Case Letter

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

To the Editor:

The evolution in the understanding of psoriasis and psoriatic arthritis has unfolded many new facets of this immune-mediated inflammatory disease. Once considered to be just a cutaneous disease, psoriasis is not actually confined to skin but can involve almost any other system of the body. Cardiovascular morbidity and mortality are the major concerns in patients with psoriasis. We report the sudden death of a young man with severe psoriasis.

A 31-year-old man was admitted for severe psoriasis with pustular exacerbation (Figures 1A and 1B). He had moderate to severe unstable disease during the last 8 years and was managed with oral methotrexate (0.3–0.5 mg/kg/wk). He was not compliant with treatment, which led to multiple relapses. There was no personal or family history of risk factors for cardiovascular events (CVEs). At the time of present hospitalization, his vital parameters were normal. Physical examination revealed erythematous scaly plaques on more than 75% of the body surface area. Multiple pustules also were noted, often coalescing to form plaques (Figure 1C). Baseline investigations consisting of complete blood cell count, lipid profile, liver and renal functions, and chest radiography were within reference range. Baseline electrocardiogram (ECG) at admission was unremarkable (Figure 2A), except for sinus tachycardia. Low-voltage complexes in limb leads were appreciated as well as a corrected QT interval of 420 milliseconds (within reference range). Echocardiography was normal (visual ejection fraction of 60%).

The patient was unable to tolerate methotrexate due to excessive nausea; he was started on oral acitretin 25 mg once daily. There was no improvement in psoriasis over the following week, and he reported mild upper abdominal discomfort. He did not have any chest pain or dyspnea, and his pulse and blood pressure were normal. Serum electrolytes, liver function, lipid profile, and an ultrasound of the abdomen revealed no abnormalities. A repeat ECG showed no changes, and cardiac biomarkers were not elevated. Two days later, the patient collapsed while still in the hospital. A cardiac monitor and ECG showed ventricular tachycardia (VT)(Figure 2B); however, serum electrolytes, calcium, magnesium, and phosphorus levels were within reference range. Aggressive resuscitative measures including multiple attempts at cardioversion with up to 200 J (biphasic) and intravenous amiodarone infusion failed to revive the patient, and he died.

Proinflammatory cytokines such as IL-6 and tumor necrosis factor α are increased in young people with ventricular arrhythmias who have no evidence of myocardial injury (MI), suggesting an inflammatory background is involved.¹ Psoriasis, a common immune-mediated inflammatory disease, has a chronic state of systemic inflammation with notably higher serum levels of tumor necrosis factor α, IFN-γ, IL-6, IL-8, IL-12, and IL-18 compared to controls.² This inflammation is not confined to skin but can involve blood vessels, joints, and the liver, as demonstrated by increased fluorodeoxyglucose uptake.³ It also seems to exert its influence on supraventricular beat development in patients with psoriasis who do not have a history of CVEs.⁴ Tumor necrosis factor α is one of the major cytokines playing a role in the inflammatory process of psoriasis. Studies have shown serum levels of tumor necrosis factor α to correlate with the clinical symptoms of heart failure and to supraventricular arrhythmia in animal models.⁴ Various extreme CVEs can be an expression of this ongoing dynamic process. It would be interesting to know which specific factors among these inflammatory cytokines lead to rhythm irregularities.

Another theory is that young patients may experience micro-MI during the disease course. These small infarcted areas may act as aberrant pulse generators or lead to conduction disturbances. One study found increased correct QT interval dispersion, a predictor of ventricular arrhythmias, to be associated with psoriasis.⁵ A nationwide population-based matched cohort study by Chiu et al⁶ revealed that patients with psoriasis have a higher risk for arrhythmia independent of traditional cardiovascular risk factors. Our patient also had severe unstable psoriasis for 8 years that may have led to increased accumulation of proarrhythmogenic cytokines in the heart and could have led to VT.

Acitretin as a potential cause of sudden cardiac death remains a possibility in our case; however, the exact mechanism leading to such sudden arrhythmia is lacking. Acitretin is known to increase serum triglycerides and cholesterol, specifically by shifting high-density lipoproteins to low-density lipoproteins, thereby increasing the risk for CVE. However, it takes time for such derangement to occur, eventually leading to CVE. Mittal et al⁷ reported a psoriasis patient who died secondary to MI after 5 days of low-dose acitretin. Lack of evidence makes acitretin a less likely cause of mortality.

We present a case of sudden cardiac death secondary to VT in a young patient with psoriasis and no other traditional cardiovascular risk factors. This case highlights the importance of being vigilant for adverse CVEs such as arrhythmia in psoriatic patients, especially in younger patients with severe unstable disease.

To the Editor:

The evolution in the understanding of psoriasis and psoriatic arthritis has unfolded many new facets of this immune-mediated inflammatory disease. Once considered to be just a cutaneous disease, psoriasis is not actually confined to skin but can involve almost any other system of the body. Cardiovascular morbidity and mortality are the major concerns in patients with psoriasis. We report the sudden death of a young man with severe psoriasis.

A 31-year-old man was admitted for severe psoriasis with pustular exacerbation (Figures 1A and 1B). He had moderate to severe unstable disease during the last 8 years and was managed with oral methotrexate (0.3–0.5 mg/kg/wk). He was not compliant with treatment, which led to multiple relapses. There was no personal or family history of risk factors for cardiovascular events (CVEs). At the time of present hospitalization, his vital parameters were normal. Physical examination revealed erythematous scaly plaques on more than 75% of the body surface area. Multiple pustules also were noted, often coalescing to form plaques (Figure 1C). Baseline investigations consisting of complete blood cell count, lipid profile, liver and renal functions, and chest radiography were within reference range. Baseline electrocardiogram (ECG) at admission was unremarkable (Figure 2A), except for sinus tachycardia. Low-voltage complexes in limb leads were appreciated as well as a corrected QT interval of 420 milliseconds (within reference range). Echocardiography was normal (visual ejection fraction of 60%).

The patient was unable to tolerate methotrexate due to excessive nausea; he was started on oral acitretin 25 mg once daily. There was no improvement in psoriasis over the following week, and he reported mild upper abdominal discomfort. He did not have any chest pain or dyspnea, and his pulse and blood pressure were normal. Serum electrolytes, liver function, lipid profile, and an ultrasound of the abdomen revealed no abnormalities. A repeat ECG showed no changes, and cardiac biomarkers were not elevated. Two days later, the patient collapsed while still in the hospital. A cardiac monitor and ECG showed ventricular tachycardia (VT)(Figure 2B); however, serum electrolytes, calcium, magnesium, and phosphorus levels were within reference range. Aggressive resuscitative measures including multiple attempts at cardioversion with up to 200 J (biphasic) and intravenous amiodarone infusion failed to revive the patient, and he died.

Proinflammatory cytokines such as IL-6 and tumor necrosis factor α are increased in young people with ventricular arrhythmias who have no evidence of myocardial injury (MI), suggesting an inflammatory background is involved.¹ Psoriasis, a common immune-mediated inflammatory disease, has a chronic state of systemic inflammation with notably higher serum levels of tumor necrosis factor α, IFN-γ, IL-6, IL-8, IL-12, and IL-18 compared to controls.² This inflammation is not confined to skin but can involve blood vessels, joints, and the liver, as demonstrated by increased fluorodeoxyglucose uptake.³ It also seems to exert its influence on supraventricular beat development in patients with psoriasis who do not have a history of CVEs.⁴ Tumor necrosis factor α is one of the major cytokines playing a role in the inflammatory process of psoriasis. Studies have shown serum levels of tumor necrosis factor α to correlate with the clinical symptoms of heart failure and to supraventricular arrhythmia in animal models.⁴ Various extreme CVEs can be an expression of this ongoing dynamic process. It would be interesting to know which specific factors among these inflammatory cytokines lead to rhythm irregularities.

Another theory is that young patients may experience micro-MI during the disease course. These small infarcted areas may act as aberrant pulse generators or lead to conduction disturbances. One study found increased correct QT interval dispersion, a predictor of ventricular arrhythmias, to be associated with psoriasis.⁵ A nationwide population-based matched cohort study by Chiu et al⁶ revealed that patients with psoriasis have a higher risk for arrhythmia independent of traditional cardiovascular risk factors. Our patient also had severe unstable psoriasis for 8 years that may have led to increased accumulation of proarrhythmogenic cytokines in the heart and could have led to VT.

Acitretin as a potential cause of sudden cardiac death remains a possibility in our case; however, the exact mechanism leading to such sudden arrhythmia is lacking. Acitretin is known to increase serum triglycerides and cholesterol, specifically by shifting high-density lipoproteins to low-density lipoproteins, thereby increasing the risk for CVE. However, it takes time for such derangement to occur, eventually leading to CVE. Mittal et al⁷ reported a psoriasis patient who died secondary to MI after 5 days of low-dose acitretin. Lack of evidence makes acitretin a less likely cause of mortality.

We present a case of sudden cardiac death secondary to VT in a young patient with psoriasis and no other traditional cardiovascular risk factors. This case highlights the importance of being vigilant for adverse CVEs such as arrhythmia in psoriatic patients, especially in younger patients with severe unstable disease.

To the Editor:

The evolution in the understanding of psoriasis and psoriatic arthritis has unfolded many new facets of this immune-mediated inflammatory disease. Once considered to be just a cutaneous disease, psoriasis is not actually confined to skin but can involve almost any other system of the body. Cardiovascular morbidity and mortality are the major concerns in patients with psoriasis. We report the sudden death of a young man with severe psoriasis.

A 31-year-old man was admitted for severe psoriasis with pustular exacerbation (Figures 1A and 1B). He had moderate to severe unstable disease during the last 8 years and was managed with oral methotrexate (0.3–0.5 mg/kg/wk). He was not compliant with treatment, which led to multiple relapses. There was no personal or family history of risk factors for cardiovascular events (CVEs). At the time of present hospitalization, his vital parameters were normal. Physical examination revealed erythematous scaly plaques on more than 75% of the body surface area. Multiple pustules also were noted, often coalescing to form plaques (Figure 1C). Baseline investigations consisting of complete blood cell count, lipid profile, liver and renal functions, and chest radiography were within reference range. Baseline electrocardiogram (ECG) at admission was unremarkable (Figure 2A), except for sinus tachycardia. Low-voltage complexes in limb leads were appreciated as well as a corrected QT interval of 420 milliseconds (within reference range). Echocardiography was normal (visual ejection fraction of 60%).

The patient was unable to tolerate methotrexate due to excessive nausea; he was started on oral acitretin 25 mg once daily. There was no improvement in psoriasis over the following week, and he reported mild upper abdominal discomfort. He did not have any chest pain or dyspnea, and his pulse and blood pressure were normal. Serum electrolytes, liver function, lipid profile, and an ultrasound of the abdomen revealed no abnormalities. A repeat ECG showed no changes, and cardiac biomarkers were not elevated. Two days later, the patient collapsed while still in the hospital. A cardiac monitor and ECG showed ventricular tachycardia (VT)(Figure 2B); however, serum electrolytes, calcium, magnesium, and phosphorus levels were within reference range. Aggressive resuscitative measures including multiple attempts at cardioversion with up to 200 J (biphasic) and intravenous amiodarone infusion failed to revive the patient, and he died.

Proinflammatory cytokines such as IL-6 and tumor necrosis factor α are increased in young people with ventricular arrhythmias who have no evidence of myocardial injury (MI), suggesting an inflammatory background is involved.¹ Psoriasis, a common immune-mediated inflammatory disease, has a chronic state of systemic inflammation with notably higher serum levels of tumor necrosis factor α, IFN-γ, IL-6, IL-8, IL-12, and IL-18 compared to controls.² This inflammation is not confined to skin but can involve blood vessels, joints, and the liver, as demonstrated by increased fluorodeoxyglucose uptake.³ It also seems to exert its influence on supraventricular beat development in patients with psoriasis who do not have a history of CVEs.⁴ Tumor necrosis factor α is one of the major cytokines playing a role in the inflammatory process of psoriasis. Studies have shown serum levels of tumor necrosis factor α to correlate with the clinical symptoms of heart failure and to supraventricular arrhythmia in animal models.⁴ Various extreme CVEs can be an expression of this ongoing dynamic process. It would be interesting to know which specific factors among these inflammatory cytokines lead to rhythm irregularities.

Another theory is that young patients may experience micro-MI during the disease course. These small infarcted areas may act as aberrant pulse generators or lead to conduction disturbances. One study found increased correct QT interval dispersion, a predictor of ventricular arrhythmias, to be associated with psoriasis.⁵ A nationwide population-based matched cohort study by Chiu et al⁶ revealed that patients with psoriasis have a higher risk for arrhythmia independent of traditional cardiovascular risk factors. Our patient also had severe unstable psoriasis for 8 years that may have led to increased accumulation of proarrhythmogenic cytokines in the heart and could have led to VT.

Acitretin as a potential cause of sudden cardiac death remains a possibility in our case; however, the exact mechanism leading to such sudden arrhythmia is lacking. Acitretin is known to increase serum triglycerides and cholesterol, specifically by shifting high-density lipoproteins to low-density lipoproteins, thereby increasing the risk for CVE. However, it takes time for such derangement to occur, eventually leading to CVE. Mittal et al⁷ reported a psoriasis patient who died secondary to MI after 5 days of low-dose acitretin. Lack of evidence makes acitretin a less likely cause of mortality.

We present a case of sudden cardiac death secondary to VT in a young patient with psoriasis and no other traditional cardiovascular risk factors. This case highlights the importance of being vigilant for adverse CVEs such as arrhythmia in psoriatic patients, especially in younger patients with severe unstable disease.

To the Editor:

We report the case of an 83-year-old male nursing home resident with a history of end-stage renal disease who presented with multiple small white islands on the surface of the nail plate, similar to those seen in white superficial onychomycosis (Figure 1). Minimal subungual hyperkeratosis of the fingernails also was observed. Three digits were affected with no toenail involvement. Wet mount examination with potassium hydroxide 20% showed a mite (Figure 2A) and multiple eggs (Figure 2B). Treatment consisted of oral ivermectin 3 mg immediately and permethrin solution 5% applied under occlusion to each of the affected nails for 5 consecutive nights, which resulted in complete clearance of the lesion on the nail plate after 2 weeks.

Crusted scabies was first described as Norwegian scabies in 1848 by Danielsen and Boeck,¹ and the name was later changed to crusted scabies in 1976 by Parish and Lumholt² because there was no inherent connection between Norway and Norwegian scabies. It is a skin infestation of Sarcoptes scabiei var hominis and more commonly is seen in immunocompromised individuals such as the elderly and malnourished patients as well as those with diabetes mellitus and alcoholism.^3,4 Patients typically present with widespread hyperkeratosis, mostly involving the palms and soles. Subungual hyperkeratosis and nail dystrophy also can be seen when nail involvement is present, and the scalp rarely is involved.⁵ Unlike common scabies, skin burrows and pruritus may be minimal or absent, thus making the diagnosis of crusted scabies more difficult than normal scabies.⁶ Diagnosis of crusted scabies is confirmed by direct microscopy, which demonstrates mites, eggs, or feces. Strict isolation of the patient is necessary, as the disease is very contagious. Treatment with oral ivermectin (1–3 doses of 3 mg at 14-day intervals) in combination with topical permethrin is effective.⁷

We present a case of crusted scabies with nail involvement that presented with white superficial onychomycosislike lesions. The patient’s nails were successfully treated with a combination of oral ivermectin and topical permethrin occlusion of the nails. In cases with subungual hyperkeratosis, nonsurgical nail avulsion with 40% urea cream or ointment has been used to improve the penetration of permethrin. Partial nail avulsion may be necessary if subungual hyperkeratosis or nail dystrophy becomes extreme.⁸

To the Editor:

We report the case of an 83-year-old male nursing home resident with a history of end-stage renal disease who presented with multiple small white islands on the surface of the nail plate, similar to those seen in white superficial onychomycosis (Figure 1). Minimal subungual hyperkeratosis of the fingernails also was observed. Three digits were affected with no toenail involvement. Wet mount examination with potassium hydroxide 20% showed a mite (Figure 2A) and multiple eggs (Figure 2B). Treatment consisted of oral ivermectin 3 mg immediately and permethrin solution 5% applied under occlusion to each of the affected nails for 5 consecutive nights, which resulted in complete clearance of the lesion on the nail plate after 2 weeks.

Crusted scabies was first described as Norwegian scabies in 1848 by Danielsen and Boeck,¹ and the name was later changed to crusted scabies in 1976 by Parish and Lumholt² because there was no inherent connection between Norway and Norwegian scabies. It is a skin infestation of Sarcoptes scabiei var hominis and more commonly is seen in immunocompromised individuals such as the elderly and malnourished patients as well as those with diabetes mellitus and alcoholism.^3,4 Patients typically present with widespread hyperkeratosis, mostly involving the palms and soles. Subungual hyperkeratosis and nail dystrophy also can be seen when nail involvement is present, and the scalp rarely is involved.⁵ Unlike common scabies, skin burrows and pruritus may be minimal or absent, thus making the diagnosis of crusted scabies more difficult than normal scabies.⁶ Diagnosis of crusted scabies is confirmed by direct microscopy, which demonstrates mites, eggs, or feces. Strict isolation of the patient is necessary, as the disease is very contagious. Treatment with oral ivermectin (1–3 doses of 3 mg at 14-day intervals) in combination with topical permethrin is effective.⁷

We present a case of crusted scabies with nail involvement that presented with white superficial onychomycosislike lesions. The patient’s nails were successfully treated with a combination of oral ivermectin and topical permethrin occlusion of the nails. In cases with subungual hyperkeratosis, nonsurgical nail avulsion with 40% urea cream or ointment has been used to improve the penetration of permethrin. Partial nail avulsion may be necessary if subungual hyperkeratosis or nail dystrophy becomes extreme.⁸

To the Editor:

We report the case of an 83-year-old male nursing home resident with a history of end-stage renal disease who presented with multiple small white islands on the surface of the nail plate, similar to those seen in white superficial onychomycosis (Figure 1). Minimal subungual hyperkeratosis of the fingernails also was observed. Three digits were affected with no toenail involvement. Wet mount examination with potassium hydroxide 20% showed a mite (Figure 2A) and multiple eggs (Figure 2B). Treatment consisted of oral ivermectin 3 mg immediately and permethrin solution 5% applied under occlusion to each of the affected nails for 5 consecutive nights, which resulted in complete clearance of the lesion on the nail plate after 2 weeks.

Crusted scabies was first described as Norwegian scabies in 1848 by Danielsen and Boeck,¹ and the name was later changed to crusted scabies in 1976 by Parish and Lumholt² because there was no inherent connection between Norway and Norwegian scabies. It is a skin infestation of Sarcoptes scabiei var hominis and more commonly is seen in immunocompromised individuals such as the elderly and malnourished patients as well as those with diabetes mellitus and alcoholism.^3,4 Patients typically present with widespread hyperkeratosis, mostly involving the palms and soles. Subungual hyperkeratosis and nail dystrophy also can be seen when nail involvement is present, and the scalp rarely is involved.⁵ Unlike common scabies, skin burrows and pruritus may be minimal or absent, thus making the diagnosis of crusted scabies more difficult than normal scabies.⁶ Diagnosis of crusted scabies is confirmed by direct microscopy, which demonstrates mites, eggs, or feces. Strict isolation of the patient is necessary, as the disease is very contagious. Treatment with oral ivermectin (1–3 doses of 3 mg at 14-day intervals) in combination with topical permethrin is effective.⁷

We present a case of crusted scabies with nail involvement that presented with white superficial onychomycosislike lesions. The patient’s nails were successfully treated with a combination of oral ivermectin and topical permethrin occlusion of the nails. In cases with subungual hyperkeratosis, nonsurgical nail avulsion with 40% urea cream or ointment has been used to improve the penetration of permethrin. Partial nail avulsion may be necessary if subungual hyperkeratosis or nail dystrophy becomes extreme.⁸

To the Editor:

A 28-year-old man presented to the dermatology clinic with red, tender, swollen nodules on the left arm of 5 days’ duration, which had been a recurrent issue involving both arms. He also experienced intermittent fatigue and mild myalgia but denied associated fevers or chills. Oral clindamycin prescribed by a local emergency department provided some improvement. Upon further questioning, the patient admitted to injecting an unknown substance into the muscles 10 years prior for the purpose of enhancing their volume and appearance. Physical examination revealed large bilateral biceps with firm, mobile, nontender, subcutaneous nodules and mild erythema on the inner aspects of the arms. An incisional biopsy of a left arm nodule was performed with tissue culture (Figure 1). Microscopic evaluation revealed mild dermal sclerosis with edema and sclerosis of fat septae (Figure 2A). The fat lobules contained granulomas with surrounding lymphocytes and clear holes noted within the histiocytic giant cells, indicating a likely foreign substance (Figure 2B). Immunohistochemical staining of the histiocytes with CD68 highlighted the clear vacuoles (Figure 3). Polarization examination, Alcian blue, periodic acid–Schiff, and acid-fast bacilli staining were negative. Bacterial, fungal, and mycobacterial tissue cultures and staining also were negative. The histologic findings of septal and lobular panniculitis with sclerosis and granulomatous inflammation in the clinical setting were consistent with a foreign body reaction secondary to synthol injection.

The willingness of athletes in competitive sports to undergo procedures or utilize substances for a competitive advantage despite both immediate and long-term consequences is well documented.^1,2 In bodybuilding, use of anabolic steroids and intramuscular oil injections has been documented.³ The use of site enhancements in the form of “fillers” such as petroleum jelly and paraffin have been used for more than 100 years.⁴ The use of oil for volumetric site enhancement began in the 1960s in Italy with formebolone and evolved to the use of synthol in the 1990s.⁵ Synthol is a substance composed of 85% oil in the form of medium-chain triglycerides, 7.5% alcohol, and 7.5% lidocaine.⁶ The presumed mechanism of action of injected oils consists of an initial inflammatory response followed by fibrosis and chronic macrophagocytosis, ultimately leading to expanded volume in the subcutaneous tissue.⁷ These procedures are purely aesthetic with no increase in muscle strength or performance.

There are few cases in the literature of side effects from intramuscular synthol injections. In one report, a 29-year-old man presented with painful muscle fibrosis requiring open surgical excision of massively fibrotic bicep tissue.⁸ Another report documented a 45-year-old man who presented with spontaneous ulcerations on the biceps that initially were treated with antibiotics and compression therapy but eventually required surgical intervention and skin grafting.⁹ Complications have been more frequently reported from injections of other oils such as paraffin and sesame.^10,11 Given the similar underlying mechanisms of action, injected oils share the local side effects of inflammation, infection, chronic wounds, and ulceration,^9,10 as well as a systemic risk for embolization leading to pulmonary emboli, myocardial infarction, and stroke.⁶ Although no standard of care exists for the management of complications arising from intramuscular oil injections, treatments that have been employed include antibiotics, corticosteroids, wound care, and compression therapy; definitive treatment typically is surgical excision.^6,8,9,11,12 Psychiatric evaluation also should be considered to evaluate for the possibility of body dysmorphic disorder and other associated psychiatric conditions.¹¹

Pressure for a particular aesthetic appearance, both within and outside the world of competitive sports, has driven individuals to various methods of muscular enhancement. Volumetric site enhancements have become increasingly popular, in part due to the perceived lack of systemic side effects, such as those associated with anabolic steroids.⁸ However, most users are unaware of the notable short-term and long-term risks associated with intramuscular oil injections. Synthol is widely available on the Internet and easily can be purchased and injected by anyone.¹³ Medical providers should be aware of the possibility of aesthetic site enhancement use in their patients and be able to recognize and intervene in these cases to prevent chronic damage to muscle tissue and accompanying complications. Despite extensive commercialization of these products, few reports in the medical literature exist detailing the side effects of intramuscular oil injections, which may be contributing to the trivialization of these procedures by the general public.¹²

To the Editor:

A 28-year-old man presented to the dermatology clinic with red, tender, swollen nodules on the left arm of 5 days’ duration, which had been a recurrent issue involving both arms. He also experienced intermittent fatigue and mild myalgia but denied associated fevers or chills. Oral clindamycin prescribed by a local emergency department provided some improvement. Upon further questioning, the patient admitted to injecting an unknown substance into the muscles 10 years prior for the purpose of enhancing their volume and appearance. Physical examination revealed large bilateral biceps with firm, mobile, nontender, subcutaneous nodules and mild erythema on the inner aspects of the arms. An incisional biopsy of a left arm nodule was performed with tissue culture (Figure 1). Microscopic evaluation revealed mild dermal sclerosis with edema and sclerosis of fat septae (Figure 2A). The fat lobules contained granulomas with surrounding lymphocytes and clear holes noted within the histiocytic giant cells, indicating a likely foreign substance (Figure 2B). Immunohistochemical staining of the histiocytes with CD68 highlighted the clear vacuoles (Figure 3). Polarization examination, Alcian blue, periodic acid–Schiff, and acid-fast bacilli staining were negative. Bacterial, fungal, and mycobacterial tissue cultures and staining also were negative. The histologic findings of septal and lobular panniculitis with sclerosis and granulomatous inflammation in the clinical setting were consistent with a foreign body reaction secondary to synthol injection.

The willingness of athletes in competitive sports to undergo procedures or utilize substances for a competitive advantage despite both immediate and long-term consequences is well documented.^1,2 In bodybuilding, use of anabolic steroids and intramuscular oil injections has been documented.³ The use of site enhancements in the form of “fillers” such as petroleum jelly and paraffin have been used for more than 100 years.⁴ The use of oil for volumetric site enhancement began in the 1960s in Italy with formebolone and evolved to the use of synthol in the 1990s.⁵ Synthol is a substance composed of 85% oil in the form of medium-chain triglycerides, 7.5% alcohol, and 7.5% lidocaine.⁶ The presumed mechanism of action of injected oils consists of an initial inflammatory response followed by fibrosis and chronic macrophagocytosis, ultimately leading to expanded volume in the subcutaneous tissue.⁷ These procedures are purely aesthetic with no increase in muscle strength or performance.

There are few cases in the literature of side effects from intramuscular synthol injections. In one report, a 29-year-old man presented with painful muscle fibrosis requiring open surgical excision of massively fibrotic bicep tissue.⁸ Another report documented a 45-year-old man who presented with spontaneous ulcerations on the biceps that initially were treated with antibiotics and compression therapy but eventually required surgical intervention and skin grafting.⁹ Complications have been more frequently reported from injections of other oils such as paraffin and sesame.^10,11 Given the similar underlying mechanisms of action, injected oils share the local side effects of inflammation, infection, chronic wounds, and ulceration,^9,10 as well as a systemic risk for embolization leading to pulmonary emboli, myocardial infarction, and stroke.⁶ Although no standard of care exists for the management of complications arising from intramuscular oil injections, treatments that have been employed include antibiotics, corticosteroids, wound care, and compression therapy; definitive treatment typically is surgical excision.^6,8,9,11,12 Psychiatric evaluation also should be considered to evaluate for the possibility of body dysmorphic disorder and other associated psychiatric conditions.¹¹

Pressure for a particular aesthetic appearance, both within and outside the world of competitive sports, has driven individuals to various methods of muscular enhancement. Volumetric site enhancements have become increasingly popular, in part due to the perceived lack of systemic side effects, such as those associated with anabolic steroids.⁸ However, most users are unaware of the notable short-term and long-term risks associated with intramuscular oil injections. Synthol is widely available on the Internet and easily can be purchased and injected by anyone.¹³ Medical providers should be aware of the possibility of aesthetic site enhancement use in their patients and be able to recognize and intervene in these cases to prevent chronic damage to muscle tissue and accompanying complications. Despite extensive commercialization of these products, few reports in the medical literature exist detailing the side effects of intramuscular oil injections, which may be contributing to the trivialization of these procedures by the general public.¹²

To the Editor:

A 28-year-old man presented to the dermatology clinic with red, tender, swollen nodules on the left arm of 5 days’ duration, which had been a recurrent issue involving both arms. He also experienced intermittent fatigue and mild myalgia but denied associated fevers or chills. Oral clindamycin prescribed by a local emergency department provided some improvement. Upon further questioning, the patient admitted to injecting an unknown substance into the muscles 10 years prior for the purpose of enhancing their volume and appearance. Physical examination revealed large bilateral biceps with firm, mobile, nontender, subcutaneous nodules and mild erythema on the inner aspects of the arms. An incisional biopsy of a left arm nodule was performed with tissue culture (Figure 1). Microscopic evaluation revealed mild dermal sclerosis with edema and sclerosis of fat septae (Figure 2A). The fat lobules contained granulomas with surrounding lymphocytes and clear holes noted within the histiocytic giant cells, indicating a likely foreign substance (Figure 2B). Immunohistochemical staining of the histiocytes with CD68 highlighted the clear vacuoles (Figure 3). Polarization examination, Alcian blue, periodic acid–Schiff, and acid-fast bacilli staining were negative. Bacterial, fungal, and mycobacterial tissue cultures and staining also were negative. The histologic findings of septal and lobular panniculitis with sclerosis and granulomatous inflammation in the clinical setting were consistent with a foreign body reaction secondary to synthol injection.

The willingness of athletes in competitive sports to undergo procedures or utilize substances for a competitive advantage despite both immediate and long-term consequences is well documented.^1,2 In bodybuilding, use of anabolic steroids and intramuscular oil injections has been documented.³ The use of site enhancements in the form of “fillers” such as petroleum jelly and paraffin have been used for more than 100 years.⁴ The use of oil for volumetric site enhancement began in the 1960s in Italy with formebolone and evolved to the use of synthol in the 1990s.⁵ Synthol is a substance composed of 85% oil in the form of medium-chain triglycerides, 7.5% alcohol, and 7.5% lidocaine.⁶ The presumed mechanism of action of injected oils consists of an initial inflammatory response followed by fibrosis and chronic macrophagocytosis, ultimately leading to expanded volume in the subcutaneous tissue.⁷ These procedures are purely aesthetic with no increase in muscle strength or performance.

There are few cases in the literature of side effects from intramuscular synthol injections. In one report, a 29-year-old man presented with painful muscle fibrosis requiring open surgical excision of massively fibrotic bicep tissue.⁸ Another report documented a 45-year-old man who presented with spontaneous ulcerations on the biceps that initially were treated with antibiotics and compression therapy but eventually required surgical intervention and skin grafting.⁹ Complications have been more frequently reported from injections of other oils such as paraffin and sesame.^10,11 Given the similar underlying mechanisms of action, injected oils share the local side effects of inflammation, infection, chronic wounds, and ulceration,^9,10 as well as a systemic risk for embolization leading to pulmonary emboli, myocardial infarction, and stroke.⁶ Although no standard of care exists for the management of complications arising from intramuscular oil injections, treatments that have been employed include antibiotics, corticosteroids, wound care, and compression therapy; definitive treatment typically is surgical excision.^6,8,9,11,12 Psychiatric evaluation also should be considered to evaluate for the possibility of body dysmorphic disorder and other associated psychiatric conditions.¹¹

Pressure for a particular aesthetic appearance, both within and outside the world of competitive sports, has driven individuals to various methods of muscular enhancement. Volumetric site enhancements have become increasingly popular, in part due to the perceived lack of systemic side effects, such as those associated with anabolic steroids.⁸ However, most users are unaware of the notable short-term and long-term risks associated with intramuscular oil injections. Synthol is widely available on the Internet and easily can be purchased and injected by anyone.¹³ Medical providers should be aware of the possibility of aesthetic site enhancement use in their patients and be able to recognize and intervene in these cases to prevent chronic damage to muscle tissue and accompanying complications. Despite extensive commercialization of these products, few reports in the medical literature exist detailing the side effects of intramuscular oil injections, which may be contributing to the trivialization of these procedures by the general public.¹²

To the Editor:

The transient and generic appearance of exercise-induced vasculitis (EIV) makes it a commonly misdiagnosed condition. The lesion often is only encountered through photographs brought by the patient or by taking a thorough history. The lack of findings on clinical inspection and the generic appearance of EIV may lead to misdiagnosis as stasis dermatitis due to its presentation as erythematous lesions on the medial lower legs.

A 68-year-old woman with no notable medical history was referred to our clinic for suspected stasis dermatitis. At presentation, no lesions were identified on the legs, but she brought photographs of an erythematous urticarial eruption on the medial lower legs, extending from just above the sock line to the mid-calves (Figure). The eruptions had occurred over the last 16 years, typically presenting suddenly after playing tennis or an extended period of walking and spontaneously resolving in 4 days. The lesions were painless, restricted to the calves, and were not pruritic, though the initial presentation 16 years prior included pruritic pigmented patches on the anterior thighs. Because the condition spontaneously improved within days, no treatment was attempted. An ultrasound venous reflux study ruled out venous reflux and stasis dermatitis.

Histologic examination demonstrates features of leukocytoclastic vasculitis with perivascular lymphocytic and neutrophilic infiltrates.² Erythrocyte extravasation, IgM deposits, and identification of C3 also have been reported.^8,9 The spontaneous resolution of EIV has led to treatment efforts being focused on preventative measures. Several cases have reported some degree of success in preventing EIV with compression therapy, venoactive drugs, systemic steroids, and application of topical steroids before exercise.³

The clinical morphology and lower leg location of EIV leads to a common misdiagnosis of stasis dermatitis. Clinical history of a transient nature is the mainstay in the diagnosis of EIV, and ultrasound venous reflux study may be required in some cases. Preventative measures are superior to treatment and mainly include compression therapy.

To the Editor:

The transient and generic appearance of exercise-induced vasculitis (EIV) makes it a commonly misdiagnosed condition. The lesion often is only encountered through photographs brought by the patient or by taking a thorough history. The lack of findings on clinical inspection and the generic appearance of EIV may lead to misdiagnosis as stasis dermatitis due to its presentation as erythematous lesions on the medial lower legs.

A 68-year-old woman with no notable medical history was referred to our clinic for suspected stasis dermatitis. At presentation, no lesions were identified on the legs, but she brought photographs of an erythematous urticarial eruption on the medial lower legs, extending from just above the sock line to the mid-calves (Figure). The eruptions had occurred over the last 16 years, typically presenting suddenly after playing tennis or an extended period of walking and spontaneously resolving in 4 days. The lesions were painless, restricted to the calves, and were not pruritic, though the initial presentation 16 years prior included pruritic pigmented patches on the anterior thighs. Because the condition spontaneously improved within days, no treatment was attempted. An ultrasound venous reflux study ruled out venous reflux and stasis dermatitis.

Histologic examination demonstrates features of leukocytoclastic vasculitis with perivascular lymphocytic and neutrophilic infiltrates.² Erythrocyte extravasation, IgM deposits, and identification of C3 also have been reported.^8,9 The spontaneous resolution of EIV has led to treatment efforts being focused on preventative measures. Several cases have reported some degree of success in preventing EIV with compression therapy, venoactive drugs, systemic steroids, and application of topical steroids before exercise.³

The clinical morphology and lower leg location of EIV leads to a common misdiagnosis of stasis dermatitis. Clinical history of a transient nature is the mainstay in the diagnosis of EIV, and ultrasound venous reflux study may be required in some cases. Preventative measures are superior to treatment and mainly include compression therapy.

To the Editor:

The transient and generic appearance of exercise-induced vasculitis (EIV) makes it a commonly misdiagnosed condition. The lesion often is only encountered through photographs brought by the patient or by taking a thorough history. The lack of findings on clinical inspection and the generic appearance of EIV may lead to misdiagnosis as stasis dermatitis due to its presentation as erythematous lesions on the medial lower legs.

A 68-year-old woman with no notable medical history was referred to our clinic for suspected stasis dermatitis. At presentation, no lesions were identified on the legs, but she brought photographs of an erythematous urticarial eruption on the medial lower legs, extending from just above the sock line to the mid-calves (Figure). The eruptions had occurred over the last 16 years, typically presenting suddenly after playing tennis or an extended period of walking and spontaneously resolving in 4 days. The lesions were painless, restricted to the calves, and were not pruritic, though the initial presentation 16 years prior included pruritic pigmented patches on the anterior thighs. Because the condition spontaneously improved within days, no treatment was attempted. An ultrasound venous reflux study ruled out venous reflux and stasis dermatitis.

Histologic examination demonstrates features of leukocytoclastic vasculitis with perivascular lymphocytic and neutrophilic infiltrates.² Erythrocyte extravasation, IgM deposits, and identification of C3 also have been reported.^8,9 The spontaneous resolution of EIV has led to treatment efforts being focused on preventative measures. Several cases have reported some degree of success in preventing EIV with compression therapy, venoactive drugs, systemic steroids, and application of topical steroids before exercise.³

The clinical morphology and lower leg location of EIV leads to a common misdiagnosis of stasis dermatitis. Clinical history of a transient nature is the mainstay in the diagnosis of EIV, and ultrasound venous reflux study may be required in some cases. Preventative measures are superior to treatment and mainly include compression therapy.

To the Editor:

Few cases of unilateral nail changes affecting only the hemiplegic side after a stroke have been reported. We present a case of acquired unilateral nail clubbing and longitudinal melanonychia in a hemiparetic patient.

A 79-year-old Black man with a history of smoking and stroke presented with concerns of discoloration of the fingernails. His medical history was notable for congestive heart failure; hypertension; diabetes mellitus; hypercholesterolemia; and stroke 11 years prior, which resulted in right-sided hemiparesis. Physical examination revealed longitudinal, even hyperpigmentation of several fingernails on the hands, in addition to whitening of the nail beds, sparing the tips (Terry nails). Clubbing was noted only on the fingernails of the right hand; the fingernails of the left hand exhibited normal curvature (Figure). Pulse oximetry was conducted and demonstrated the following readings: unaffected left index finger, 98%; unaffected left middle finger, 100%; affected right index finger, 95%; and affected right middle finger, 97%. The patient was diagnosed with benign longitudinal melanonychia secondary to ethnic variation, Terry nails without underlying anemia or hypoalbuminemic state, and unilateral right-sided clubbing of the fingernails in the setting of right-sided hemiparesis.

Digital clubbing describes an exaggerated nail curvature and bulbous overgrowth of the fingertips due to an expansion of connective tissue between the nail plate and the nail bed.^3,5 Clubbed fingers are found in various chronic conditions affecting the heart, lungs, and liver. Although the pathogenesis of clubbing remains unknown, many hypothesize that it is a state of proliferation in response to digital hypoxia.⁵ Fittingly, our patient exhibited a relative hypoperfusion of the clubbed fingers in comparison to the unaffected side.

This case provides additional support for the phenomenon of unilateral nail changes limited to hemiplegic or hemiparetic limbs. The unique presentation of longitudinal melanonychia, clubbing, and a lowered pulse oximetry reading only affecting the hemiparetic side demonstrates the possible connection between hypoxia and nail clubbing in this patient population.

To the Editor:

Few cases of unilateral nail changes affecting only the hemiplegic side after a stroke have been reported. We present a case of acquired unilateral nail clubbing and longitudinal melanonychia in a hemiparetic patient.

A 79-year-old Black man with a history of smoking and stroke presented with concerns of discoloration of the fingernails. His medical history was notable for congestive heart failure; hypertension; diabetes mellitus; hypercholesterolemia; and stroke 11 years prior, which resulted in right-sided hemiparesis. Physical examination revealed longitudinal, even hyperpigmentation of several fingernails on the hands, in addition to whitening of the nail beds, sparing the tips (Terry nails). Clubbing was noted only on the fingernails of the right hand; the fingernails of the left hand exhibited normal curvature (Figure). Pulse oximetry was conducted and demonstrated the following readings: unaffected left index finger, 98%; unaffected left middle finger, 100%; affected right index finger, 95%; and affected right middle finger, 97%. The patient was diagnosed with benign longitudinal melanonychia secondary to ethnic variation, Terry nails without underlying anemia or hypoalbuminemic state, and unilateral right-sided clubbing of the fingernails in the setting of right-sided hemiparesis.

Digital clubbing describes an exaggerated nail curvature and bulbous overgrowth of the fingertips due to an expansion of connective tissue between the nail plate and the nail bed.^3,5 Clubbed fingers are found in various chronic conditions affecting the heart, lungs, and liver. Although the pathogenesis of clubbing remains unknown, many hypothesize that it is a state of proliferation in response to digital hypoxia.⁵ Fittingly, our patient exhibited a relative hypoperfusion of the clubbed fingers in comparison to the unaffected side.

This case provides additional support for the phenomenon of unilateral nail changes limited to hemiplegic or hemiparetic limbs. The unique presentation of longitudinal melanonychia, clubbing, and a lowered pulse oximetry reading only affecting the hemiparetic side demonstrates the possible connection between hypoxia and nail clubbing in this patient population.

To the Editor:

Few cases of unilateral nail changes affecting only the hemiplegic side after a stroke have been reported. We present a case of acquired unilateral nail clubbing and longitudinal melanonychia in a hemiparetic patient.

A 79-year-old Black man with a history of smoking and stroke presented with concerns of discoloration of the fingernails. His medical history was notable for congestive heart failure; hypertension; diabetes mellitus; hypercholesterolemia; and stroke 11 years prior, which resulted in right-sided hemiparesis. Physical examination revealed longitudinal, even hyperpigmentation of several fingernails on the hands, in addition to whitening of the nail beds, sparing the tips (Terry nails). Clubbing was noted only on the fingernails of the right hand; the fingernails of the left hand exhibited normal curvature (Figure). Pulse oximetry was conducted and demonstrated the following readings: unaffected left index finger, 98%; unaffected left middle finger, 100%; affected right index finger, 95%; and affected right middle finger, 97%. The patient was diagnosed with benign longitudinal melanonychia secondary to ethnic variation, Terry nails without underlying anemia or hypoalbuminemic state, and unilateral right-sided clubbing of the fingernails in the setting of right-sided hemiparesis.

Digital clubbing describes an exaggerated nail curvature and bulbous overgrowth of the fingertips due to an expansion of connective tissue between the nail plate and the nail bed.^3,5 Clubbed fingers are found in various chronic conditions affecting the heart, lungs, and liver. Although the pathogenesis of clubbing remains unknown, many hypothesize that it is a state of proliferation in response to digital hypoxia.⁵ Fittingly, our patient exhibited a relative hypoperfusion of the clubbed fingers in comparison to the unaffected side.

This case provides additional support for the phenomenon of unilateral nail changes limited to hemiplegic or hemiparetic limbs. The unique presentation of longitudinal melanonychia, clubbing, and a lowered pulse oximetry reading only affecting the hemiparetic side demonstrates the possible connection between hypoxia and nail clubbing in this patient population.

To the Editor:

Bullous pemphigoid (BP) is a rare complication of lower limb amputation. Termed stump pemphigoid, it previously was described as a late complication arising on the stumps of leg amputees and tends to remain localized. We describe a case of stump pemphigoid presenting with an urticarial prodromal phase without generalized progression, confirmed by serum assay for circulating anti–basement membrane antibodies.

A 62-year-old man with a history of a right above-knee amputation initially presented with erythema as well as coalescing erosions and ulcers with fluid-filled vesicles and bullae on the amputation stump (Figure 1). The amputation was performed 15 years prior after a motorcycle accident. A skin biopsy of a vesicle on the amputation stump revealed subepidermal and focal intraepidermal clefting with hemorrhage and rare inflammatory cells composed of neutrophils and eosinophils (Figure 2). A tissue direct immunofluorescence test demonstrated linear C3 and IgG deposition along the dermoepidermal junction. Serum enzyme-linked immunosorbent assay (ELISA) demonstrated an anti-BP180 IgG of 50.90 U/mL and anti-BP230 IgG of 129.40 U/mL (reference range, <9.00 U/mL [for both]).

Amputees experience a high rate of skin complications on their stump,¹ including friction blisters, shear injury, contact dermatitis, infections, and autoimmune blistering disorders (ie, BP, epidermolysis bullosa acquisita). The etiology of stump pemphigoid is not entirely understood but could be related to exposure of structural components of the hemidesmosome (eg, BP230, BP180), leading to autoantibody production as a consequence of either the underlying limb injury or from recurrent trauma related to limb prosthetics.²

Two previously reported cases of stump pemphigoid demonstrated a positive direct immunofluorescence antibody test.^3,4 Another case demonstrated the presence of circulating IgG antibodies on indirect immunofluorescence to salt-split skin.⁵ We report a case of stump pemphigoid confirmed by presence of circulating anti–basement membrane antibodies on ELISA, supporting its use in the diagnostic workup and monitoring treatment response.

To the Editor:

Bullous pemphigoid (BP) is a rare complication of lower limb amputation. Termed stump pemphigoid, it previously was described as a late complication arising on the stumps of leg amputees and tends to remain localized. We describe a case of stump pemphigoid presenting with an urticarial prodromal phase without generalized progression, confirmed by serum assay for circulating anti–basement membrane antibodies.

A 62-year-old man with a history of a right above-knee amputation initially presented with erythema as well as coalescing erosions and ulcers with fluid-filled vesicles and bullae on the amputation stump (Figure 1). The amputation was performed 15 years prior after a motorcycle accident. A skin biopsy of a vesicle on the amputation stump revealed subepidermal and focal intraepidermal clefting with hemorrhage and rare inflammatory cells composed of neutrophils and eosinophils (Figure 2). A tissue direct immunofluorescence test demonstrated linear C3 and IgG deposition along the dermoepidermal junction. Serum enzyme-linked immunosorbent assay (ELISA) demonstrated an anti-BP180 IgG of 50.90 U/mL and anti-BP230 IgG of 129.40 U/mL (reference range, <9.00 U/mL [for both]).

Amputees experience a high rate of skin complications on their stump,¹ including friction blisters, shear injury, contact dermatitis, infections, and autoimmune blistering disorders (ie, BP, epidermolysis bullosa acquisita). The etiology of stump pemphigoid is not entirely understood but could be related to exposure of structural components of the hemidesmosome (eg, BP230, BP180), leading to autoantibody production as a consequence of either the underlying limb injury or from recurrent trauma related to limb prosthetics.²

Two previously reported cases of stump pemphigoid demonstrated a positive direct immunofluorescence antibody test.^3,4 Another case demonstrated the presence of circulating IgG antibodies on indirect immunofluorescence to salt-split skin.⁵ We report a case of stump pemphigoid confirmed by presence of circulating anti–basement membrane antibodies on ELISA, supporting its use in the diagnostic workup and monitoring treatment response.

To the Editor:

Bullous pemphigoid (BP) is a rare complication of lower limb amputation. Termed stump pemphigoid, it previously was described as a late complication arising on the stumps of leg amputees and tends to remain localized. We describe a case of stump pemphigoid presenting with an urticarial prodromal phase without generalized progression, confirmed by serum assay for circulating anti–basement membrane antibodies.

A 62-year-old man with a history of a right above-knee amputation initially presented with erythema as well as coalescing erosions and ulcers with fluid-filled vesicles and bullae on the amputation stump (Figure 1). The amputation was performed 15 years prior after a motorcycle accident. A skin biopsy of a vesicle on the amputation stump revealed subepidermal and focal intraepidermal clefting with hemorrhage and rare inflammatory cells composed of neutrophils and eosinophils (Figure 2). A tissue direct immunofluorescence test demonstrated linear C3 and IgG deposition along the dermoepidermal junction. Serum enzyme-linked immunosorbent assay (ELISA) demonstrated an anti-BP180 IgG of 50.90 U/mL and anti-BP230 IgG of 129.40 U/mL (reference range, <9.00 U/mL [for both]).

Amputees experience a high rate of skin complications on their stump,¹ including friction blisters, shear injury, contact dermatitis, infections, and autoimmune blistering disorders (ie, BP, epidermolysis bullosa acquisita). The etiology of stump pemphigoid is not entirely understood but could be related to exposure of structural components of the hemidesmosome (eg, BP230, BP180), leading to autoantibody production as a consequence of either the underlying limb injury or from recurrent trauma related to limb prosthetics.²

Two previously reported cases of stump pemphigoid demonstrated a positive direct immunofluorescence antibody test.^3,4 Another case demonstrated the presence of circulating IgG antibodies on indirect immunofluorescence to salt-split skin.⁵ We report a case of stump pemphigoid confirmed by presence of circulating anti–basement membrane antibodies on ELISA, supporting its use in the diagnostic workup and monitoring treatment response.

To the Editor:

Scrub typhus (ST) is an infection caused by Orientia tsutsugamushi (genus Rickettsia), which is transmitted by the larvae of trombiculid mites, commonly called chiggers. The disease mainly has been described in Asia in an area known as the Tsutsugamushi Triangle, delineated by Pakistan, eastern Russia, and northern Australia. Although this classic distribution remains, recent reports have documented 1 case in the Arabian Peninsula¹ and more than 16 cases in southern Chile.^2-4 The first case in Chile was published in 2011 from Chiloé Island.² To date, no other cases have been reported in the Americas.^1-6

We describe a new case of ST from Chiloé Island and compare it to the first case reported in Chile in 2011.² Both patients showed the typical clinical manifestation, but because ST has become an increasingly suspected disease in southern regions of Chile, new cases are now easily diagnosed. This infection is diagnosed mainly by skin lesions; therefore, dermatologists should be aware of this diagnosis when presented with a febrile rash.

A 67-year-old man from the city of Punta Arenas presented to the emergency department with a dark necrotic lesion on the right foot of 1 week’s duration. The patient later developed a generalized pruritic rash and fever. He also reported muscle pain, headache, cough, night sweats, and odynophagia. He reported recent travel to a rural area in the northern part of Chiloé Island, where he came into contact with firewood and participated in outdoor activities. He had no other relevant medical history.

Physical examination revealed a temperature of 38 °C and a macular rash, with some papules distributed mainly on the face, trunk, and proximal extremities (Figure 1). He had a necrotic eschar on the dorsum of the right foot, with an erythematous halo (tache noire)(Figure 2).

Scrub typhus is a high-impact disease in Asia, described mainly in an area known as the Tsutsugamushi Triangle. Recent reports show important epidemiologic changes in the distribution of the disease, with new published reports of cases outside this endemic area—1 in the Arabian peninsula¹ and more than 16 in southern Chile.^2-4

The disease begins with a painless, erythematous, and usually unnoticed papule at the site of the bite. After 48 to 72 hours, the papule changes to a necrotic form (tache noire), surrounded by a red halo that often is small, similar to a cigarette burn. This lesion is described in 20% to 90% of infected patients in different series.⁷ Two or 3 days later (1 to 3 weeks after exposure), high fever suddenly develops. Along with fever, a maculopapular rash distributed centrifugally develops, without compromise of the palms or soles. Patients frequently report headache and night sweating. Sometimes, ST is accompanied by muscle or joint pain, red eye, cough, and abdominal pain. Hearing loss and altered mental status less frequently have been reported.^5,8

Common laboratory tests can be of use in diagnosis. An elevated C-reactive protein level and a slight to moderate increase in hepatic transaminases should be expected. Thrombocytopenia, leukopenia, and elevation of the lactate dehydrogenase level less frequently are present.^5,9

Our case de1monstrated a typical presentation. The patient developed a febrile syndrome with a generalized rash and a tache noire–type eschar associated with muscle pain, headache, cough, night sweats, and odynophagia. Because of epidemiologic changes in the area, the familiar clinical findings, and laboratory confirmation, histologic studies were unnecessary. In cases in which the diagnosis is not evident, skin biopsy could be useful, as in the first case reported in Chile.²

In that first case, the patient initially was hospitalized because of a febrile syndrome; eventually, a necrotic eschar was noticed on his leg. He had been staying on Chiloé Island and reported being bitten by leeches on multiple occasions. Laboratory findings revealed only slightly raised levels of hepatic transaminases and alkaline phosphatase. After a more precise dermatologic evaluation, the eschar of a tache noire, combined with other clinical and laboratory findings, raised suspicion of ST. Because this entity had never been described in Chile, biopsy of the eschar was taken to consider other entities in the differential diagnosis. Biopsy showed necrotizing leukocytoclastic vasculitis in the dermis and subcutaneous tissue, perivascular inflammatory infiltrates comprising lymphocytes and macrophages, and rickettsial microorganisms inside endothelial cells under electron microscopic examination. The specimen was tested for the 16S ribosomal RNA Orientia gene; its presence confirmed the diagnosis.²

Classically, histology from the eschar shows signs of vasculitis and rickettsial microorganisms inside endothelial cells on electron microscopy.^2,10 More recent publications describe important necrotic changes within keratinocytes as well as an inflammatory infiltrate comprising antigen-presenting cells, monocytes, macrophages, and dendritic cells. Using high-resolution thin sections with confocal laser scanning microscopy and staining of specific monoclonal antibodies against 56 kDa type-specific surface antigens, the bacteria were found inside antigen-presenting cells, many of them located perivascularly or passing through the endothelium.¹¹

The causal agent in Asia is O tsutsugamushi, an obligate intracellular bacterium (genus Rickettsia). Orientia species are transmitted by larvae of trombiculid mites, commonly called chiggers. The reservoir is believed to be the same as with chiggers, in which some vertebrates become infected and trombiculid mites feed on them.¹² Recent studies of Chilean cases have revealed the presence of a novel Orientia species, Candidatus Orientia chiloensis and its vector, trombiculid mites from the Herpetacarus species, Quadraseta species, and Paratrombicula species genera.^13,14

A high seroprevalence of Orientia species in dogs was reported in the main cities of Chiloé Island. Rates were higher in rural settings and older dogs. Of 202 specimens, 21.3% were positive for IgG against Orientia species.¹⁵

In Chile, most cases of ST came from Chiloé Island; some reports of cases from continental Chilean regions have been published.⁶ Most cases have occurred in the context of activities that brought the patients in contact with plants and firewood in rural areas during the summer.^3-6

The diagnosis of ST is eminently clinical, based on the triad of fever, macular or papular rash, and an inoculation necrotic eschar. The diagnosis is supported by epidemiologic facts and fast recovery after treatment is initiated.¹⁶ Although the diagnosis can be established based on a quick recovery in endemic countries, in areas such as Chile where incidence and distribution are not completely known, it is better to confirm the diagnosis with laboratory tests without delaying treatment. Several testing options exist, including serologic techniques (immunofluorescence or enzyme-linked immunosorbent assay), culture, and detection of the genetic material of Orientia species by PCR. Usually, IgM titers initially are negative, and IgG testing requires paired samples (acute and convalescent) to demonstrate seroconversion and therefore acute infection.¹⁷ Because culture requires a highly specialized laboratory, it is not frequently used. Polymerase chain reaction is recognized as the best confirmation method due to its high sensitivity and because it remains positive for a few days after treatment has been initiated. The specimen of choice is the eschar because of its high bacterial load. The base of the scar and the buffy coat are useful specimens when the eschar is unavailable.^5,17-19

Due to potential complications of ST, empirical treatment with an antibiotic should be started based on clinical facts and never delayed because of diagnostic tests.¹⁸ Classically, ST is treated with a member of the tetracycline family, such as doxycycline, which provides a cure rate of 63% to 100% in ST.⁵

A 2017 systematic review of treatment options for this infection examined 11 studies from Southeast Asia, China, and South Korea (N=957).¹⁶ The review mainly compared doxycycline with azithromycin, chloramphenicol, and tetracycline. No significant difference in cure rate was noted in comparing doxycycline with any of the other 3 antibiotics; most of the studies examined were characterized by a moderate level of evidence. Regarding adverse effects, doxycycline showed a few more cases of gastrointestinal intolerance, and in 2 of 4 studies with chloramphenicol, patients presented with leukopenia.¹⁶ Several studies compared standard treatment (doxycycline) with rifampicin, telithromycin, erythromycin, and levofloxacin individually; similar cure rates were noted between doxycycline and each of those 4 agents.

Therapeutic failure in ST has been reported in several cases with the use of levofloxacin.²⁰ Evidence for this novel antibiotic is still insufficient. Further studies are needed before rifampicin, telithromycin, erythromycin, or levofloxacin can be considered as options.Scrub typhus usually resolves within a few weeks. Left untreated, the disease can cause complications such as pneumonia, meningoencephalitis, renal failure, and even multiorgan failure and death. Without treatment, mortality is variable. A 2015 systematic review of mortality from untreated ST showed, on average, mortality of 6% (range, 0%–70%).²¹ When ST is treated, mortality falls to 0% to 30%.²² Cases reported in Chile have neither been lethal nor presented with severe complications.^4,5

Scrub typhus is an infectious disease common in Asia, caused by O tsutsugamushi and transmitted by chiggers. It should be suspected when a febrile macular or papular rash and a tache noire appear. The diagnosis can be supported by laboratory findings, such as an elevated C-reactive protein level or a slight increase in the levels of hepatic transaminases, and response to treatment. The diagnosis is confirmed by serology or PCR of a specimen of the eschar. Empiric therapy with antibiotics is mandatory; doxycycline is the first option.

First described in Chile in 2011,² ST was seen in a patient in whom disease was suspected because of clinical characteristics, laboratory and histologic findings, absence of prior reporting in South America, and confirmation with PCR targeting the 16S ribosomal RNA Orientia gene from specimens of the eschar. By 2020, 60 cases have been confirmed in Chile, not all of them published; there are no other reported cases in South America.

When comparing the first case in Chile² with our case, we noted that both described classic clinical findings; however, the management approach and diagnostic challenges have evolved over time. Nowadays, ST is highly suspected, so it can be largely recognized and treated, which also provides better understanding of the nature of this disease in Chile. Because this infection is diagnosed mainly by characteristic cutaneous lesions, dermatologists should be aware of its epidemiology, clinical features, and transmission, and they should stay open to the possibility of this (until now) unusual diagnosis in South America.

Acknowledgments
The authors would like to thank the Chilean Rickettsia & Zoonosis Research Group (Thomas Weitzel, MD [Santiago, Chile]; Constanza Martínez-Valdebenito [Santiago, Chile]; and Gerardo Acosta-Jammet, DSc [Valdivia, Chile]), whose study in execution in the country allowed the detection of the case and confirmation by PCR. The authors also thank Juan Carlos Román, MD (Chiloé, Chile) who was part of the team that detected this case.

To the Editor:

Scrub typhus (ST) is an infection caused by Orientia tsutsugamushi (genus Rickettsia), which is transmitted by the larvae of trombiculid mites, commonly called chiggers. The disease mainly has been described in Asia in an area known as the Tsutsugamushi Triangle, delineated by Pakistan, eastern Russia, and northern Australia. Although this classic distribution remains, recent reports have documented 1 case in the Arabian Peninsula¹ and more than 16 cases in southern Chile.^2-4 The first case in Chile was published in 2011 from Chiloé Island.² To date, no other cases have been reported in the Americas.^1-6

We describe a new case of ST from Chiloé Island and compare it to the first case reported in Chile in 2011.² Both patients showed the typical clinical manifestation, but because ST has become an increasingly suspected disease in southern regions of Chile, new cases are now easily diagnosed. This infection is diagnosed mainly by skin lesions; therefore, dermatologists should be aware of this diagnosis when presented with a febrile rash.

A 67-year-old man from the city of Punta Arenas presented to the emergency department with a dark necrotic lesion on the right foot of 1 week’s duration. The patient later developed a generalized pruritic rash and fever. He also reported muscle pain, headache, cough, night sweats, and odynophagia. He reported recent travel to a rural area in the northern part of Chiloé Island, where he came into contact with firewood and participated in outdoor activities. He had no other relevant medical history.

Physical examination revealed a temperature of 38 °C and a macular rash, with some papules distributed mainly on the face, trunk, and proximal extremities (Figure 1). He had a necrotic eschar on the dorsum of the right foot, with an erythematous halo (tache noire)(Figure 2).

Scrub typhus is a high-impact disease in Asia, described mainly in an area known as the Tsutsugamushi Triangle. Recent reports show important epidemiologic changes in the distribution of the disease, with new published reports of cases outside this endemic area—1 in the Arabian peninsula¹ and more than 16 in southern Chile.^2-4

The disease begins with a painless, erythematous, and usually unnoticed papule at the site of the bite. After 48 to 72 hours, the papule changes to a necrotic form (tache noire), surrounded by a red halo that often is small, similar to a cigarette burn. This lesion is described in 20% to 90% of infected patients in different series.⁷ Two or 3 days later (1 to 3 weeks after exposure), high fever suddenly develops. Along with fever, a maculopapular rash distributed centrifugally develops, without compromise of the palms or soles. Patients frequently report headache and night sweating. Sometimes, ST is accompanied by muscle or joint pain, red eye, cough, and abdominal pain. Hearing loss and altered mental status less frequently have been reported.^5,8

Common laboratory tests can be of use in diagnosis. An elevated C-reactive protein level and a slight to moderate increase in hepatic transaminases should be expected. Thrombocytopenia, leukopenia, and elevation of the lactate dehydrogenase level less frequently are present.^5,9

Our case de1monstrated a typical presentation. The patient developed a febrile syndrome with a generalized rash and a tache noire–type eschar associated with muscle pain, headache, cough, night sweats, and odynophagia. Because of epidemiologic changes in the area, the familiar clinical findings, and laboratory confirmation, histologic studies were unnecessary. In cases in which the diagnosis is not evident, skin biopsy could be useful, as in the first case reported in Chile.²

In that first case, the patient initially was hospitalized because of a febrile syndrome; eventually, a necrotic eschar was noticed on his leg. He had been staying on Chiloé Island and reported being bitten by leeches on multiple occasions. Laboratory findings revealed only slightly raised levels of hepatic transaminases and alkaline phosphatase. After a more precise dermatologic evaluation, the eschar of a tache noire, combined with other clinical and laboratory findings, raised suspicion of ST. Because this entity had never been described in Chile, biopsy of the eschar was taken to consider other entities in the differential diagnosis. Biopsy showed necrotizing leukocytoclastic vasculitis in the dermis and subcutaneous tissue, perivascular inflammatory infiltrates comprising lymphocytes and macrophages, and rickettsial microorganisms inside endothelial cells under electron microscopic examination. The specimen was tested for the 16S ribosomal RNA Orientia gene; its presence confirmed the diagnosis.²

Classically, histology from the eschar shows signs of vasculitis and rickettsial microorganisms inside endothelial cells on electron microscopy.^2,10 More recent publications describe important necrotic changes within keratinocytes as well as an inflammatory infiltrate comprising antigen-presenting cells, monocytes, macrophages, and dendritic cells. Using high-resolution thin sections with confocal laser scanning microscopy and staining of specific monoclonal antibodies against 56 kDa type-specific surface antigens, the bacteria were found inside antigen-presenting cells, many of them located perivascularly or passing through the endothelium.¹¹

The causal agent in Asia is O tsutsugamushi, an obligate intracellular bacterium (genus Rickettsia). Orientia species are transmitted by larvae of trombiculid mites, commonly called chiggers. The reservoir is believed to be the same as with chiggers, in which some vertebrates become infected and trombiculid mites feed on them.¹² Recent studies of Chilean cases have revealed the presence of a novel Orientia species, Candidatus Orientia chiloensis and its vector, trombiculid mites from the Herpetacarus species, Quadraseta species, and Paratrombicula species genera.^13,14

A high seroprevalence of Orientia species in dogs was reported in the main cities of Chiloé Island. Rates were higher in rural settings and older dogs. Of 202 specimens, 21.3% were positive for IgG against Orientia species.¹⁵

In Chile, most cases of ST came from Chiloé Island; some reports of cases from continental Chilean regions have been published.⁶ Most cases have occurred in the context of activities that brought the patients in contact with plants and firewood in rural areas during the summer.^3-6

The diagnosis of ST is eminently clinical, based on the triad of fever, macular or papular rash, and an inoculation necrotic eschar. The diagnosis is supported by epidemiologic facts and fast recovery after treatment is initiated.¹⁶ Although the diagnosis can be established based on a quick recovery in endemic countries, in areas such as Chile where incidence and distribution are not completely known, it is better to confirm the diagnosis with laboratory tests without delaying treatment. Several testing options exist, including serologic techniques (immunofluorescence or enzyme-linked immunosorbent assay), culture, and detection of the genetic material of Orientia species by PCR. Usually, IgM titers initially are negative, and IgG testing requires paired samples (acute and convalescent) to demonstrate seroconversion and therefore acute infection.¹⁷ Because culture requires a highly specialized laboratory, it is not frequently used. Polymerase chain reaction is recognized as the best confirmation method due to its high sensitivity and because it remains positive for a few days after treatment has been initiated. The specimen of choice is the eschar because of its high bacterial load. The base of the scar and the buffy coat are useful specimens when the eschar is unavailable.^5,17-19

Due to potential complications of ST, empirical treatment with an antibiotic should be started based on clinical facts and never delayed because of diagnostic tests.¹⁸ Classically, ST is treated with a member of the tetracycline family, such as doxycycline, which provides a cure rate of 63% to 100% in ST.⁵

A 2017 systematic review of treatment options for this infection examined 11 studies from Southeast Asia, China, and South Korea (N=957).¹⁶ The review mainly compared doxycycline with azithromycin, chloramphenicol, and tetracycline. No significant difference in cure rate was noted in comparing doxycycline with any of the other 3 antibiotics; most of the studies examined were characterized by a moderate level of evidence. Regarding adverse effects, doxycycline showed a few more cases of gastrointestinal intolerance, and in 2 of 4 studies with chloramphenicol, patients presented with leukopenia.¹⁶ Several studies compared standard treatment (doxycycline) with rifampicin, telithromycin, erythromycin, and levofloxacin individually; similar cure rates were noted between doxycycline and each of those 4 agents.

Therapeutic failure in ST has been reported in several cases with the use of levofloxacin.²⁰ Evidence for this novel antibiotic is still insufficient. Further studies are needed before rifampicin, telithromycin, erythromycin, or levofloxacin can be considered as options.Scrub typhus usually resolves within a few weeks. Left untreated, the disease can cause complications such as pneumonia, meningoencephalitis, renal failure, and even multiorgan failure and death. Without treatment, mortality is variable. A 2015 systematic review of mortality from untreated ST showed, on average, mortality of 6% (range, 0%–70%).²¹ When ST is treated, mortality falls to 0% to 30%.²² Cases reported in Chile have neither been lethal nor presented with severe complications.^4,5

Scrub typhus is an infectious disease common in Asia, caused by O tsutsugamushi and transmitted by chiggers. It should be suspected when a febrile macular or papular rash and a tache noire appear. The diagnosis can be supported by laboratory findings, such as an elevated C-reactive protein level or a slight increase in the levels of hepatic transaminases, and response to treatment. The diagnosis is confirmed by serology or PCR of a specimen of the eschar. Empiric therapy with antibiotics is mandatory; doxycycline is the first option.

First described in Chile in 2011,² ST was seen in a patient in whom disease was suspected because of clinical characteristics, laboratory and histologic findings, absence of prior reporting in South America, and confirmation with PCR targeting the 16S ribosomal RNA Orientia gene from specimens of the eschar. By 2020, 60 cases have been confirmed in Chile, not all of them published; there are no other reported cases in South America.

When comparing the first case in Chile² with our case, we noted that both described classic clinical findings; however, the management approach and diagnostic challenges have evolved over time. Nowadays, ST is highly suspected, so it can be largely recognized and treated, which also provides better understanding of the nature of this disease in Chile. Because this infection is diagnosed mainly by characteristic cutaneous lesions, dermatologists should be aware of its epidemiology, clinical features, and transmission, and they should stay open to the possibility of this (until now) unusual diagnosis in South America.

Acknowledgments
The authors would like to thank the Chilean Rickettsia & Zoonosis Research Group (Thomas Weitzel, MD [Santiago, Chile]; Constanza Martínez-Valdebenito [Santiago, Chile]; and Gerardo Acosta-Jammet, DSc [Valdivia, Chile]), whose study in execution in the country allowed the detection of the case and confirmation by PCR. The authors also thank Juan Carlos Román, MD (Chiloé, Chile) who was part of the team that detected this case.

To the Editor:

Scrub typhus (ST) is an infection caused by Orientia tsutsugamushi (genus Rickettsia), which is transmitted by the larvae of trombiculid mites, commonly called chiggers. The disease mainly has been described in Asia in an area known as the Tsutsugamushi Triangle, delineated by Pakistan, eastern Russia, and northern Australia. Although this classic distribution remains, recent reports have documented 1 case in the Arabian Peninsula¹ and more than 16 cases in southern Chile.^2-4 The first case in Chile was published in 2011 from Chiloé Island.² To date, no other cases have been reported in the Americas.^1-6

We describe a new case of ST from Chiloé Island and compare it to the first case reported in Chile in 2011.² Both patients showed the typical clinical manifestation, but because ST has become an increasingly suspected disease in southern regions of Chile, new cases are now easily diagnosed. This infection is diagnosed mainly by skin lesions; therefore, dermatologists should be aware of this diagnosis when presented with a febrile rash.

A 67-year-old man from the city of Punta Arenas presented to the emergency department with a dark necrotic lesion on the right foot of 1 week’s duration. The patient later developed a generalized pruritic rash and fever. He also reported muscle pain, headache, cough, night sweats, and odynophagia. He reported recent travel to a rural area in the northern part of Chiloé Island, where he came into contact with firewood and participated in outdoor activities. He had no other relevant medical history.

Physical examination revealed a temperature of 38 °C and a macular rash, with some papules distributed mainly on the face, trunk, and proximal extremities (Figure 1). He had a necrotic eschar on the dorsum of the right foot, with an erythematous halo (tache noire)(Figure 2).

Scrub typhus is a high-impact disease in Asia, described mainly in an area known as the Tsutsugamushi Triangle. Recent reports show important epidemiologic changes in the distribution of the disease, with new published reports of cases outside this endemic area—1 in the Arabian peninsula¹ and more than 16 in southern Chile.^2-4

The disease begins with a painless, erythematous, and usually unnoticed papule at the site of the bite. After 48 to 72 hours, the papule changes to a necrotic form (tache noire), surrounded by a red halo that often is small, similar to a cigarette burn. This lesion is described in 20% to 90% of infected patients in different series.⁷ Two or 3 days later (1 to 3 weeks after exposure), high fever suddenly develops. Along with fever, a maculopapular rash distributed centrifugally develops, without compromise of the palms or soles. Patients frequently report headache and night sweating. Sometimes, ST is accompanied by muscle or joint pain, red eye, cough, and abdominal pain. Hearing loss and altered mental status less frequently have been reported.^5,8

Common laboratory tests can be of use in diagnosis. An elevated C-reactive protein level and a slight to moderate increase in hepatic transaminases should be expected. Thrombocytopenia, leukopenia, and elevation of the lactate dehydrogenase level less frequently are present.^5,9

Our case de1monstrated a typical presentation. The patient developed a febrile syndrome with a generalized rash and a tache noire–type eschar associated with muscle pain, headache, cough, night sweats, and odynophagia. Because of epidemiologic changes in the area, the familiar clinical findings, and laboratory confirmation, histologic studies were unnecessary. In cases in which the diagnosis is not evident, skin biopsy could be useful, as in the first case reported in Chile.²

In that first case, the patient initially was hospitalized because of a febrile syndrome; eventually, a necrotic eschar was noticed on his leg. He had been staying on Chiloé Island and reported being bitten by leeches on multiple occasions. Laboratory findings revealed only slightly raised levels of hepatic transaminases and alkaline phosphatase. After a more precise dermatologic evaluation, the eschar of a tache noire, combined with other clinical and laboratory findings, raised suspicion of ST. Because this entity had never been described in Chile, biopsy of the eschar was taken to consider other entities in the differential diagnosis. Biopsy showed necrotizing leukocytoclastic vasculitis in the dermis and subcutaneous tissue, perivascular inflammatory infiltrates comprising lymphocytes and macrophages, and rickettsial microorganisms inside endothelial cells under electron microscopic examination. The specimen was tested for the 16S ribosomal RNA Orientia gene; its presence confirmed the diagnosis.²

Classically, histology from the eschar shows signs of vasculitis and rickettsial microorganisms inside endothelial cells on electron microscopy.^2,10 More recent publications describe important necrotic changes within keratinocytes as well as an inflammatory infiltrate comprising antigen-presenting cells, monocytes, macrophages, and dendritic cells. Using high-resolution thin sections with confocal laser scanning microscopy and staining of specific monoclonal antibodies against 56 kDa type-specific surface antigens, the bacteria were found inside antigen-presenting cells, many of them located perivascularly or passing through the endothelium.¹¹

The causal agent in Asia is O tsutsugamushi, an obligate intracellular bacterium (genus Rickettsia). Orientia species are transmitted by larvae of trombiculid mites, commonly called chiggers. The reservoir is believed to be the same as with chiggers, in which some vertebrates become infected and trombiculid mites feed on them.¹² Recent studies of Chilean cases have revealed the presence of a novel Orientia species, Candidatus Orientia chiloensis and its vector, trombiculid mites from the Herpetacarus species, Quadraseta species, and Paratrombicula species genera.^13,14

A high seroprevalence of Orientia species in dogs was reported in the main cities of Chiloé Island. Rates were higher in rural settings and older dogs. Of 202 specimens, 21.3% were positive for IgG against Orientia species.¹⁵

In Chile, most cases of ST came from Chiloé Island; some reports of cases from continental Chilean regions have been published.⁶ Most cases have occurred in the context of activities that brought the patients in contact with plants and firewood in rural areas during the summer.^3-6

The diagnosis of ST is eminently clinical, based on the triad of fever, macular or papular rash, and an inoculation necrotic eschar. The diagnosis is supported by epidemiologic facts and fast recovery after treatment is initiated.¹⁶ Although the diagnosis can be established based on a quick recovery in endemic countries, in areas such as Chile where incidence and distribution are not completely known, it is better to confirm the diagnosis with laboratory tests without delaying treatment. Several testing options exist, including serologic techniques (immunofluorescence or enzyme-linked immunosorbent assay), culture, and detection of the genetic material of Orientia species by PCR. Usually, IgM titers initially are negative, and IgG testing requires paired samples (acute and convalescent) to demonstrate seroconversion and therefore acute infection.¹⁷ Because culture requires a highly specialized laboratory, it is not frequently used. Polymerase chain reaction is recognized as the best confirmation method due to its high sensitivity and because it remains positive for a few days after treatment has been initiated. The specimen of choice is the eschar because of its high bacterial load. The base of the scar and the buffy coat are useful specimens when the eschar is unavailable.^5,17-19

Due to potential complications of ST, empirical treatment with an antibiotic should be started based on clinical facts and never delayed because of diagnostic tests.¹⁸ Classically, ST is treated with a member of the tetracycline family, such as doxycycline, which provides a cure rate of 63% to 100% in ST.⁵

A 2017 systematic review of treatment options for this infection examined 11 studies from Southeast Asia, China, and South Korea (N=957).¹⁶ The review mainly compared doxycycline with azithromycin, chloramphenicol, and tetracycline. No significant difference in cure rate was noted in comparing doxycycline with any of the other 3 antibiotics; most of the studies examined were characterized by a moderate level of evidence. Regarding adverse effects, doxycycline showed a few more cases of gastrointestinal intolerance, and in 2 of 4 studies with chloramphenicol, patients presented with leukopenia.¹⁶ Several studies compared standard treatment (doxycycline) with rifampicin, telithromycin, erythromycin, and levofloxacin individually; similar cure rates were noted between doxycycline and each of those 4 agents.

Therapeutic failure in ST has been reported in several cases with the use of levofloxacin.²⁰ Evidence for this novel antibiotic is still insufficient. Further studies are needed before rifampicin, telithromycin, erythromycin, or levofloxacin can be considered as options.Scrub typhus usually resolves within a few weeks. Left untreated, the disease can cause complications such as pneumonia, meningoencephalitis, renal failure, and even multiorgan failure and death. Without treatment, mortality is variable. A 2015 systematic review of mortality from untreated ST showed, on average, mortality of 6% (range, 0%–70%).²¹ When ST is treated, mortality falls to 0% to 30%.²² Cases reported in Chile have neither been lethal nor presented with severe complications.^4,5

Scrub typhus is an infectious disease common in Asia, caused by O tsutsugamushi and transmitted by chiggers. It should be suspected when a febrile macular or papular rash and a tache noire appear. The diagnosis can be supported by laboratory findings, such as an elevated C-reactive protein level or a slight increase in the levels of hepatic transaminases, and response to treatment. The diagnosis is confirmed by serology or PCR of a specimen of the eschar. Empiric therapy with antibiotics is mandatory; doxycycline is the first option.

First described in Chile in 2011,² ST was seen in a patient in whom disease was suspected because of clinical characteristics, laboratory and histologic findings, absence of prior reporting in South America, and confirmation with PCR targeting the 16S ribosomal RNA Orientia gene from specimens of the eschar. By 2020, 60 cases have been confirmed in Chile, not all of them published; there are no other reported cases in South America.

When comparing the first case in Chile² with our case, we noted that both described classic clinical findings; however, the management approach and diagnostic challenges have evolved over time. Nowadays, ST is highly suspected, so it can be largely recognized and treated, which also provides better understanding of the nature of this disease in Chile. Because this infection is diagnosed mainly by characteristic cutaneous lesions, dermatologists should be aware of its epidemiology, clinical features, and transmission, and they should stay open to the possibility of this (until now) unusual diagnosis in South America.

Acknowledgments
The authors would like to thank the Chilean Rickettsia & Zoonosis Research Group (Thomas Weitzel, MD [Santiago, Chile]; Constanza Martínez-Valdebenito [Santiago, Chile]; and Gerardo Acosta-Jammet, DSc [Valdivia, Chile]), whose study in execution in the country allowed the detection of the case and confirmation by PCR. The authors also thank Juan Carlos Román, MD (Chiloé, Chile) who was part of the team that detected this case.