 1. These are components of desmosomes that are responsible for keratinocyte adhesion, disruption of which results in the blister formation seen in pemphigus subtypes. The unique physical manifestation of pemphigus vegetans is thought to be due not only to autoantibodies against desmogleins 1 and 3 but also to autoantibodies against desmocollin 1 and 2.¹

Histopathologic examination reveals hyperkeratosis and pseudoepitheliomatous hyperplasia with acantholysis that creates a suprabasal cleft. Basal cells remain intact to the basement membrane by hemidesmosomes, resulting in a tombstone appearance. The Hallopeau type typically manifests with a large eosinophilic inflammatory response, leading to eosinophilic spongiosis and intraepidermal microabscesses. The Neumann type manifests with more of a neutrophilic and lymphocytic infiltrate, accompanied by the eosinophilic response.¹ For evaluation, obtain histopathology as well as direct immunofluorescence or enzyme-linked immunosorbent assay to look for intracellular deposition of desmoglein autoantibodies.

First-line treatment for pemphigus vulgaris and its variants is rituximab, an anti-CD20 monoclonal antibody. It has also been shown to have therapeutic benefit with combination of corticosteroids and rituximab. Corticosteroids should be given at a dose of 1 mg/kg daily for 2 to 4 weeks. Other immunosuppressive agents (steroid sparing) include azathioprine, dapsone, mycophenolate mofetil, methotrexate, cyclophosphamide, cyclosporine, and intravenous immunoglobulin. Pulse therapy with intermittent intravenous corticosteroids and immunosuppressants is another second-line therapeutic option. Topical therapeutic options include steroids, tacrolimus, and nicotinamide with oral tetracycline at onset and relapse. The goal of therapy is to maintain remission for 1 year then slowly taper treatment over another year.¹

Our patient initially was treated with prednisone, and subsequent courses of azathioprine and mycophenolate mofetil failed. He then was treated with 2 infusions of rituximab that were given 2 weeks apart. He was able to taper off the prednisone 1 month after the last infusion with complete remission of disease. He has been disease free for more than 9 months postinfusion.

Differential diagnoses for pemphigus vegetans can include bullous pemphigoid, bullous systemic lupus erythematosus, dermatitis herpetiformis, and pemphigus vulgaris. Lesion characteristics are key to differentiating pemphigus vegetans from other autoimmune blistering disorders. Bullous pemphigoid will manifest with tense blisters where pemphigus vulgaris will be flaccid; this is due to the difference in autoantibody targets between the conditions. Diagnosis depends on clinical presentation and histopathologic findings.

THE DIAGNOSIS: Pemphigus Vegetans

Histopathologic examination of the biopsies from the scalp and left anterior thigh revealed suprabasal clefting with acantholytic cells extending into the follicular infundibulum with eosinophilic pustules within the epidermis. The dermis contained perivascular lymphohistiocytic and eosinophilic inflammatory infiltrates without viral cytopathic effects (Figure 1). Direct immunofluorescence revealed strong IgG and moderate IgA pericellular deposition around keratinocyte cytoplasms (Figure 2). Serologic evaluation demonstrated anti–desmoglein 3 antibodies. Based on the clinical presentation and histopathologic correlation, a diagnosis of pemphigus vegetans was made.

Pemphigus vegetans is a vesiculobullous autoimmune disease that is similar to pemphigus vulgaris but is characterized by the formation of vegetative plaques along the intertriginous areas and on the oral mucosa.¹ It is the rarest variant of all pemphigus subtypes and was first described by Neumann in 1876.² There are 2 subtypes of this variant: Hallopeau and Neumann, each with unique characteristics and physical manifestations. The Hallopeau type initially manifests with pustular lesions that rupture and evolve into erosions that commonly become infected. Gradually they merge and multiply to become more painful and vegetative.³ It has a more indolent course and typically responds well to treatment, and prolonged remission can be reached.⁴ The Neumann type is more severe and manifests with large vesiculobullous and erosive lesions that rupture and ulcerate, forming verrucous crusted vegetative plaques over the erosions.⁵ The erosions along the edge of the lesions induce new vegetation, becoming dry, hyperkeratotic, and fissured.³ The Neumann type often requires higher-dose steroids and typically is resistant to treatment.⁴ Patients can present with oral stomatitis and occasionally can develop a fissured or cerebriform appearance of the tongue, as seen in our patient (Figure 3).^1,2 Nail changes include onychorrhexis, onychomadesis, subungual pustules, and ultimately nail atrophy.⁵

Pemphigus diseases are characterized by IgG autoantibodies against desmoglein 3 and/or desmoglein 1. These are components of desmosomes that are responsible for keratinocyte adhesion, disruption of which results in the blister formation seen in pemphigus subtypes. The unique physical manifestation of pemphigus vegetans is thought to be due not only to autoantibodies against desmogleins 1 and 3 but also to autoantibodies against desmocollin 1 and 2.¹

Histopathologic examination reveals hyperkeratosis and pseudoepitheliomatous hyperplasia with acantholysis that creates a suprabasal cleft. Basal cells remain intact to the basement membrane by hemidesmosomes, resulting in a tombstone appearance. The Hallopeau type typically manifests with a large eosinophilic inflammatory response, leading to eosinophilic spongiosis and intraepidermal microabscesses. The Neumann type manifests with more of a neutrophilic and lymphocytic infiltrate, accompanied by the eosinophilic response.¹ For evaluation, obtain histopathology as well as direct immunofluorescence or enzyme-linked immunosorbent assay to look for intracellular deposition of desmoglein autoantibodies.

First-line treatment for pemphigus vulgaris and its variants is rituximab, an anti-CD20 monoclonal antibody. It has also been shown to have therapeutic benefit with combination of corticosteroids and rituximab. Corticosteroids should be given at a dose of 1 mg/kg daily for 2 to 4 weeks. Other immunosuppressive agents (steroid sparing) include azathioprine, dapsone, mycophenolate mofetil, methotrexate, cyclophosphamide, cyclosporine, and intravenous immunoglobulin. Pulse therapy with intermittent intravenous corticosteroids and immunosuppressants is another second-line therapeutic option. Topical therapeutic options include steroids, tacrolimus, and nicotinamide with oral tetracycline at onset and relapse. The goal of therapy is to maintain remission for 1 year then slowly taper treatment over another year.¹

Our patient initially was treated with prednisone, and subsequent courses of azathioprine and mycophenolate mofetil failed. He then was treated with 2 infusions of rituximab that were given 2 weeks apart. He was able to taper off the prednisone 1 month after the last infusion with complete remission of disease. He has been disease free for more than 9 months postinfusion.

Differential diagnoses for pemphigus vegetans can include bullous pemphigoid, bullous systemic lupus erythematosus, dermatitis herpetiformis, and pemphigus vulgaris. Lesion characteristics are key to differentiating pemphigus vegetans from other autoimmune blistering disorders. Bullous pemphigoid will manifest with tense blisters where pemphigus vulgaris will be flaccid; this is due to the difference in autoantibody targets between the conditions. Diagnosis depends on clinical presentation and histopathologic findings.

THE DIAGNOSIS: Pemphigus Vegetans

Histopathologic examination of the biopsies from the scalp and left anterior thigh revealed suprabasal clefting with acantholytic cells extending into the follicular infundibulum with eosinophilic pustules within the epidermis. The dermis contained perivascular lymphohistiocytic and eosinophilic inflammatory infiltrates without viral cytopathic effects (Figure 1). Direct immunofluorescence revealed strong IgG and moderate IgA pericellular deposition around keratinocyte cytoplasms (Figure 2). Serologic evaluation demonstrated anti–desmoglein 3 antibodies. Based on the clinical presentation and histopathologic correlation, a diagnosis of pemphigus vegetans was made.

Pemphigus vegetans is a vesiculobullous autoimmune disease that is similar to pemphigus vulgaris but is characterized by the formation of vegetative plaques along the intertriginous areas and on the oral mucosa.¹ It is the rarest variant of all pemphigus subtypes and was first described by Neumann in 1876.² There are 2 subtypes of this variant: Hallopeau and Neumann, each with unique characteristics and physical manifestations. The Hallopeau type initially manifests with pustular lesions that rupture and evolve into erosions that commonly become infected. Gradually they merge and multiply to become more painful and vegetative.³ It has a more indolent course and typically responds well to treatment, and prolonged remission can be reached.⁴ The Neumann type is more severe and manifests with large vesiculobullous and erosive lesions that rupture and ulcerate, forming verrucous crusted vegetative plaques over the erosions.⁵ The erosions along the edge of the lesions induce new vegetation, becoming dry, hyperkeratotic, and fissured.³ The Neumann type often requires higher-dose steroids and typically is resistant to treatment.⁴ Patients can present with oral stomatitis and occasionally can develop a fissured or cerebriform appearance of the tongue, as seen in our patient (Figure 3).^1,2 Nail changes include onychorrhexis, onychomadesis, subungual pustules, and ultimately nail atrophy.⁵

Pemphigus diseases are characterized by IgG autoantibodies against desmoglein 3 and/or desmoglein 1. These are components of desmosomes that are responsible for keratinocyte adhesion, disruption of which results in the blister formation seen in pemphigus subtypes. The unique physical manifestation of pemphigus vegetans is thought to be due not only to autoantibodies against desmogleins 1 and 3 but also to autoantibodies against desmocollin 1 and 2.¹

Histopathologic examination reveals hyperkeratosis and pseudoepitheliomatous hyperplasia with acantholysis that creates a suprabasal cleft. Basal cells remain intact to the basement membrane by hemidesmosomes, resulting in a tombstone appearance. The Hallopeau type typically manifests with a large eosinophilic inflammatory response, leading to eosinophilic spongiosis and intraepidermal microabscesses. The Neumann type manifests with more of a neutrophilic and lymphocytic infiltrate, accompanied by the eosinophilic response.¹ For evaluation, obtain histopathology as well as direct immunofluorescence or enzyme-linked immunosorbent assay to look for intracellular deposition of desmoglein autoantibodies.

First-line treatment for pemphigus vulgaris and its variants is rituximab, an anti-CD20 monoclonal antibody. It has also been shown to have therapeutic benefit with combination of corticosteroids and rituximab. Corticosteroids should be given at a dose of 1 mg/kg daily for 2 to 4 weeks. Other immunosuppressive agents (steroid sparing) include azathioprine, dapsone, mycophenolate mofetil, methotrexate, cyclophosphamide, cyclosporine, and intravenous immunoglobulin. Pulse therapy with intermittent intravenous corticosteroids and immunosuppressants is another second-line therapeutic option. Topical therapeutic options include steroids, tacrolimus, and nicotinamide with oral tetracycline at onset and relapse. The goal of therapy is to maintain remission for 1 year then slowly taper treatment over another year.¹

Our patient initially was treated with prednisone, and subsequent courses of azathioprine and mycophenolate mofetil failed. He then was treated with 2 infusions of rituximab that were given 2 weeks apart. He was able to taper off the prednisone 1 month after the last infusion with complete remission of disease. He has been disease free for more than 9 months postinfusion.

Differential diagnoses for pemphigus vegetans can include bullous pemphigoid, bullous systemic lupus erythematosus, dermatitis herpetiformis, and pemphigus vulgaris. Lesion characteristics are key to differentiating pemphigus vegetans from other autoimmune blistering disorders. Bullous pemphigoid will manifest with tense blisters where pemphigus vulgaris will be flaccid; this is due to the difference in autoantibody targets between the conditions. Diagnosis depends on clinical presentation and histopathologic findings.

There is a direct link between psoriasis and metabolic conditions such as diabetes mellitus and obesity.¹ Exercise of varied intensity in patients with chronic inflammatory and metabolic conditions can help improve quality of life and severity of disease; however, there has not been a clear consensus on the recommended duration and types of exercise that are most advantageous.^1-5 We reviewed the literature to identify physical and mental health impacts of exercise on patients with psoriasis, and we present the recommended duration and types of exercise that are most impactful for these patients.

One indicator of the link between psoriasis and exercise is the level of peroxisome proliferator activated receptor gamma coactivator-1 α (PGC-1α) in muscle cells.² This marker reduces inflammation. When levels are low in muscle cells, an induction occurs that leads to systemic or local inflammation; however, skeletal muscle PGC-1α levels increase following exercise, indicating reduced inflammation.² The level of PGC-1α is measured through muscle biopsy and polymerase chain reaction.⁶ Another indicator of the correlation between exercise and inflammation is lipoprotein-associated phospholipase A2, which is produced by inflammatory cells and has a correlation with cardiovascular disease. Exercise reduces lipoprotein-associated phospholipase A2 levels, and a sedentary lifestyle correlates with increased levels of this marker.³ Lipoprotein-associated phospholipase A2 is measured through an enzyme-linked immunosorbent assay of the blood, with levels around 200 ng/mL considered high.⁷ Patients with psoriasis are 30% less likely to participate in physical activity compared to patients without psoriasis, which can be attributed to psychosocial impairment and other factors. Sedentary lifestyle is associated with new or worsening metabolic disease and prevalence of psoriatic lesions.¹

A metabolic equivalent task score is a classification system that measures the rate of the body’s oxygen uptake for any given activity.⁴ A score of 20.9 or more metabolic equivalent task hours of vigorous exercise per week—equal to 105 minutes of running or 180 minutes of swimming or playing tennis—is linked with a 25% to 30% risk reduction of psoriasis in women.⁴ Therefore, we recommend 30 minutes of exercise 4 to 5 times per week for women. These periods of exercise should consist mainly of activities that will not cause psoriasis flares due to excessive sweating, skin trauma, or prolonged sun exposure.⁵ Walking, yoga, and bike riding all could be good exercise options for those with psoriasis. The National Psoriasis Foundation offers guidance on physical activity in patients with psoriasis or psoriatic arthritis.⁸ Psoriasis has apparent physical and psychosocial impacts on patients that can be prevented and improved through the exercise recommendations presented in this article. Dermatologists should use these recommendations to address psoriasis in their everyday practice.

There is a direct link between psoriasis and metabolic conditions such as diabetes mellitus and obesity.¹ Exercise of varied intensity in patients with chronic inflammatory and metabolic conditions can help improve quality of life and severity of disease; however, there has not been a clear consensus on the recommended duration and types of exercise that are most advantageous.^1-5 We reviewed the literature to identify physical and mental health impacts of exercise on patients with psoriasis, and we present the recommended duration and types of exercise that are most impactful for these patients.

One indicator of the link between psoriasis and exercise is the level of peroxisome proliferator activated receptor gamma coactivator-1 α (PGC-1α) in muscle cells.² This marker reduces inflammation. When levels are low in muscle cells, an induction occurs that leads to systemic or local inflammation; however, skeletal muscle PGC-1α levels increase following exercise, indicating reduced inflammation.² The level of PGC-1α is measured through muscle biopsy and polymerase chain reaction.⁶ Another indicator of the correlation between exercise and inflammation is lipoprotein-associated phospholipase A2, which is produced by inflammatory cells and has a correlation with cardiovascular disease. Exercise reduces lipoprotein-associated phospholipase A2 levels, and a sedentary lifestyle correlates with increased levels of this marker.³ Lipoprotein-associated phospholipase A2 is measured through an enzyme-linked immunosorbent assay of the blood, with levels around 200 ng/mL considered high.⁷ Patients with psoriasis are 30% less likely to participate in physical activity compared to patients without psoriasis, which can be attributed to psychosocial impairment and other factors. Sedentary lifestyle is associated with new or worsening metabolic disease and prevalence of psoriatic lesions.¹

A metabolic equivalent task score is a classification system that measures the rate of the body’s oxygen uptake for any given activity.⁴ A score of 20.9 or more metabolic equivalent task hours of vigorous exercise per week—equal to 105 minutes of running or 180 minutes of swimming or playing tennis—is linked with a 25% to 30% risk reduction of psoriasis in women.⁴ Therefore, we recommend 30 minutes of exercise 4 to 5 times per week for women. These periods of exercise should consist mainly of activities that will not cause psoriasis flares due to excessive sweating, skin trauma, or prolonged sun exposure.⁵ Walking, yoga, and bike riding all could be good exercise options for those with psoriasis. The National Psoriasis Foundation offers guidance on physical activity in patients with psoriasis or psoriatic arthritis.⁸ Psoriasis has apparent physical and psychosocial impacts on patients that can be prevented and improved through the exercise recommendations presented in this article. Dermatologists should use these recommendations to address psoriasis in their everyday practice.

There is a direct link between psoriasis and metabolic conditions such as diabetes mellitus and obesity.¹ Exercise of varied intensity in patients with chronic inflammatory and metabolic conditions can help improve quality of life and severity of disease; however, there has not been a clear consensus on the recommended duration and types of exercise that are most advantageous.^1-5 We reviewed the literature to identify physical and mental health impacts of exercise on patients with psoriasis, and we present the recommended duration and types of exercise that are most impactful for these patients.

One indicator of the link between psoriasis and exercise is the level of peroxisome proliferator activated receptor gamma coactivator-1 α (PGC-1α) in muscle cells.² This marker reduces inflammation. When levels are low in muscle cells, an induction occurs that leads to systemic or local inflammation; however, skeletal muscle PGC-1α levels increase following exercise, indicating reduced inflammation.² The level of PGC-1α is measured through muscle biopsy and polymerase chain reaction.⁶ Another indicator of the correlation between exercise and inflammation is lipoprotein-associated phospholipase A2, which is produced by inflammatory cells and has a correlation with cardiovascular disease. Exercise reduces lipoprotein-associated phospholipase A2 levels, and a sedentary lifestyle correlates with increased levels of this marker.³ Lipoprotein-associated phospholipase A2 is measured through an enzyme-linked immunosorbent assay of the blood, with levels around 200 ng/mL considered high.⁷ Patients with psoriasis are 30% less likely to participate in physical activity compared to patients without psoriasis, which can be attributed to psychosocial impairment and other factors. Sedentary lifestyle is associated with new or worsening metabolic disease and prevalence of psoriatic lesions.¹

A metabolic equivalent task score is a classification system that measures the rate of the body’s oxygen uptake for any given activity.⁴ A score of 20.9 or more metabolic equivalent task hours of vigorous exercise per week—equal to 105 minutes of running or 180 minutes of swimming or playing tennis—is linked with a 25% to 30% risk reduction of psoriasis in women.⁴ Therefore, we recommend 30 minutes of exercise 4 to 5 times per week for women. These periods of exercise should consist mainly of activities that will not cause psoriasis flares due to excessive sweating, skin trauma, or prolonged sun exposure.⁵ Walking, yoga, and bike riding all could be good exercise options for those with psoriasis. The National Psoriasis Foundation offers guidance on physical activity in patients with psoriasis or psoriatic arthritis.⁸ Psoriasis has apparent physical and psychosocial impacts on patients that can be prevented and improved through the exercise recommendations presented in this article. Dermatologists should use these recommendations to address psoriasis in their everyday practice.

THE DIAGNOSIS: Fixed Drug Eruption

Based on the patient’s clinical presentation and history of similar eruptions, a diagnosis of levofloxacin-induced fixed drug eruption (FDE) was made. After cessation of the drug, the lesions resolved within 1 week without any residual postinflammatory hyperpigmentation.

Fixed drug eruption is an adverse cutaneous reaction characterized by the onset of a rash at a fixed location each time a specific medication is administered. Patients typically report a history of similar eruptions, often involving the upper and lower extremities, genital area, or mucous membranes. The most common causative agents vary, but retrospective analyses primarily implicate nonsteroidal anti-inflammatory drugs followed by antibiotics (eg, amoxicillin, levofloxacin, doxycycline) and antiepileptics.^1,2

While FDE can be solitary or scattered, most patients have 5 or fewer lesions, with a mean interval of 48 hours from exposure to the causative agent to onset of the rash.¹ The lesions can be differentiated by their typically solitary, well-demarcated, round or oval appearance; they also are erythematous to purple with a dusky center. The lesions may increase in size and number with each additional exposure to the offending medication.^1,3 Postinflammatory hyperpigmentation may last for weeks to months after the acute inflammatory response has resolved.

The high risk for recurrence of FDE may be explained by the presence of tissue resident memory T (TRM) cells in the affected skin that evoke a characteristic clinical manifestation upon administration of a causative agent.^2,3 Intraepidermal CD8⁺ TRM cells, which have an effectormemory phenotype, may contribute to the development of localized tissue damage; these cells demonstrate their effector function by the rapid increase in interferon gamma after challenge.² Within 24 hours of administration of the offending medication, CD8⁺ TRM cells migrate upward in the epidermis, and their activity leads to the epidermal necrosis observed with FDE. The self-limiting nature of FDE can be explained by the action of CD4+ Foxp3+ regulatory T cells that migrate similarly and induce the production of IL-10, which limits the damage inflicted by the CD8⁺ T cells.¹

Type I hypersensitivity reactions are IgE mediated; typically occur much more rapidly than FDE; and involve a raised urticarial rash, pruritus, and flushing. Urticaria is useful in identifying IgE-mediated reactions and mast cell degranulation. Previous exposure to the drug in question is required for diagnosis.⁴

Type IV delayed hypersensitivity reactions—including contact dermatitis and FDE—are mediated by T cells rather than IgE. These reactions occur at least 48 to 72 hours after drug exposure.⁴ Contact dermatitis follows exposure to an irritant but generally is limited to the site of contact and manifests with burning or stinging. Chronic contact dermatitis is characterized by erythema, scaling, and lichenification that may be associated with burning pain.

The target lesions of erythema multiforme are associated with the use of medications such as nonsteroidal anti-inflammatory drugs, antiepileptics, and antibiotics in fewer than 10% of cases. Infections are the predominant cause, with herpes simplex virus 1 being the most common etiology.⁵ Erythema multiforme lesions have 3 concentric segments: a dark red inflammatory zone surrounded by a pale ring of edema, both of which are surrounded by an erythematous halo. Lesions initially are distributed symmetrically on the extensor surfaces of the upper and lower extremities, but mucosal involvement may be present.⁵

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, involves fever and peripheral neutrophilia in addition to cutaneous erythematous eruptions and dermal neutrophilic infiltration on histopathology.⁶ Most cases are idiopathic but may occur in the setting of malignancy or drug administration. A major criterion for drug-induced Sweet syndrome is abrupt onset of painful erythematous plaques or nodules with pyrexia.⁶

THE DIAGNOSIS: Fixed Drug Eruption

Based on the patient’s clinical presentation and history of similar eruptions, a diagnosis of levofloxacin-induced fixed drug eruption (FDE) was made. After cessation of the drug, the lesions resolved within 1 week without any residual postinflammatory hyperpigmentation.

Fixed drug eruption is an adverse cutaneous reaction characterized by the onset of a rash at a fixed location each time a specific medication is administered. Patients typically report a history of similar eruptions, often involving the upper and lower extremities, genital area, or mucous membranes. The most common causative agents vary, but retrospective analyses primarily implicate nonsteroidal anti-inflammatory drugs followed by antibiotics (eg, amoxicillin, levofloxacin, doxycycline) and antiepileptics.^1,2

While FDE can be solitary or scattered, most patients have 5 or fewer lesions, with a mean interval of 48 hours from exposure to the causative agent to onset of the rash.¹ The lesions can be differentiated by their typically solitary, well-demarcated, round or oval appearance; they also are erythematous to purple with a dusky center. The lesions may increase in size and number with each additional exposure to the offending medication.^1,3 Postinflammatory hyperpigmentation may last for weeks to months after the acute inflammatory response has resolved.

The high risk for recurrence of FDE may be explained by the presence of tissue resident memory T (TRM) cells in the affected skin that evoke a characteristic clinical manifestation upon administration of a causative agent.^2,3 Intraepidermal CD8⁺ TRM cells, which have an effectormemory phenotype, may contribute to the development of localized tissue damage; these cells demonstrate their effector function by the rapid increase in interferon gamma after challenge.² Within 24 hours of administration of the offending medication, CD8⁺ TRM cells migrate upward in the epidermis, and their activity leads to the epidermal necrosis observed with FDE. The self-limiting nature of FDE can be explained by the action of CD4+ Foxp3+ regulatory T cells that migrate similarly and induce the production of IL-10, which limits the damage inflicted by the CD8⁺ T cells.¹

Type I hypersensitivity reactions are IgE mediated; typically occur much more rapidly than FDE; and involve a raised urticarial rash, pruritus, and flushing. Urticaria is useful in identifying IgE-mediated reactions and mast cell degranulation. Previous exposure to the drug in question is required for diagnosis.⁴

Type IV delayed hypersensitivity reactions—including contact dermatitis and FDE—are mediated by T cells rather than IgE. These reactions occur at least 48 to 72 hours after drug exposure.⁴ Contact dermatitis follows exposure to an irritant but generally is limited to the site of contact and manifests with burning or stinging. Chronic contact dermatitis is characterized by erythema, scaling, and lichenification that may be associated with burning pain.

The target lesions of erythema multiforme are associated with the use of medications such as nonsteroidal anti-inflammatory drugs, antiepileptics, and antibiotics in fewer than 10% of cases. Infections are the predominant cause, with herpes simplex virus 1 being the most common etiology.⁵ Erythema multiforme lesions have 3 concentric segments: a dark red inflammatory zone surrounded by a pale ring of edema, both of which are surrounded by an erythematous halo. Lesions initially are distributed symmetrically on the extensor surfaces of the upper and lower extremities, but mucosal involvement may be present.⁵

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, involves fever and peripheral neutrophilia in addition to cutaneous erythematous eruptions and dermal neutrophilic infiltration on histopathology.⁶ Most cases are idiopathic but may occur in the setting of malignancy or drug administration. A major criterion for drug-induced Sweet syndrome is abrupt onset of painful erythematous plaques or nodules with pyrexia.⁶

THE DIAGNOSIS: Fixed Drug Eruption

Based on the patient’s clinical presentation and history of similar eruptions, a diagnosis of levofloxacin-induced fixed drug eruption (FDE) was made. After cessation of the drug, the lesions resolved within 1 week without any residual postinflammatory hyperpigmentation.

Fixed drug eruption is an adverse cutaneous reaction characterized by the onset of a rash at a fixed location each time a specific medication is administered. Patients typically report a history of similar eruptions, often involving the upper and lower extremities, genital area, or mucous membranes. The most common causative agents vary, but retrospective analyses primarily implicate nonsteroidal anti-inflammatory drugs followed by antibiotics (eg, amoxicillin, levofloxacin, doxycycline) and antiepileptics.^1,2

While FDE can be solitary or scattered, most patients have 5 or fewer lesions, with a mean interval of 48 hours from exposure to the causative agent to onset of the rash.¹ The lesions can be differentiated by their typically solitary, well-demarcated, round or oval appearance; they also are erythematous to purple with a dusky center. The lesions may increase in size and number with each additional exposure to the offending medication.^1,3 Postinflammatory hyperpigmentation may last for weeks to months after the acute inflammatory response has resolved.

The high risk for recurrence of FDE may be explained by the presence of tissue resident memory T (TRM) cells in the affected skin that evoke a characteristic clinical manifestation upon administration of a causative agent.^2,3 Intraepidermal CD8⁺ TRM cells, which have an effectormemory phenotype, may contribute to the development of localized tissue damage; these cells demonstrate their effector function by the rapid increase in interferon gamma after challenge.² Within 24 hours of administration of the offending medication, CD8⁺ TRM cells migrate upward in the epidermis, and their activity leads to the epidermal necrosis observed with FDE. The self-limiting nature of FDE can be explained by the action of CD4+ Foxp3+ regulatory T cells that migrate similarly and induce the production of IL-10, which limits the damage inflicted by the CD8⁺ T cells.¹

Type I hypersensitivity reactions are IgE mediated; typically occur much more rapidly than FDE; and involve a raised urticarial rash, pruritus, and flushing. Urticaria is useful in identifying IgE-mediated reactions and mast cell degranulation. Previous exposure to the drug in question is required for diagnosis.⁴

Type IV delayed hypersensitivity reactions—including contact dermatitis and FDE—are mediated by T cells rather than IgE. These reactions occur at least 48 to 72 hours after drug exposure.⁴ Contact dermatitis follows exposure to an irritant but generally is limited to the site of contact and manifests with burning or stinging. Chronic contact dermatitis is characterized by erythema, scaling, and lichenification that may be associated with burning pain.

The target lesions of erythema multiforme are associated with the use of medications such as nonsteroidal anti-inflammatory drugs, antiepileptics, and antibiotics in fewer than 10% of cases. Infections are the predominant cause, with herpes simplex virus 1 being the most common etiology.⁵ Erythema multiforme lesions have 3 concentric segments: a dark red inflammatory zone surrounded by a pale ring of edema, both of which are surrounded by an erythematous halo. Lesions initially are distributed symmetrically on the extensor surfaces of the upper and lower extremities, but mucosal involvement may be present.⁵

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, involves fever and peripheral neutrophilia in addition to cutaneous erythematous eruptions and dermal neutrophilic infiltration on histopathology.⁶ Most cases are idiopathic but may occur in the setting of malignancy or drug administration. A major criterion for drug-induced Sweet syndrome is abrupt onset of painful erythematous plaques or nodules with pyrexia.⁶