Article

Despite multiple existing conventional synthetic disease-modifying antirheumatic drug (csDMARD) and biologic DMARD (bDMARD) options, many patients with rheumatoid arthritis (RA) do not respond adequately to treatment. In an exciting development, a recent phase 2 study by Tuttle and colleagues examined a novel treatment approach in RA: stimulation of the programmed cell death protein 1 (PD-1) inhibitor pathway. PD-1 is a checkpoint inhibitor receptor whose activation reflects T-cell activation and may play a role in synovitis and extra-articular inflammation. Blocking PD-1 in cancer therapy has been associated with an increase in inflammatory arthritis. In this 12-week study, RA disease activity was analyzed in patients randomly assigned to two different monthly intravenous doses of peresolimab or placebo. Of note, a large majority of participants were seropositive for rheumatoid factor (RF) or cyclic citrullinated peptide (CCP). Patients receiving the 700-mg dose of peresolimab had a better American College of Rheumatology (ACR) 20 response than did those receiving placebo (71% vs 42%), but not a better ACR50 or ACR70 response; the 300-mg dose was not better than placebo. Although reported adverse events were similar in all three groups, with a short timeframe it would be difficult to address concerns about cancer risk. Though this novel treatment is exciting, a larger and longer-term trial is necessary to address this concern as well as potentially tease out risk factors (including age or other immunosuppression) in this susceptible group.

Two other studies examined use of a much older csDMARD therapy, hydroxychloroquine (HCQ), in Brazilian patients with RA. Bredemeier and colleagues looked at the effects of HCQ on adverse events as well as the persistence of bDMARD/targeted synthetic DMARD (tsDMARD) therapy in over 1300 patients with RA. Using the BiobadaBrasil registry of patients starting their first bDMARD or Janus kinase (JAK) inhibitor, they looked at effects of combination therapy with HCQ during the treatment course of up to six bDMARD or JAK inhibitors. At baseline, patients prescribed antimalarial therapy had shorter RA duration and began treatment earlier, perhaps due to patient or physician preferences regarding starting "milder" antimalarial medication earlier or due to use of "triple therapy" with methotrexate and sulfasalazine. Of interest, patients receiving antimalarial therapy had a lower incidence of adverse events, especially serious infections, but no effect on cardiovascular events was seen despite HCQ's perceived beneficial effects on thrombotic risk and cholesterol profile. Patients receiving HCQ were also more likely to persist in their course of bDMARD or JAK inhibitor therapy, though the effect size seems relatively small. As the focus in this study was on adverse effects, the authors' analysis of the effects on antimalarials on the persistence of therapy was not detailed.

Lin and colleagues also looked at the effects of HCQ in patients with older-onset RA with respect to mortality risk. Using data from the electronic health records of a hospital in Taiwan, mortality-associated risk factors were evaluated in 980 patients with RA diagnosed at >60 years. Male sex, current smoking status, and cancer status were all associated with mortality, whereas HCQ use was associated with reduced mortality (hazard ratio 0.30). In contrast to the registry study mentioned above, patients receiving HCQ had a lower risk for cardiovascular events, hyperlipidemia, diabetes, and chronic kidney disease. Interaction with cancer was less clear due to lower number of patients. Of interest, use of cyclosporine, leflunomide, and a bDMARD was associated with higher mortality risk. The source and true relevance of the potential risk reduction in this study is not clear because of the lack of prospective data, but combined with the information above, this study suggests that the benefits of HCQ use should not be discounted in patients with RA.

Despite multiple existing conventional synthetic disease-modifying antirheumatic drug (csDMARD) and biologic DMARD (bDMARD) options, many patients with rheumatoid arthritis (RA) do not respond adequately to treatment. In an exciting development, a recent phase 2 study by Tuttle and colleagues examined a novel treatment approach in RA: stimulation of the programmed cell death protein 1 (PD-1) inhibitor pathway. PD-1 is a checkpoint inhibitor receptor whose activation reflects T-cell activation and may play a role in synovitis and extra-articular inflammation. Blocking PD-1 in cancer therapy has been associated with an increase in inflammatory arthritis. In this 12-week study, RA disease activity was analyzed in patients randomly assigned to two different monthly intravenous doses of peresolimab or placebo. Of note, a large majority of participants were seropositive for rheumatoid factor (RF) or cyclic citrullinated peptide (CCP). Patients receiving the 700-mg dose of peresolimab had a better American College of Rheumatology (ACR) 20 response than did those receiving placebo (71% vs 42%), but not a better ACR50 or ACR70 response; the 300-mg dose was not better than placebo. Although reported adverse events were similar in all three groups, with a short timeframe it would be difficult to address concerns about cancer risk. Though this novel treatment is exciting, a larger and longer-term trial is necessary to address this concern as well as potentially tease out risk factors (including age or other immunosuppression) in this susceptible group.

Two other studies examined use of a much older csDMARD therapy, hydroxychloroquine (HCQ), in Brazilian patients with RA. Bredemeier and colleagues looked at the effects of HCQ on adverse events as well as the persistence of bDMARD/targeted synthetic DMARD (tsDMARD) therapy in over 1300 patients with RA. Using the BiobadaBrasil registry of patients starting their first bDMARD or Janus kinase (JAK) inhibitor, they looked at effects of combination therapy with HCQ during the treatment course of up to six bDMARD or JAK inhibitors. At baseline, patients prescribed antimalarial therapy had shorter RA duration and began treatment earlier, perhaps due to patient or physician preferences regarding starting "milder" antimalarial medication earlier or due to use of "triple therapy" with methotrexate and sulfasalazine. Of interest, patients receiving antimalarial therapy had a lower incidence of adverse events, especially serious infections, but no effect on cardiovascular events was seen despite HCQ's perceived beneficial effects on thrombotic risk and cholesterol profile. Patients receiving HCQ were also more likely to persist in their course of bDMARD or JAK inhibitor therapy, though the effect size seems relatively small. As the focus in this study was on adverse effects, the authors' analysis of the effects on antimalarials on the persistence of therapy was not detailed.

Lin and colleagues also looked at the effects of HCQ in patients with older-onset RA with respect to mortality risk. Using data from the electronic health records of a hospital in Taiwan, mortality-associated risk factors were evaluated in 980 patients with RA diagnosed at >60 years. Male sex, current smoking status, and cancer status were all associated with mortality, whereas HCQ use was associated with reduced mortality (hazard ratio 0.30). In contrast to the registry study mentioned above, patients receiving HCQ had a lower risk for cardiovascular events, hyperlipidemia, diabetes, and chronic kidney disease. Interaction with cancer was less clear due to lower number of patients. Of interest, use of cyclosporine, leflunomide, and a bDMARD was associated with higher mortality risk. The source and true relevance of the potential risk reduction in this study is not clear because of the lack of prospective data, but combined with the information above, this study suggests that the benefits of HCQ use should not be discounted in patients with RA.

Despite multiple existing conventional synthetic disease-modifying antirheumatic drug (csDMARD) and biologic DMARD (bDMARD) options, many patients with rheumatoid arthritis (RA) do not respond adequately to treatment. In an exciting development, a recent phase 2 study by Tuttle and colleagues examined a novel treatment approach in RA: stimulation of the programmed cell death protein 1 (PD-1) inhibitor pathway. PD-1 is a checkpoint inhibitor receptor whose activation reflects T-cell activation and may play a role in synovitis and extra-articular inflammation. Blocking PD-1 in cancer therapy has been associated with an increase in inflammatory arthritis. In this 12-week study, RA disease activity was analyzed in patients randomly assigned to two different monthly intravenous doses of peresolimab or placebo. Of note, a large majority of participants were seropositive for rheumatoid factor (RF) or cyclic citrullinated peptide (CCP). Patients receiving the 700-mg dose of peresolimab had a better American College of Rheumatology (ACR) 20 response than did those receiving placebo (71% vs 42%), but not a better ACR50 or ACR70 response; the 300-mg dose was not better than placebo. Although reported adverse events were similar in all three groups, with a short timeframe it would be difficult to address concerns about cancer risk. Though this novel treatment is exciting, a larger and longer-term trial is necessary to address this concern as well as potentially tease out risk factors (including age or other immunosuppression) in this susceptible group.

Two other studies examined use of a much older csDMARD therapy, hydroxychloroquine (HCQ), in Brazilian patients with RA. Bredemeier and colleagues looked at the effects of HCQ on adverse events as well as the persistence of bDMARD/targeted synthetic DMARD (tsDMARD) therapy in over 1300 patients with RA. Using the BiobadaBrasil registry of patients starting their first bDMARD or Janus kinase (JAK) inhibitor, they looked at effects of combination therapy with HCQ during the treatment course of up to six bDMARD or JAK inhibitors. At baseline, patients prescribed antimalarial therapy had shorter RA duration and began treatment earlier, perhaps due to patient or physician preferences regarding starting "milder" antimalarial medication earlier or due to use of "triple therapy" with methotrexate and sulfasalazine. Of interest, patients receiving antimalarial therapy had a lower incidence of adverse events, especially serious infections, but no effect on cardiovascular events was seen despite HCQ's perceived beneficial effects on thrombotic risk and cholesterol profile. Patients receiving HCQ were also more likely to persist in their course of bDMARD or JAK inhibitor therapy, though the effect size seems relatively small. As the focus in this study was on adverse effects, the authors' analysis of the effects on antimalarials on the persistence of therapy was not detailed.

Lin and colleagues also looked at the effects of HCQ in patients with older-onset RA with respect to mortality risk. Using data from the electronic health records of a hospital in Taiwan, mortality-associated risk factors were evaluated in 980 patients with RA diagnosed at >60 years. Male sex, current smoking status, and cancer status were all associated with mortality, whereas HCQ use was associated with reduced mortality (hazard ratio 0.30). In contrast to the registry study mentioned above, patients receiving HCQ had a lower risk for cardiovascular events, hyperlipidemia, diabetes, and chronic kidney disease. Interaction with cancer was less clear due to lower number of patients. Of interest, use of cyclosporine, leflunomide, and a bDMARD was associated with higher mortality risk. The source and true relevance of the potential risk reduction in this study is not clear because of the lack of prospective data, but combined with the information above, this study suggests that the benefits of HCQ use should not be discounted in patients with RA.

After a median follow-up of 21.6 mo, the dalpiciclib group demonstrated a significantly longer median progression-free survival (PFS) compared with the placebo group (30.6 mo vs 18.2 mo; stratified hazard ratio [HR] 0.51; 95% CI 0.38-0.69; P < .0001). Overall, the dalpiciclib group demonstrated a manageable safety profile, although a higher percentage of grade 3/4 adverse events was noted with dalpiciclib than with placebo (90% vs 12%), as expected. Overall survival data for this CDK4/6 inhibitor are yet to come. These results suggest that dalpiciclib in combination with endocrine therapy is an alternative treatment for this group of patients, especially in countries where the traditionally approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are not available.

The optimal sequencing of endocrine therapy (ET) after progression on CDK4/6 inhibitor–based therapy remains a challenge. In the phase 2 MAINTAIN trial, 119 patients (all of whom had HR+/HER2- metastatic breast cancer and who progressed on ET and CDK4/6 inhibitors) were randomly assigned to receive a different ET (fulvestrant or exemestane) from the previous ET they had received plus either the CDK4/6 inhibitor ribociclib or placebo. In the study by Kalinksky and colleagues, at a median follow-up of 18.2 mo, a significant improvement in PFS was observed in the switched ET-plus-ribociclib group compared with the switched ET-plus-placebo group (HR 0.57; P = .006). The phase 2 MAINTAIN trial is the first randomized trial to show the benefit of a CDK4/6 inhibitor after progression on another CDK4/6 inhibitor. It is important to note that the majority of patients in the MAINTAIN study previously received palbociclib in the first-line setting, which in recent studies has been demonstrated to be inferior to other CDK4/6 inhibitors. Therefore, it is important to confirm whether this will hold true upon progression from ribociclib or abemaciclib in the first-line setting. In addition, more data are needed to compare this approach with other ET treatment options, such as phosphoinositide 3-kinases inhibitors and oral selective estrogen receptor degraders.

There are several options for adjuvant radiation therapy for early-stage breast cancer. A meta-analysis of 14 randomized controlled trials and six comparative observational studies assessed the efficacy of whole breast irradiation (WBI) compared with partial breast irradiation (PBI) in 17,234 adults with early-stage breast cancer. Results of this meta-analysis showed that PBI was not significantly different from WBI, with similar rates of ipsilateral breast recurrence  at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91), although patients undergoing PBI reported fewer acute adverse events  compared with patients undergoing WBI (incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 adverse events (IRR 0.21; 95% CI 0.07-0.62). These findings support using PBI as the adjuvant radiotherapy modality for select patients with favorable-risk early-stage breast cancer.

Another meta-analysis looked at assessing the survival benefit of adding CDK4/6 inhibitors to standard ET in older patients with advanced breast cancer. The study included 10 trials with 1985 older patients with advanced ER+ breast cancer who received ET with or without CDK4/6 inhibitors. The findings showed that adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (HR 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients (age ≥ 65 years) with advanced breast cancer. Grade 3-4 neutropenia and diarrhea were similar in older patients. This study supports the use of CDK4/6 inhibitors as a reasonable treatment modality for older patients. More studies dedicated to the geriatric population are needed to help elaborate on the efficacy and tolerability of such agents in this population.

The phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 (NSABP B-42) trial evaluated the role of extended letrozole therapy in postmenopausal breast cancer patients who were disease-free after 5 years of aromatase inhibitor–based therapy. The study included 3966 postmenopausal women with stage I-IIIA HR+ breast cancer who were randomly assigned to receive letrozole or placebo for 5 more years. After a median follow-up of 10.3 years, letrozole significantly improved disease-free survival (10-year absolute benefit 3.4%; HR 0.85; P = .01) compared with placebo, although there were no differences noted in overall survival between the groups (HR 0.97, P = .74). Furthermore, letrozole significantly reduced the breast cancer–free interval (HR 0.75, ,P = .003) and distant recurrence (HR 0.72, P = .01). There were no notable differences in toxicity, particularly rates of osteoporotic fractures and arterial thrombotic events, between the groups. Extended therapy with aromatase inhibitors beyond 5 years can be considered for select patients with early-stage breast cancer. Careful consideration of risks and benefits is needed to make these recommendations. 

After a median follow-up of 21.6 mo, the dalpiciclib group demonstrated a significantly longer median progression-free survival (PFS) compared with the placebo group (30.6 mo vs 18.2 mo; stratified hazard ratio [HR] 0.51; 95% CI 0.38-0.69; P < .0001). Overall, the dalpiciclib group demonstrated a manageable safety profile, although a higher percentage of grade 3/4 adverse events was noted with dalpiciclib than with placebo (90% vs 12%), as expected. Overall survival data for this CDK4/6 inhibitor are yet to come. These results suggest that dalpiciclib in combination with endocrine therapy is an alternative treatment for this group of patients, especially in countries where the traditionally approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are not available.

The optimal sequencing of endocrine therapy (ET) after progression on CDK4/6 inhibitor–based therapy remains a challenge. In the phase 2 MAINTAIN trial, 119 patients (all of whom had HR+/HER2- metastatic breast cancer and who progressed on ET and CDK4/6 inhibitors) were randomly assigned to receive a different ET (fulvestrant or exemestane) from the previous ET they had received plus either the CDK4/6 inhibitor ribociclib or placebo. In the study by Kalinksky and colleagues, at a median follow-up of 18.2 mo, a significant improvement in PFS was observed in the switched ET-plus-ribociclib group compared with the switched ET-plus-placebo group (HR 0.57; P = .006). The phase 2 MAINTAIN trial is the first randomized trial to show the benefit of a CDK4/6 inhibitor after progression on another CDK4/6 inhibitor. It is important to note that the majority of patients in the MAINTAIN study previously received palbociclib in the first-line setting, which in recent studies has been demonstrated to be inferior to other CDK4/6 inhibitors. Therefore, it is important to confirm whether this will hold true upon progression from ribociclib or abemaciclib in the first-line setting. In addition, more data are needed to compare this approach with other ET treatment options, such as phosphoinositide 3-kinases inhibitors and oral selective estrogen receptor degraders.

There are several options for adjuvant radiation therapy for early-stage breast cancer. A meta-analysis of 14 randomized controlled trials and six comparative observational studies assessed the efficacy of whole breast irradiation (WBI) compared with partial breast irradiation (PBI) in 17,234 adults with early-stage breast cancer. Results of this meta-analysis showed that PBI was not significantly different from WBI, with similar rates of ipsilateral breast recurrence  at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91), although patients undergoing PBI reported fewer acute adverse events  compared with patients undergoing WBI (incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 adverse events (IRR 0.21; 95% CI 0.07-0.62). These findings support using PBI as the adjuvant radiotherapy modality for select patients with favorable-risk early-stage breast cancer.

Another meta-analysis looked at assessing the survival benefit of adding CDK4/6 inhibitors to standard ET in older patients with advanced breast cancer. The study included 10 trials with 1985 older patients with advanced ER+ breast cancer who received ET with or without CDK4/6 inhibitors. The findings showed that adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (HR 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients (age ≥ 65 years) with advanced breast cancer. Grade 3-4 neutropenia and diarrhea were similar in older patients. This study supports the use of CDK4/6 inhibitors as a reasonable treatment modality for older patients. More studies dedicated to the geriatric population are needed to help elaborate on the efficacy and tolerability of such agents in this population.

The phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 (NSABP B-42) trial evaluated the role of extended letrozole therapy in postmenopausal breast cancer patients who were disease-free after 5 years of aromatase inhibitor–based therapy. The study included 3966 postmenopausal women with stage I-IIIA HR+ breast cancer who were randomly assigned to receive letrozole or placebo for 5 more years. After a median follow-up of 10.3 years, letrozole significantly improved disease-free survival (10-year absolute benefit 3.4%; HR 0.85; P = .01) compared with placebo, although there were no differences noted in overall survival between the groups (HR 0.97, P = .74). Furthermore, letrozole significantly reduced the breast cancer–free interval (HR 0.75, ,P = .003) and distant recurrence (HR 0.72, P = .01). There were no notable differences in toxicity, particularly rates of osteoporotic fractures and arterial thrombotic events, between the groups. Extended therapy with aromatase inhibitors beyond 5 years can be considered for select patients with early-stage breast cancer. Careful consideration of risks and benefits is needed to make these recommendations. 

After a median follow-up of 21.6 mo, the dalpiciclib group demonstrated a significantly longer median progression-free survival (PFS) compared with the placebo group (30.6 mo vs 18.2 mo; stratified hazard ratio [HR] 0.51; 95% CI 0.38-0.69; P < .0001). Overall, the dalpiciclib group demonstrated a manageable safety profile, although a higher percentage of grade 3/4 adverse events was noted with dalpiciclib than with placebo (90% vs 12%), as expected. Overall survival data for this CDK4/6 inhibitor are yet to come. These results suggest that dalpiciclib in combination with endocrine therapy is an alternative treatment for this group of patients, especially in countries where the traditionally approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are not available.

The optimal sequencing of endocrine therapy (ET) after progression on CDK4/6 inhibitor–based therapy remains a challenge. In the phase 2 MAINTAIN trial, 119 patients (all of whom had HR+/HER2- metastatic breast cancer and who progressed on ET and CDK4/6 inhibitors) were randomly assigned to receive a different ET (fulvestrant or exemestane) from the previous ET they had received plus either the CDK4/6 inhibitor ribociclib or placebo. In the study by Kalinksky and colleagues, at a median follow-up of 18.2 mo, a significant improvement in PFS was observed in the switched ET-plus-ribociclib group compared with the switched ET-plus-placebo group (HR 0.57; P = .006). The phase 2 MAINTAIN trial is the first randomized trial to show the benefit of a CDK4/6 inhibitor after progression on another CDK4/6 inhibitor. It is important to note that the majority of patients in the MAINTAIN study previously received palbociclib in the first-line setting, which in recent studies has been demonstrated to be inferior to other CDK4/6 inhibitors. Therefore, it is important to confirm whether this will hold true upon progression from ribociclib or abemaciclib in the first-line setting. In addition, more data are needed to compare this approach with other ET treatment options, such as phosphoinositide 3-kinases inhibitors and oral selective estrogen receptor degraders.

There are several options for adjuvant radiation therapy for early-stage breast cancer. A meta-analysis of 14 randomized controlled trials and six comparative observational studies assessed the efficacy of whole breast irradiation (WBI) compared with partial breast irradiation (PBI) in 17,234 adults with early-stage breast cancer. Results of this meta-analysis showed that PBI was not significantly different from WBI, with similar rates of ipsilateral breast recurrence  at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91), although patients undergoing PBI reported fewer acute adverse events  compared with patients undergoing WBI (incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 adverse events (IRR 0.21; 95% CI 0.07-0.62). These findings support using PBI as the adjuvant radiotherapy modality for select patients with favorable-risk early-stage breast cancer.

Another meta-analysis looked at assessing the survival benefit of adding CDK4/6 inhibitors to standard ET in older patients with advanced breast cancer. The study included 10 trials with 1985 older patients with advanced ER+ breast cancer who received ET with or without CDK4/6 inhibitors. The findings showed that adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (HR 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients (age ≥ 65 years) with advanced breast cancer. Grade 3-4 neutropenia and diarrhea were similar in older patients. This study supports the use of CDK4/6 inhibitors as a reasonable treatment modality for older patients. More studies dedicated to the geriatric population are needed to help elaborate on the efficacy and tolerability of such agents in this population.

The phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 (NSABP B-42) trial evaluated the role of extended letrozole therapy in postmenopausal breast cancer patients who were disease-free after 5 years of aromatase inhibitor–based therapy. The study included 3966 postmenopausal women with stage I-IIIA HR+ breast cancer who were randomly assigned to receive letrozole or placebo for 5 more years. After a median follow-up of 10.3 years, letrozole significantly improved disease-free survival (10-year absolute benefit 3.4%; HR 0.85; P = .01) compared with placebo, although there were no differences noted in overall survival between the groups (HR 0.97, P = .74). Furthermore, letrozole significantly reduced the breast cancer–free interval (HR 0.75, ,P = .003) and distant recurrence (HR 0.72, P = .01). There were no notable differences in toxicity, particularly rates of osteoporotic fractures and arterial thrombotic events, between the groups. Extended therapy with aromatase inhibitors beyond 5 years can be considered for select patients with early-stage breast cancer. Careful consideration of risks and benefits is needed to make these recommendations. 

To the Editor:

Porocarcinoma is a rare malignancy of the eccrine sweat glands and is commonly misdiagnosed clinically. We present 2 cases of porocarcinoma and highlight key features of this uncommon disease.

A 65-year-old man presented to the emergency department with a chief concern of a bump on the head of 8 months' duration that gradually enlarged. The lesion recently became painful and contributed to frequent headaches. He reported a history of smoking 1 pack per day and denied trauma to the area or history of immunosuppression. He had no personal or family history of skin cancer. Physical examination revealed a 1.4-cm, heterochromic, pedunculated, keratotic tumor with crusting on the right temporal scalp (Figure 1). No lymphadenopathy was appreciated. The clinical differential diagnosis included irritated seborrheic keratosis, pyogenic granuloma, polypoid malignant melanoma, and nonmelanoma skin cancer. A biopsy of the lesion demonstrated a proliferation of cuboidal cells with focal ductular differentiation arranged in interanastamosing strands arising from the epidermis (Figure 2). Scattered mitotic figures, including atypical forms, cytologic atypia, and foci of necrosis, also were present. The findings were consistent with features of porocarcinoma. Contrast computed tomography of the neck showed no evidence of metastatic disease within the neck. A wide local excision was performed and yielded a tumor measuring 1.8×1.6×0.7 cm with a depth of 0.3 cm and uninvolved margins. No lymphovascular or perineural invasion was identified. At 4-month follow-up, the patient had a well-healed scar on the right scalp without evidence of recurrence or lymphadenopathy.

A 32-year-old woman presented to dermatology with a chief concern of a mass on the back of 2 years’ duration that rapidly enlarged and became painful following irritation from her bra strap 2 months earlier. She had no relevant medical history. Physical examination revealed a firm, tender, heterochromic nodule measuring 3.0×2.8 cm on the left mid back inferior to the left scapula (Figure 3). The lesion expressed serosanguineous discharge. No lymphadenopathy was appreciated on examination. The clinical differential diagnosis included an inflamed cyst, nodular melanoma, cutaneous metastasis, and nonmelanoma skin cancer. The patient underwent an excisional biopsy, which demonstrated porocarcinoma with positive margins, microsatellitosis, and evidence of lymphovascular invasion. Carcinoembryonic antigen immunohistochemistry highlighted ducts within the tumor (Figure 4). The patient underwent re-excision with 2-cm margins, and no residual tumor was appreciated on pathology.

Positron emission tomography and computed tomography revealed a hypermetabolic left axillary lymph node. Ultrasound-guided fine-needle aspiration was positive for malignant cells consistent with metastatic carcinoma. Dissection of left axillary lymph nodes yielded metastatic porocarcinoma in 2 of 13 nodes. The largest tumor deposit measured 0.9 cm, and no extracapsular extension was identified. The patient continues to be monitored with semiannual full-body skin examinations as well as positron emission tomography and computed tomography scans, with no evidence of recurrence 2 years later.

Porocarcinoma is a rare malignancy of the skin arising from the eccrine sweat glands¹ with an incidence rate of 0.4 cases per 1 million person-years in the United States. These tumors represent 0.005% to 0.01% of all skin cancers.² The mean age of onset is approximately 65 years with no predilection for sex. The mean time from initial presentation to treatment is 5.6 to 8.5 years.^3-5

Eccrine sweat glands consist of a straight intradermal duct (syrinx); coiled intradermal duct; and spiral intraepidermal duct (acrosyringium), which opens onto the skin. Both eccrine poromas (solitary benign eccrine gland tumors) and eccrine porocarcinomas develop from the acrosyringium. Eccrine poromas most commonly are found in sites containing the highest density of eccrine glands such as the palms, soles, axillae, and forehead, whereas porocarcinomas most commonly are found on the head, neck, arms, and legs.^1,3,4,6,7 A solitary painless nodule that may ulcerate or bleed is the most common presentation.^1,3-5,7

The etiology of eccrine porocarcinoma is poorly understood, but it has been found to arise de novo or to develop from pre-existing poromas or even from nevus sebaceus of Jadassohn. Chronic sunlight exposure, irradiation, lymphedema, trauma, and immunosuppression (eg, Hodgkin disease, chronic lymphocytic leukemia, HIV) have been reported as potential predisposing factors.^3,4,6,8,9

Eccrine porocarcinoma often is clinically misdiagnosed as nonmelanoma skin cancer, pyogenic granuloma, amelanotic melanoma, fibroma, verruca vulgaris, or metastatic carcinoma. Appropriate classification is essential, as metastasis is present in 25% to 31% of cases, and local recurrence occurs in 20% to 25% of cases.^1,3-5,7

Microscopically, porocarcinomas are comprised of atypical basaloid epithelial cells with focal ductular differentiation. Typically, there is an extensive intraepidermal component that invades into the dermis in anastomosing ribbons and cords. The degree of nuclear atypia, mitotic activity, and invasive growth pattern, as well as the presence of necrosis, are useful histologic features to differentiate porocarcinoma from poroma, which may be present in the background. Given the sometimes-extensive squamous differentiation, porocarcinoma can be confused with squamous cell carcinoma. In these cases, immunohistochemical stains such as epithelial membrane antigen or carcinoembryonic antigen can be used to highlight the ductal differentiation.^1,5,8,10

Poor histologic prognostic indicators include a high mitotic index (>14 mitoses per field), a tumor depth greater than 7 mm, and evidence of lymphovascular invasion. Positive lymph node involvement is associated with a 65% to 67% mortality rate.^1,8

Because of its propensity to metastasize via the lymphatic system and the high mortality rate associated with such metastases, early identification and treatment are essential. Treatment is accomplished via Mohs micrographic surgery or wide local excision with negative margins. Lymphadenectomy is indicated if regional lymph nodes are involved. Radiation and chemotherapy have been used in patients with metastatic and recurrent disease with mixed results.^1,3-5,7 There is no adequate standardized chemotherapy or drug regimen established for porocarcinoma.⁵ Tsunoda et al¹¹ proposed that sentinel lymph node biopsy should be considered first-line management of eccrine porocarcinoma; however, this remains unproven on the basis of a limited case series. Others conclude that sentinel lymph node biopsy should be recommended for cases with poor histologic prognostic features.^1,5

To the Editor:

Porocarcinoma is a rare malignancy of the eccrine sweat glands and is commonly misdiagnosed clinically. We present 2 cases of porocarcinoma and highlight key features of this uncommon disease.

A 65-year-old man presented to the emergency department with a chief concern of a bump on the head of 8 months' duration that gradually enlarged. The lesion recently became painful and contributed to frequent headaches. He reported a history of smoking 1 pack per day and denied trauma to the area or history of immunosuppression. He had no personal or family history of skin cancer. Physical examination revealed a 1.4-cm, heterochromic, pedunculated, keratotic tumor with crusting on the right temporal scalp (Figure 1). No lymphadenopathy was appreciated. The clinical differential diagnosis included irritated seborrheic keratosis, pyogenic granuloma, polypoid malignant melanoma, and nonmelanoma skin cancer. A biopsy of the lesion demonstrated a proliferation of cuboidal cells with focal ductular differentiation arranged in interanastamosing strands arising from the epidermis (Figure 2). Scattered mitotic figures, including atypical forms, cytologic atypia, and foci of necrosis, also were present. The findings were consistent with features of porocarcinoma. Contrast computed tomography of the neck showed no evidence of metastatic disease within the neck. A wide local excision was performed and yielded a tumor measuring 1.8×1.6×0.7 cm with a depth of 0.3 cm and uninvolved margins. No lymphovascular or perineural invasion was identified. At 4-month follow-up, the patient had a well-healed scar on the right scalp without evidence of recurrence or lymphadenopathy.

A 32-year-old woman presented to dermatology with a chief concern of a mass on the back of 2 years’ duration that rapidly enlarged and became painful following irritation from her bra strap 2 months earlier. She had no relevant medical history. Physical examination revealed a firm, tender, heterochromic nodule measuring 3.0×2.8 cm on the left mid back inferior to the left scapula (Figure 3). The lesion expressed serosanguineous discharge. No lymphadenopathy was appreciated on examination. The clinical differential diagnosis included an inflamed cyst, nodular melanoma, cutaneous metastasis, and nonmelanoma skin cancer. The patient underwent an excisional biopsy, which demonstrated porocarcinoma with positive margins, microsatellitosis, and evidence of lymphovascular invasion. Carcinoembryonic antigen immunohistochemistry highlighted ducts within the tumor (Figure 4). The patient underwent re-excision with 2-cm margins, and no residual tumor was appreciated on pathology.

Positron emission tomography and computed tomography revealed a hypermetabolic left axillary lymph node. Ultrasound-guided fine-needle aspiration was positive for malignant cells consistent with metastatic carcinoma. Dissection of left axillary lymph nodes yielded metastatic porocarcinoma in 2 of 13 nodes. The largest tumor deposit measured 0.9 cm, and no extracapsular extension was identified. The patient continues to be monitored with semiannual full-body skin examinations as well as positron emission tomography and computed tomography scans, with no evidence of recurrence 2 years later.

Porocarcinoma is a rare malignancy of the skin arising from the eccrine sweat glands¹ with an incidence rate of 0.4 cases per 1 million person-years in the United States. These tumors represent 0.005% to 0.01% of all skin cancers.² The mean age of onset is approximately 65 years with no predilection for sex. The mean time from initial presentation to treatment is 5.6 to 8.5 years.^3-5

Eccrine sweat glands consist of a straight intradermal duct (syrinx); coiled intradermal duct; and spiral intraepidermal duct (acrosyringium), which opens onto the skin. Both eccrine poromas (solitary benign eccrine gland tumors) and eccrine porocarcinomas develop from the acrosyringium. Eccrine poromas most commonly are found in sites containing the highest density of eccrine glands such as the palms, soles, axillae, and forehead, whereas porocarcinomas most commonly are found on the head, neck, arms, and legs.^1,3,4,6,7 A solitary painless nodule that may ulcerate or bleed is the most common presentation.^1,3-5,7

The etiology of eccrine porocarcinoma is poorly understood, but it has been found to arise de novo or to develop from pre-existing poromas or even from nevus sebaceus of Jadassohn. Chronic sunlight exposure, irradiation, lymphedema, trauma, and immunosuppression (eg, Hodgkin disease, chronic lymphocytic leukemia, HIV) have been reported as potential predisposing factors.^3,4,6,8,9

Eccrine porocarcinoma often is clinically misdiagnosed as nonmelanoma skin cancer, pyogenic granuloma, amelanotic melanoma, fibroma, verruca vulgaris, or metastatic carcinoma. Appropriate classification is essential, as metastasis is present in 25% to 31% of cases, and local recurrence occurs in 20% to 25% of cases.^1,3-5,7

Microscopically, porocarcinomas are comprised of atypical basaloid epithelial cells with focal ductular differentiation. Typically, there is an extensive intraepidermal component that invades into the dermis in anastomosing ribbons and cords. The degree of nuclear atypia, mitotic activity, and invasive growth pattern, as well as the presence of necrosis, are useful histologic features to differentiate porocarcinoma from poroma, which may be present in the background. Given the sometimes-extensive squamous differentiation, porocarcinoma can be confused with squamous cell carcinoma. In these cases, immunohistochemical stains such as epithelial membrane antigen or carcinoembryonic antigen can be used to highlight the ductal differentiation.^1,5,8,10

Poor histologic prognostic indicators include a high mitotic index (>14 mitoses per field), a tumor depth greater than 7 mm, and evidence of lymphovascular invasion. Positive lymph node involvement is associated with a 65% to 67% mortality rate.^1,8

Because of its propensity to metastasize via the lymphatic system and the high mortality rate associated with such metastases, early identification and treatment are essential. Treatment is accomplished via Mohs micrographic surgery or wide local excision with negative margins. Lymphadenectomy is indicated if regional lymph nodes are involved. Radiation and chemotherapy have been used in patients with metastatic and recurrent disease with mixed results.^1,3-5,7 There is no adequate standardized chemotherapy or drug regimen established for porocarcinoma.⁵ Tsunoda et al¹¹ proposed that sentinel lymph node biopsy should be considered first-line management of eccrine porocarcinoma; however, this remains unproven on the basis of a limited case series. Others conclude that sentinel lymph node biopsy should be recommended for cases with poor histologic prognostic features.^1,5

To the Editor:

Porocarcinoma is a rare malignancy of the eccrine sweat glands and is commonly misdiagnosed clinically. We present 2 cases of porocarcinoma and highlight key features of this uncommon disease.

A 65-year-old man presented to the emergency department with a chief concern of a bump on the head of 8 months' duration that gradually enlarged. The lesion recently became painful and contributed to frequent headaches. He reported a history of smoking 1 pack per day and denied trauma to the area or history of immunosuppression. He had no personal or family history of skin cancer. Physical examination revealed a 1.4-cm, heterochromic, pedunculated, keratotic tumor with crusting on the right temporal scalp (Figure 1). No lymphadenopathy was appreciated. The clinical differential diagnosis included irritated seborrheic keratosis, pyogenic granuloma, polypoid malignant melanoma, and nonmelanoma skin cancer. A biopsy of the lesion demonstrated a proliferation of cuboidal cells with focal ductular differentiation arranged in interanastamosing strands arising from the epidermis (Figure 2). Scattered mitotic figures, including atypical forms, cytologic atypia, and foci of necrosis, also were present. The findings were consistent with features of porocarcinoma. Contrast computed tomography of the neck showed no evidence of metastatic disease within the neck. A wide local excision was performed and yielded a tumor measuring 1.8×1.6×0.7 cm with a depth of 0.3 cm and uninvolved margins. No lymphovascular or perineural invasion was identified. At 4-month follow-up, the patient had a well-healed scar on the right scalp without evidence of recurrence or lymphadenopathy.

A 32-year-old woman presented to dermatology with a chief concern of a mass on the back of 2 years’ duration that rapidly enlarged and became painful following irritation from her bra strap 2 months earlier. She had no relevant medical history. Physical examination revealed a firm, tender, heterochromic nodule measuring 3.0×2.8 cm on the left mid back inferior to the left scapula (Figure 3). The lesion expressed serosanguineous discharge. No lymphadenopathy was appreciated on examination. The clinical differential diagnosis included an inflamed cyst, nodular melanoma, cutaneous metastasis, and nonmelanoma skin cancer. The patient underwent an excisional biopsy, which demonstrated porocarcinoma with positive margins, microsatellitosis, and evidence of lymphovascular invasion. Carcinoembryonic antigen immunohistochemistry highlighted ducts within the tumor (Figure 4). The patient underwent re-excision with 2-cm margins, and no residual tumor was appreciated on pathology.

Positron emission tomography and computed tomography revealed a hypermetabolic left axillary lymph node. Ultrasound-guided fine-needle aspiration was positive for malignant cells consistent with metastatic carcinoma. Dissection of left axillary lymph nodes yielded metastatic porocarcinoma in 2 of 13 nodes. The largest tumor deposit measured 0.9 cm, and no extracapsular extension was identified. The patient continues to be monitored with semiannual full-body skin examinations as well as positron emission tomography and computed tomography scans, with no evidence of recurrence 2 years later.

Porocarcinoma is a rare malignancy of the skin arising from the eccrine sweat glands¹ with an incidence rate of 0.4 cases per 1 million person-years in the United States. These tumors represent 0.005% to 0.01% of all skin cancers.² The mean age of onset is approximately 65 years with no predilection for sex. The mean time from initial presentation to treatment is 5.6 to 8.5 years.^3-5

Eccrine sweat glands consist of a straight intradermal duct (syrinx); coiled intradermal duct; and spiral intraepidermal duct (acrosyringium), which opens onto the skin. Both eccrine poromas (solitary benign eccrine gland tumors) and eccrine porocarcinomas develop from the acrosyringium. Eccrine poromas most commonly are found in sites containing the highest density of eccrine glands such as the palms, soles, axillae, and forehead, whereas porocarcinomas most commonly are found on the head, neck, arms, and legs.^1,3,4,6,7 A solitary painless nodule that may ulcerate or bleed is the most common presentation.^1,3-5,7

The etiology of eccrine porocarcinoma is poorly understood, but it has been found to arise de novo or to develop from pre-existing poromas or even from nevus sebaceus of Jadassohn. Chronic sunlight exposure, irradiation, lymphedema, trauma, and immunosuppression (eg, Hodgkin disease, chronic lymphocytic leukemia, HIV) have been reported as potential predisposing factors.^3,4,6,8,9

Eccrine porocarcinoma often is clinically misdiagnosed as nonmelanoma skin cancer, pyogenic granuloma, amelanotic melanoma, fibroma, verruca vulgaris, or metastatic carcinoma. Appropriate classification is essential, as metastasis is present in 25% to 31% of cases, and local recurrence occurs in 20% to 25% of cases.^1,3-5,7

Microscopically, porocarcinomas are comprised of atypical basaloid epithelial cells with focal ductular differentiation. Typically, there is an extensive intraepidermal component that invades into the dermis in anastomosing ribbons and cords. The degree of nuclear atypia, mitotic activity, and invasive growth pattern, as well as the presence of necrosis, are useful histologic features to differentiate porocarcinoma from poroma, which may be present in the background. Given the sometimes-extensive squamous differentiation, porocarcinoma can be confused with squamous cell carcinoma. In these cases, immunohistochemical stains such as epithelial membrane antigen or carcinoembryonic antigen can be used to highlight the ductal differentiation.^1,5,8,10

Poor histologic prognostic indicators include a high mitotic index (>14 mitoses per field), a tumor depth greater than 7 mm, and evidence of lymphovascular invasion. Positive lymph node involvement is associated with a 65% to 67% mortality rate.^1,8

Because of its propensity to metastasize via the lymphatic system and the high mortality rate associated with such metastases, early identification and treatment are essential. Treatment is accomplished via Mohs micrographic surgery or wide local excision with negative margins. Lymphadenectomy is indicated if regional lymph nodes are involved. Radiation and chemotherapy have been used in patients with metastatic and recurrent disease with mixed results.^1,3-5,7 There is no adequate standardized chemotherapy or drug regimen established for porocarcinoma.⁵ Tsunoda et al¹¹ proposed that sentinel lymph node biopsy should be considered first-line management of eccrine porocarcinoma; however, this remains unproven on the basis of a limited case series. Others conclude that sentinel lymph node biopsy should be recommended for cases with poor histologic prognostic features.^1,5

The US Preventive Services Task Force (USPSTF) recently issued draft recommendations on breast cancer screening that lower the starting age for routine mammography screening for those at average risk.¹ The proposed recommendations are an update to USPSTF’s 2016 guidance on this topic.

What’s different. There are 2 major differences in the new recommendations:

• Recommendation for routine mammography starting at age 40 for women at average risk for breast cancer (eg, no personal or family history or genetic risk factors). This is a “B” recommendation (offer or provide the service). Previously, the recommended age to start routine mammography was 50 years, with a “C” recommendation (individual decision-making) for those ages 40 to 49 years.
• No mention of digital tomosynthesis. Previously, this screening modality was rated as an “I” (insufficient evidence to assess). While the new draft recommendation does not mention tomosynthesis, the related evidence report concludes that there is still insufficient evidence to assess it.²

What’s the same. Several important recommendations have not changed. The USPSTF continues to state that the evidence is insufficient to assess the value of (1) supplemental screening with breast ultrasonography and magnetic resonance imaging in women with dense breasts and negative mammograms and (2) mammography in women ages 75 years and older.

And, most importantly, the USPSTF continues to recommend biennial, rather than annual, mammography screening. This recommendation is based on studies that show very little difference in outcomes between these strategies but higher rates of false-positive tests and subsequent biopsies with annual testing.²

What others say. USPSTF’s draft recommendations continue to differ from those of the American Cancer Society, which for average-risk women recommend individual decision-making from ages 40 to 45 years; routine annual mammography for those ages 45 to 54 years; annual or biennial mammography for those ages 55 years and older; and continued screening for women older than 75 years who are in good health and have a life expectancy ≥ 10 years.³

The USPSTF’s rationale for lowering the age at which to start routine mammography is a little puzzling. Several conclusions in the draft evidence report seem to contradict this recommendation:

In the summary of screening effectiveness, the report states “For women ages 39 to 49 years, the combined [relative risk] for breast cancer mortality was 0.92 (95% CI, 0.75 to 1.02; 9 trials); absolute breast cancer mortality reduction was 2.9 (95% CI, –0.6 to 8.9) deaths prevented per 10,000 women over 10 years. None of the trials indicated statistically significantly reduced breast cancer mortality with screening….”²

And in a summary of screening harms, it states that for “every case of invasive breast cancer detected by mammography screening in women age[s] 40 to 49 years, 464 women had screening mammography, 58 were recommended for additional diagnostic imaging, and 10 were recommended for biopsies.”²

The USPSTF apparently based its decision on a modeling study conducted by the Cancer Intervention and Surveillance Modeling Network (CISNET) at USPSTF’s request. This analysis found that screening biennially from ages 50 to 74 years resulted in about 7 breast cancer deaths averted over the lifetimes of 1000 females and that 1 additional death was averted if the starting age for screening was 40 years.⁴

Financial implications. The USPSTF’s change from a “C” to a “B” recommendation for women ages 40 to 49 years has financial implications. The Affordable Care Act mandates that all “A” and “B” recommendations by the USPSTF have to be provided by commercial health plans with no out-of-pocket costs. (This is currently being challenged in the courts.) However, any follow-up testing for abnormal results is not subject to this provision—so false-positive work-ups and biopsies may result in out-of-pocket costs.

What to discuss with your patients. For women ages 40 to 50 years, discuss the differences in mammography recommendations and the potential risks and benefits of the procedure, as well as financial implications; respect the patient’s decision.

For those ages 50 to 74 years, recommend biennial mammography.

For those older than 74 years, assess life expectancy and other health problems. Discuss the potential risks and benefits of the procedure and respect the patient’s decision.

For all patients, document all discussions and decisions.

The US Preventive Services Task Force (USPSTF) recently issued draft recommendations on breast cancer screening that lower the starting age for routine mammography screening for those at average risk.¹ The proposed recommendations are an update to USPSTF’s 2016 guidance on this topic.

What’s different. There are 2 major differences in the new recommendations:

• Recommendation for routine mammography starting at age 40 for women at average risk for breast cancer (eg, no personal or family history or genetic risk factors). This is a “B” recommendation (offer or provide the service). Previously, the recommended age to start routine mammography was 50 years, with a “C” recommendation (individual decision-making) for those ages 40 to 49 years.
• No mention of digital tomosynthesis. Previously, this screening modality was rated as an “I” (insufficient evidence to assess). While the new draft recommendation does not mention tomosynthesis, the related evidence report concludes that there is still insufficient evidence to assess it.²

What’s the same. Several important recommendations have not changed. The USPSTF continues to state that the evidence is insufficient to assess the value of (1) supplemental screening with breast ultrasonography and magnetic resonance imaging in women with dense breasts and negative mammograms and (2) mammography in women ages 75 years and older.

And, most importantly, the USPSTF continues to recommend biennial, rather than annual, mammography screening. This recommendation is based on studies that show very little difference in outcomes between these strategies but higher rates of false-positive tests and subsequent biopsies with annual testing.²

What others say. USPSTF’s draft recommendations continue to differ from those of the American Cancer Society, which for average-risk women recommend individual decision-making from ages 40 to 45 years; routine annual mammography for those ages 45 to 54 years; annual or biennial mammography for those ages 55 years and older; and continued screening for women older than 75 years who are in good health and have a life expectancy ≥ 10 years.³

The USPSTF’s rationale for lowering the age at which to start routine mammography is a little puzzling. Several conclusions in the draft evidence report seem to contradict this recommendation:

In the summary of screening effectiveness, the report states “For women ages 39 to 49 years, the combined [relative risk] for breast cancer mortality was 0.92 (95% CI, 0.75 to 1.02; 9 trials); absolute breast cancer mortality reduction was 2.9 (95% CI, –0.6 to 8.9) deaths prevented per 10,000 women over 10 years. None of the trials indicated statistically significantly reduced breast cancer mortality with screening….”²

And in a summary of screening harms, it states that for “every case of invasive breast cancer detected by mammography screening in women age[s] 40 to 49 years, 464 women had screening mammography, 58 were recommended for additional diagnostic imaging, and 10 were recommended for biopsies.”²

The USPSTF apparently based its decision on a modeling study conducted by the Cancer Intervention and Surveillance Modeling Network (CISNET) at USPSTF’s request. This analysis found that screening biennially from ages 50 to 74 years resulted in about 7 breast cancer deaths averted over the lifetimes of 1000 females and that 1 additional death was averted if the starting age for screening was 40 years.⁴

Financial implications. The USPSTF’s change from a “C” to a “B” recommendation for women ages 40 to 49 years has financial implications. The Affordable Care Act mandates that all “A” and “B” recommendations by the USPSTF have to be provided by commercial health plans with no out-of-pocket costs. (This is currently being challenged in the courts.) However, any follow-up testing for abnormal results is not subject to this provision—so false-positive work-ups and biopsies may result in out-of-pocket costs.

What to discuss with your patients. For women ages 40 to 50 years, discuss the differences in mammography recommendations and the potential risks and benefits of the procedure, as well as financial implications; respect the patient’s decision.

For those ages 50 to 74 years, recommend biennial mammography.

For those older than 74 years, assess life expectancy and other health problems. Discuss the potential risks and benefits of the procedure and respect the patient’s decision.

For all patients, document all discussions and decisions.

The US Preventive Services Task Force (USPSTF) recently issued draft recommendations on breast cancer screening that lower the starting age for routine mammography screening for those at average risk.¹ The proposed recommendations are an update to USPSTF’s 2016 guidance on this topic.

What’s different. There are 2 major differences in the new recommendations:

• Recommendation for routine mammography starting at age 40 for women at average risk for breast cancer (eg, no personal or family history or genetic risk factors). This is a “B” recommendation (offer or provide the service). Previously, the recommended age to start routine mammography was 50 years, with a “C” recommendation (individual decision-making) for those ages 40 to 49 years.
• No mention of digital tomosynthesis. Previously, this screening modality was rated as an “I” (insufficient evidence to assess). While the new draft recommendation does not mention tomosynthesis, the related evidence report concludes that there is still insufficient evidence to assess it.²

What’s the same. Several important recommendations have not changed. The USPSTF continues to state that the evidence is insufficient to assess the value of (1) supplemental screening with breast ultrasonography and magnetic resonance imaging in women with dense breasts and negative mammograms and (2) mammography in women ages 75 years and older.

And, most importantly, the USPSTF continues to recommend biennial, rather than annual, mammography screening. This recommendation is based on studies that show very little difference in outcomes between these strategies but higher rates of false-positive tests and subsequent biopsies with annual testing.²

What others say. USPSTF’s draft recommendations continue to differ from those of the American Cancer Society, which for average-risk women recommend individual decision-making from ages 40 to 45 years; routine annual mammography for those ages 45 to 54 years; annual or biennial mammography for those ages 55 years and older; and continued screening for women older than 75 years who are in good health and have a life expectancy ≥ 10 years.³

The USPSTF’s rationale for lowering the age at which to start routine mammography is a little puzzling. Several conclusions in the draft evidence report seem to contradict this recommendation:

In the summary of screening effectiveness, the report states “For women ages 39 to 49 years, the combined [relative risk] for breast cancer mortality was 0.92 (95% CI, 0.75 to 1.02; 9 trials); absolute breast cancer mortality reduction was 2.9 (95% CI, –0.6 to 8.9) deaths prevented per 10,000 women over 10 years. None of the trials indicated statistically significantly reduced breast cancer mortality with screening….”²

And in a summary of screening harms, it states that for “every case of invasive breast cancer detected by mammography screening in women age[s] 40 to 49 years, 464 women had screening mammography, 58 were recommended for additional diagnostic imaging, and 10 were recommended for biopsies.”²

The USPSTF apparently based its decision on a modeling study conducted by the Cancer Intervention and Surveillance Modeling Network (CISNET) at USPSTF’s request. This analysis found that screening biennially from ages 50 to 74 years resulted in about 7 breast cancer deaths averted over the lifetimes of 1000 females and that 1 additional death was averted if the starting age for screening was 40 years.⁴

Financial implications. The USPSTF’s change from a “C” to a “B” recommendation for women ages 40 to 49 years has financial implications. The Affordable Care Act mandates that all “A” and “B” recommendations by the USPSTF have to be provided by commercial health plans with no out-of-pocket costs. (This is currently being challenged in the courts.) However, any follow-up testing for abnormal results is not subject to this provision—so false-positive work-ups and biopsies may result in out-of-pocket costs.

What to discuss with your patients. For women ages 40 to 50 years, discuss the differences in mammography recommendations and the potential risks and benefits of the procedure, as well as financial implications; respect the patient’s decision.

For those ages 50 to 74 years, recommend biennial mammography.

For those older than 74 years, assess life expectancy and other health problems. Discuss the potential risks and benefits of the procedure and respect the patient’s decision.

For all patients, document all discussions and decisions.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, was first described in 1964. ¹ Since then, several subtypes of SS have been recognized, including classic or idiopathic, which typically follows an acute viral illness; cancer related, typically in the form of a paraneoplastic syndrome; and drug induced. ² Drug-induced SS is defined by the following: (1) an abrupt onset of painful erythematous plaques or nodules; (2) histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis; (3) pyrexia above 38 ° C; (4) temporal relationship between drug and clinical presentation or temporally related recurrence after rechallenge; and (5) temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids. ³ All 5 criteria must be met to make a diagnosis of drug-induced SS. Since these criteria were established by Walker and Cohen, ³ various drugs have been identified as causative agents, including antibiotics, antiepileptics, antiretrovirals, antineoplastic agents, antipsychotics, oral contraceptives, nonsteroidal anti-inflammatory agents, and retinoids. ⁴ W e present a rare case of SS caused by dupilumab, a monoclonal antibody therapy, used in the treatment of severe eosinophilic asthma and atopic dermatitis.

Case Report

A 53-year-old woman presented with painful skin lesions, arthralgia, fever, and leukocytosis following initiation of dupilumab. She had a history of adult-onset, severe, persistent eosinophilic asthma, as well as chronic rhinosinusitis with nasal polyps, plaque psoriasis, and hypertrophic cardiomyopathy. She started mepolizumab 3 years prior to the current presentation for persistently uncontrolled asthma with a baseline peripheral eosinophil count of 860 cells/µL. After 3 years of minimal response to mepolizumab, she was started on dupilumab. Within 2 weeks of the first dose of dupilumab, she started experiencing bilateral knee pain. She subsequently developed daily fevers (temperature, 38.3 °C to 39.4 °C), fatigue, and pain in the back of the neck and head. After the second dose of dupilumab, she started experiencing painful skin lesions on the bilateral knuckles, elbows, and abdomen (Figure 1). She had difficulty using her hands and walking secondary to intense arthralgia involving the bilateral finger joints, elbows, and knees. Her primary care physician obtained a laboratory evaluation, which revealed an elevated total white blood cell count of 20×10³/mm³ (reference range, 4–11×10³/mm³) with 27.5% neutrophils and severely elevated eosinophils above her baseline to 57.3% with an absolute eosinophil count of 11,700 cells/µL (reference range, <400 cells/µL). Further assessment revealed an elevated erythrocyte sedimentation rate of 64 mm/h (reference range, 0–30 mm/h) and C-reactive protein level of 34 mg/dL (reference range, ≤0.80 mg/dL), with negative antinuclear antibody, rheumatoid factor, antineutrophilic cytoplasmic antibody, and Lyme antibody. IgG, IgA, and IgM levels were within reference range, and the IgE level was not elevated above her baseline. She had normal serum tryptase, and a peripheral D816V c-KIT mutation was not detected. She was subsequently hospitalized for further evaluation, at which time there was no fever or localizing infectious signs or symptoms. An infectious evaluation including urinalysis; respiratory swab for adenovirus, coronaviruses, human metapneumovirus, rhinovirus/enterovirus, influenza A and B, parainfluenza viruses, respiratory syncytial virus, Chlamydophila pneumoniae, and Mycoplasma pneumoniae; Lyme serology; and a computed tomography (CT) scan of the chest, abdomen, and pelvis revealed no evidence of infection. A parasite evaluation was ordered but was not performed. There was no evidence of malignancy on CT of the chest, abdomen, and pelvis or CT of the head without contrast. A lumbar puncture was considered but was ultimately deferred.

At the current presentation, the patient was following up in the dermatology clinic shortly after discharge. The lesions on the fingers and arms were described by the dermatologist as deep, erythematous, 0.5-cm bullous papules. The differential diagnosis at this time included a cutaneous or systemic infection, vasculitis, drug eruption, or cutaneous manifestation of an autoimmune condition. A shave biopsy of a skin lesion on the right hand demonstrated epidermal necrosis with a dense dermal neutrophilic infiltrate consistent with a neutrophilic dermatosis (Figure 2). There was no evidence of leukocytoclastic vasculitis. The histologic differential diagnosis included cutaneous infection, neutrophilic dermatosis of the hand, and SS. Special stains for infectious organisms including Gram, Grocott methenamine-silver, and auramine-rhodamine stains were negative for bacterial, fungal, and mycobacterial organisms, ruling out cutaneous infection. A diagnosis of drug-induced SS was made based on the histologic findings, diffuse distribution of the lesions, negative infectious evaluation, lack of underlying malignancy or autoimmune conditions, and onset following initiation of dupilumab.

Dupilumab was discontinued, and the patient was started on prednisone with rapid improvement in the symptoms. She underwent a slow taper of the prednisone over approximately 2 months with a slow downtrend of eosinophils. She was transitioned to a different biologic agent, benralizumab, with no further recurrence of the rash or arthralgia.

Comment

Dupilumab is a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling by binding to the IL-4Rα subunit. By blocking IL-4Rα, dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE. Currently, dupilumab is approved to treat refractory forms of moderate to severe asthma characterized by an eosinophilic phenotype or with corticosteroid-dependent asthma, moderate to severe atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. The most common adverse events (incidence ≥1%) are injection-site reactions, oropharyngeal pain, and eosinophilia.⁵ Interestingly, our patient did exhibit a high degree of eosinophilia; however, she met all criteria for drug-induced SS, and the skin biopsy was not consistent with an eosinophilic process. Notably, the peripheral neutrophils were not elevated. Neutrophilia often is seen in classic SS but is not required for a diagnosis of drug-induced SS. Rare cases of dupilumab-associated arthritis and serum sickness–like reaction have been described,^6-8 but our patient’s presentation was distinct, given other described signs, symptoms, and skin biopsy results. Histopathology results were not consistent with leukocytoclastic vasculitis, a potential mimicker of SS. Although the infectious and paraneoplastic evaluation was not exhaustive, the negative imaging from head to pelvis, the lack of recurrence of skin lesions, and the laboratory abnormalities after dupilumab discontinuation supported the conclusion that the culprit was not an infection or underlying malignancy. She had not started any other medications during this time frame, leaving dupilumab as the most likely offending agent. The mechanism for this reaction is not clear. It is possible that inhibition of IL-4 and IL-13 in the T helper 2 (T_H2) cell pathway may have led to upregulated IL-17–mediated inflammation⁹ as well as a neutrophilic process in the skin, but this would not explain the concurrent peripheral eosinophilia that was noted. Further studies are needed to investigate the pathophysiology of SS.

Conclusion

We report a rare case of dupilumab-induced SS. Corticosteroids accompanied by cessation of the medication proved to be an effective treatment. Prescribers must be aware of SS as a potential adverse reaction, as prompt recognition and treatment are needed.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, was first described in 1964. ¹ Since then, several subtypes of SS have been recognized, including classic or idiopathic, which typically follows an acute viral illness; cancer related, typically in the form of a paraneoplastic syndrome; and drug induced. ² Drug-induced SS is defined by the following: (1) an abrupt onset of painful erythematous plaques or nodules; (2) histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis; (3) pyrexia above 38 ° C; (4) temporal relationship between drug and clinical presentation or temporally related recurrence after rechallenge; and (5) temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids. ³ All 5 criteria must be met to make a diagnosis of drug-induced SS. Since these criteria were established by Walker and Cohen, ³ various drugs have been identified as causative agents, including antibiotics, antiepileptics, antiretrovirals, antineoplastic agents, antipsychotics, oral contraceptives, nonsteroidal anti-inflammatory agents, and retinoids. ⁴ W e present a rare case of SS caused by dupilumab, a monoclonal antibody therapy, used in the treatment of severe eosinophilic asthma and atopic dermatitis.

Case Report

A 53-year-old woman presented with painful skin lesions, arthralgia, fever, and leukocytosis following initiation of dupilumab. She had a history of adult-onset, severe, persistent eosinophilic asthma, as well as chronic rhinosinusitis with nasal polyps, plaque psoriasis, and hypertrophic cardiomyopathy. She started mepolizumab 3 years prior to the current presentation for persistently uncontrolled asthma with a baseline peripheral eosinophil count of 860 cells/µL. After 3 years of minimal response to mepolizumab, she was started on dupilumab. Within 2 weeks of the first dose of dupilumab, she started experiencing bilateral knee pain. She subsequently developed daily fevers (temperature, 38.3 °C to 39.4 °C), fatigue, and pain in the back of the neck and head. After the second dose of dupilumab, she started experiencing painful skin lesions on the bilateral knuckles, elbows, and abdomen (Figure 1). She had difficulty using her hands and walking secondary to intense arthralgia involving the bilateral finger joints, elbows, and knees. Her primary care physician obtained a laboratory evaluation, which revealed an elevated total white blood cell count of 20×10³/mm³ (reference range, 4–11×10³/mm³) with 27.5% neutrophils and severely elevated eosinophils above her baseline to 57.3% with an absolute eosinophil count of 11,700 cells/µL (reference range, <400 cells/µL). Further assessment revealed an elevated erythrocyte sedimentation rate of 64 mm/h (reference range, 0–30 mm/h) and C-reactive protein level of 34 mg/dL (reference range, ≤0.80 mg/dL), with negative antinuclear antibody, rheumatoid factor, antineutrophilic cytoplasmic antibody, and Lyme antibody. IgG, IgA, and IgM levels were within reference range, and the IgE level was not elevated above her baseline. She had normal serum tryptase, and a peripheral D816V c-KIT mutation was not detected. She was subsequently hospitalized for further evaluation, at which time there was no fever or localizing infectious signs or symptoms. An infectious evaluation including urinalysis; respiratory swab for adenovirus, coronaviruses, human metapneumovirus, rhinovirus/enterovirus, influenza A and B, parainfluenza viruses, respiratory syncytial virus, Chlamydophila pneumoniae, and Mycoplasma pneumoniae; Lyme serology; and a computed tomography (CT) scan of the chest, abdomen, and pelvis revealed no evidence of infection. A parasite evaluation was ordered but was not performed. There was no evidence of malignancy on CT of the chest, abdomen, and pelvis or CT of the head without contrast. A lumbar puncture was considered but was ultimately deferred.

At the current presentation, the patient was following up in the dermatology clinic shortly after discharge. The lesions on the fingers and arms were described by the dermatologist as deep, erythematous, 0.5-cm bullous papules. The differential diagnosis at this time included a cutaneous or systemic infection, vasculitis, drug eruption, or cutaneous manifestation of an autoimmune condition. A shave biopsy of a skin lesion on the right hand demonstrated epidermal necrosis with a dense dermal neutrophilic infiltrate consistent with a neutrophilic dermatosis (Figure 2). There was no evidence of leukocytoclastic vasculitis. The histologic differential diagnosis included cutaneous infection, neutrophilic dermatosis of the hand, and SS. Special stains for infectious organisms including Gram, Grocott methenamine-silver, and auramine-rhodamine stains were negative for bacterial, fungal, and mycobacterial organisms, ruling out cutaneous infection. A diagnosis of drug-induced SS was made based on the histologic findings, diffuse distribution of the lesions, negative infectious evaluation, lack of underlying malignancy or autoimmune conditions, and onset following initiation of dupilumab.

Dupilumab was discontinued, and the patient was started on prednisone with rapid improvement in the symptoms. She underwent a slow taper of the prednisone over approximately 2 months with a slow downtrend of eosinophils. She was transitioned to a different biologic agent, benralizumab, with no further recurrence of the rash or arthralgia.

Comment

Dupilumab is a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling by binding to the IL-4Rα subunit. By blocking IL-4Rα, dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE. Currently, dupilumab is approved to treat refractory forms of moderate to severe asthma characterized by an eosinophilic phenotype or with corticosteroid-dependent asthma, moderate to severe atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. The most common adverse events (incidence ≥1%) are injection-site reactions, oropharyngeal pain, and eosinophilia.⁵ Interestingly, our patient did exhibit a high degree of eosinophilia; however, she met all criteria for drug-induced SS, and the skin biopsy was not consistent with an eosinophilic process. Notably, the peripheral neutrophils were not elevated. Neutrophilia often is seen in classic SS but is not required for a diagnosis of drug-induced SS. Rare cases of dupilumab-associated arthritis and serum sickness–like reaction have been described,^6-8 but our patient’s presentation was distinct, given other described signs, symptoms, and skin biopsy results. Histopathology results were not consistent with leukocytoclastic vasculitis, a potential mimicker of SS. Although the infectious and paraneoplastic evaluation was not exhaustive, the negative imaging from head to pelvis, the lack of recurrence of skin lesions, and the laboratory abnormalities after dupilumab discontinuation supported the conclusion that the culprit was not an infection or underlying malignancy. She had not started any other medications during this time frame, leaving dupilumab as the most likely offending agent. The mechanism for this reaction is not clear. It is possible that inhibition of IL-4 and IL-13 in the T helper 2 (T_H2) cell pathway may have led to upregulated IL-17–mediated inflammation⁹ as well as a neutrophilic process in the skin, but this would not explain the concurrent peripheral eosinophilia that was noted. Further studies are needed to investigate the pathophysiology of SS.

Conclusion

We report a rare case of dupilumab-induced SS. Corticosteroids accompanied by cessation of the medication proved to be an effective treatment. Prescribers must be aware of SS as a potential adverse reaction, as prompt recognition and treatment are needed.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, was first described in 1964. ¹ Since then, several subtypes of SS have been recognized, including classic or idiopathic, which typically follows an acute viral illness; cancer related, typically in the form of a paraneoplastic syndrome; and drug induced. ² Drug-induced SS is defined by the following: (1) an abrupt onset of painful erythematous plaques or nodules; (2) histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis; (3) pyrexia above 38 ° C; (4) temporal relationship between drug and clinical presentation or temporally related recurrence after rechallenge; and (5) temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids. ³ All 5 criteria must be met to make a diagnosis of drug-induced SS. Since these criteria were established by Walker and Cohen, ³ various drugs have been identified as causative agents, including antibiotics, antiepileptics, antiretrovirals, antineoplastic agents, antipsychotics, oral contraceptives, nonsteroidal anti-inflammatory agents, and retinoids. ⁴ W e present a rare case of SS caused by dupilumab, a monoclonal antibody therapy, used in the treatment of severe eosinophilic asthma and atopic dermatitis.

Case Report

A 53-year-old woman presented with painful skin lesions, arthralgia, fever, and leukocytosis following initiation of dupilumab. She had a history of adult-onset, severe, persistent eosinophilic asthma, as well as chronic rhinosinusitis with nasal polyps, plaque psoriasis, and hypertrophic cardiomyopathy. She started mepolizumab 3 years prior to the current presentation for persistently uncontrolled asthma with a baseline peripheral eosinophil count of 860 cells/µL. After 3 years of minimal response to mepolizumab, she was started on dupilumab. Within 2 weeks of the first dose of dupilumab, she started experiencing bilateral knee pain. She subsequently developed daily fevers (temperature, 38.3 °C to 39.4 °C), fatigue, and pain in the back of the neck and head. After the second dose of dupilumab, she started experiencing painful skin lesions on the bilateral knuckles, elbows, and abdomen (Figure 1). She had difficulty using her hands and walking secondary to intense arthralgia involving the bilateral finger joints, elbows, and knees. Her primary care physician obtained a laboratory evaluation, which revealed an elevated total white blood cell count of 20×10³/mm³ (reference range, 4–11×10³/mm³) with 27.5% neutrophils and severely elevated eosinophils above her baseline to 57.3% with an absolute eosinophil count of 11,700 cells/µL (reference range, <400 cells/µL). Further assessment revealed an elevated erythrocyte sedimentation rate of 64 mm/h (reference range, 0–30 mm/h) and C-reactive protein level of 34 mg/dL (reference range, ≤0.80 mg/dL), with negative antinuclear antibody, rheumatoid factor, antineutrophilic cytoplasmic antibody, and Lyme antibody. IgG, IgA, and IgM levels were within reference range, and the IgE level was not elevated above her baseline. She had normal serum tryptase, and a peripheral D816V c-KIT mutation was not detected. She was subsequently hospitalized for further evaluation, at which time there was no fever or localizing infectious signs or symptoms. An infectious evaluation including urinalysis; respiratory swab for adenovirus, coronaviruses, human metapneumovirus, rhinovirus/enterovirus, influenza A and B, parainfluenza viruses, respiratory syncytial virus, Chlamydophila pneumoniae, and Mycoplasma pneumoniae; Lyme serology; and a computed tomography (CT) scan of the chest, abdomen, and pelvis revealed no evidence of infection. A parasite evaluation was ordered but was not performed. There was no evidence of malignancy on CT of the chest, abdomen, and pelvis or CT of the head without contrast. A lumbar puncture was considered but was ultimately deferred.

At the current presentation, the patient was following up in the dermatology clinic shortly after discharge. The lesions on the fingers and arms were described by the dermatologist as deep, erythematous, 0.5-cm bullous papules. The differential diagnosis at this time included a cutaneous or systemic infection, vasculitis, drug eruption, or cutaneous manifestation of an autoimmune condition. A shave biopsy of a skin lesion on the right hand demonstrated epidermal necrosis with a dense dermal neutrophilic infiltrate consistent with a neutrophilic dermatosis (Figure 2). There was no evidence of leukocytoclastic vasculitis. The histologic differential diagnosis included cutaneous infection, neutrophilic dermatosis of the hand, and SS. Special stains for infectious organisms including Gram, Grocott methenamine-silver, and auramine-rhodamine stains were negative for bacterial, fungal, and mycobacterial organisms, ruling out cutaneous infection. A diagnosis of drug-induced SS was made based on the histologic findings, diffuse distribution of the lesions, negative infectious evaluation, lack of underlying malignancy or autoimmune conditions, and onset following initiation of dupilumab.

Dupilumab was discontinued, and the patient was started on prednisone with rapid improvement in the symptoms. She underwent a slow taper of the prednisone over approximately 2 months with a slow downtrend of eosinophils. She was transitioned to a different biologic agent, benralizumab, with no further recurrence of the rash or arthralgia.

Comment

Dupilumab is a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling by binding to the IL-4Rα subunit. By blocking IL-4Rα, dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE. Currently, dupilumab is approved to treat refractory forms of moderate to severe asthma characterized by an eosinophilic phenotype or with corticosteroid-dependent asthma, moderate to severe atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. The most common adverse events (incidence ≥1%) are injection-site reactions, oropharyngeal pain, and eosinophilia.⁵ Interestingly, our patient did exhibit a high degree of eosinophilia; however, she met all criteria for drug-induced SS, and the skin biopsy was not consistent with an eosinophilic process. Notably, the peripheral neutrophils were not elevated. Neutrophilia often is seen in classic SS but is not required for a diagnosis of drug-induced SS. Rare cases of dupilumab-associated arthritis and serum sickness–like reaction have been described,^6-8 but our patient’s presentation was distinct, given other described signs, symptoms, and skin biopsy results. Histopathology results were not consistent with leukocytoclastic vasculitis, a potential mimicker of SS. Although the infectious and paraneoplastic evaluation was not exhaustive, the negative imaging from head to pelvis, the lack of recurrence of skin lesions, and the laboratory abnormalities after dupilumab discontinuation supported the conclusion that the culprit was not an infection or underlying malignancy. She had not started any other medications during this time frame, leaving dupilumab as the most likely offending agent. The mechanism for this reaction is not clear. It is possible that inhibition of IL-4 and IL-13 in the T helper 2 (T_H2) cell pathway may have led to upregulated IL-17–mediated inflammation⁹ as well as a neutrophilic process in the skin, but this would not explain the concurrent peripheral eosinophilia that was noted. Further studies are needed to investigate the pathophysiology of SS.

Conclusion

We report a rare case of dupilumab-induced SS. Corticosteroids accompanied by cessation of the medication proved to be an effective treatment. Prescribers must be aware of SS as a potential adverse reaction, as prompt recognition and treatment are needed.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

To the Editor:

A 58-year-old woman presented to our dermatology clinic with a pruritic weeping eruption circumferentially on the distal digits of both hands of 5 weeks’ duration. The patient disclosed that she had been receiving dip powder manicures at a local nail salon approximately every 2 weeks over the last 3 to 6 months. She had received frequent acrylic nail extensions over the last 8 years prior to starting the dip powder manicures. Physical examination revealed well-demarcated eczematous plaques involving the lateral and proximal nail folds of the right thumb with an overlying serous crust and loss of the cuticle (Figure 1A). Erythematous plaques with firm deep-seated microvesicles also were present on the other digits, distributed distal to the distal interphalangeal joints (Figure 1B). She was diagnosed with dyshidroticlike contact dermatitis and paronychia. Treatment included phenol 1.5% colorless solution and clobetasol ointment 0.05% for twice-daily application to the affected areas. The patient also was advised to stop receiving manicures. At 1-month follow-up, the paronychia had resolved and the dermatitis had nearly resolved.

Dip powder manicures use a wet adhesive base coat with acrylic powder and an activator topcoat to initiate a chemical reaction that hardens and sets the nail polish. The colored powder typically is applied by dipping the digit up to the distal interphalangeal joint into a small container of loose powder and then brushing away the excess (Figure 2). Acrylate, a chemical present in dip powders, is a known allergen and has been associated with the development of allergic contact dermatitis and onychodystrophy in patients after receiving acrylic and UV-cured gel polish manicures.^1,2 Inadequate sanitation practices at nail salons also have been associated with infection transmission.^3,4 Additionally, the news media has covered the potential risk of infection due to contamination from reused dip manicure powder and the use of communal powder containers.⁵

To increase clinical awareness of the dip manicure technique, we describe the presentation and successful treatment of dyshidroticlike contact dermatitis and paronychia that occurred in a patient after she received a dip powder manicure. Dermatoses and infection limited to the distal phalanges will present in patients more frequently as dip powder manicures continue to increase in popularity and frequency.

To the Editor:

A 58-year-old woman presented to our dermatology clinic with a pruritic weeping eruption circumferentially on the distal digits of both hands of 5 weeks’ duration. The patient disclosed that she had been receiving dip powder manicures at a local nail salon approximately every 2 weeks over the last 3 to 6 months. She had received frequent acrylic nail extensions over the last 8 years prior to starting the dip powder manicures. Physical examination revealed well-demarcated eczematous plaques involving the lateral and proximal nail folds of the right thumb with an overlying serous crust and loss of the cuticle (Figure 1A). Erythematous plaques with firm deep-seated microvesicles also were present on the other digits, distributed distal to the distal interphalangeal joints (Figure 1B). She was diagnosed with dyshidroticlike contact dermatitis and paronychia. Treatment included phenol 1.5% colorless solution and clobetasol ointment 0.05% for twice-daily application to the affected areas. The patient also was advised to stop receiving manicures. At 1-month follow-up, the paronychia had resolved and the dermatitis had nearly resolved.

Dip powder manicures use a wet adhesive base coat with acrylic powder and an activator topcoat to initiate a chemical reaction that hardens and sets the nail polish. The colored powder typically is applied by dipping the digit up to the distal interphalangeal joint into a small container of loose powder and then brushing away the excess (Figure 2). Acrylate, a chemical present in dip powders, is a known allergen and has been associated with the development of allergic contact dermatitis and onychodystrophy in patients after receiving acrylic and UV-cured gel polish manicures.^1,2 Inadequate sanitation practices at nail salons also have been associated with infection transmission.^3,4 Additionally, the news media has covered the potential risk of infection due to contamination from reused dip manicure powder and the use of communal powder containers.⁵

To increase clinical awareness of the dip manicure technique, we describe the presentation and successful treatment of dyshidroticlike contact dermatitis and paronychia that occurred in a patient after she received a dip powder manicure. Dermatoses and infection limited to the distal phalanges will present in patients more frequently as dip powder manicures continue to increase in popularity and frequency.

To the Editor:

A 58-year-old woman presented to our dermatology clinic with a pruritic weeping eruption circumferentially on the distal digits of both hands of 5 weeks’ duration. The patient disclosed that she had been receiving dip powder manicures at a local nail salon approximately every 2 weeks over the last 3 to 6 months. She had received frequent acrylic nail extensions over the last 8 years prior to starting the dip powder manicures. Physical examination revealed well-demarcated eczematous plaques involving the lateral and proximal nail folds of the right thumb with an overlying serous crust and loss of the cuticle (Figure 1A). Erythematous plaques with firm deep-seated microvesicles also were present on the other digits, distributed distal to the distal interphalangeal joints (Figure 1B). She was diagnosed with dyshidroticlike contact dermatitis and paronychia. Treatment included phenol 1.5% colorless solution and clobetasol ointment 0.05% for twice-daily application to the affected areas. The patient also was advised to stop receiving manicures. At 1-month follow-up, the paronychia had resolved and the dermatitis had nearly resolved.

Dip powder manicures use a wet adhesive base coat with acrylic powder and an activator topcoat to initiate a chemical reaction that hardens and sets the nail polish. The colored powder typically is applied by dipping the digit up to the distal interphalangeal joint into a small container of loose powder and then brushing away the excess (Figure 2). Acrylate, a chemical present in dip powders, is a known allergen and has been associated with the development of allergic contact dermatitis and onychodystrophy in patients after receiving acrylic and UV-cured gel polish manicures.^1,2 Inadequate sanitation practices at nail salons also have been associated with infection transmission.^3,4 Additionally, the news media has covered the potential risk of infection due to contamination from reused dip manicure powder and the use of communal powder containers.⁵

To increase clinical awareness of the dip manicure technique, we describe the presentation and successful treatment of dyshidroticlike contact dermatitis and paronychia that occurred in a patient after she received a dip powder manicure. Dermatoses and infection limited to the distal phalanges will present in patients more frequently as dip powder manicures continue to increase in popularity and frequency.