Case Letter

To the Editor:

A 63-year-old man presented with a prior diagnosis of severe psoriasis affecting the extremities, neck, face, and scalp of 1 year’s duration. He reported pain, itching, and swelling in the affected areas. He felt the rash was worst on the hands and feet, and pain made performing activities of daily living difficult. His treatment regimen at presentation included triamcinolone cream 0.1% and azathioprine 150 mg daily as prescribed by an outside dermatologist without any response. Physical examination revealed diffuse erythema with lichenification and thick, white, flaking scale on the arms and legs (Figure 1A), face, neck, palms, and soles with islands of sparing. Multiple salmon-colored, follicular-based papules topped with central hyperkeratosis were scattered on these same areas. The palms and soles had severe confluent keratoderma (Figure 2A). Histologic examination of a follicular-based papule showed foci of parakeratosis and hypergranulosis consistent with the patient’s clinical picture of pityriasis rubra pilaris (PRP).

Baseline laboratory tests at the time of PRP diagnosis revealed 20.8% eosinophils (reference range, 0%–7%) and an absolute eosinophil count of 2.17×10⁹/L (reference range, 0–0.7×10⁹/L). Laboratory test results from an outside dermatologist conducted 10 to 12 months prior to the current presentation showed 12% eosinophils with a white blood cell count of 8.9×10⁹/L (reference range, 4.5–11.0×10⁹/L) around the time of rash onset and before treatment with azathioprine, making a drug reaction an unlikely cause of the eosinophilia.

After consulting with the hematology department, a hypereosinophilia workup including erythrocyte sedimentation rate, lactate dehydrogenase, serum protein electrophoresis, urine protein electrophoresis, tryptase, double-stranded DNA antibody, human T-lymphotrophic virus I/II, stool ova, and parasites, as well as a Strongyloides antibody titer, were performed; all were within reference range. His antinuclear antibody level was mildly elevated at 1:160, but the patient had no clinical manifestations of lupus. Given this negative workup, the most likely explanation for the hypereosinophilia was a reactive process secondary to the extreme inflammatory state.

The patient was started on isotretinoin 40 mg daily in addition to urea cream 40% mixed with clobetasol ointment at least once daily to the extremities. Hydrocortisone ointment 2.5% and petrolatum-based ointment were applied to the face, and hydroxyzine was used as needed for pruritus. One month after initiating isotretinoin, erythema had decreased and a repeat complete blood cell count with differential showed a decrease of eosinophils to 14.7% and an absolute eosinophil count of 1.56×10⁹/L. After 2 months of therapy, the patient showed remarkable improvement. After 3.5 months of therapy, the keratoderma on the palms and soles was almost completely resolved, the follicular-based papules disappeared, and the patient had no areas of lichenification (Figures 1B and 2B). After 5 months of therapy, the patient experienced resolution of the PRP, except for residual facial erythema. His eosinophil count continued to trend downward during these 5 months, reaching 7.6% with an absolute eosinophil count of 0.93×10⁹/L. Three years after the initial onset of the rash and 2 years after completing isotretinoin, his eosinophil level was normal at 5.3% with an absolute eosinophil count of 0.7×10⁹/L.

We present a case of PRP and severe eosinophilia. We initially considered a second disease process to explain the extremely elevated eosinophil count; however, a negative eosinophilia workup and simultaneous resolution of these problems suggest that the eosinophilia was related to the severity of the PRP.

To the Editor:

A 63-year-old man presented with a prior diagnosis of severe psoriasis affecting the extremities, neck, face, and scalp of 1 year’s duration. He reported pain, itching, and swelling in the affected areas. He felt the rash was worst on the hands and feet, and pain made performing activities of daily living difficult. His treatment regimen at presentation included triamcinolone cream 0.1% and azathioprine 150 mg daily as prescribed by an outside dermatologist without any response. Physical examination revealed diffuse erythema with lichenification and thick, white, flaking scale on the arms and legs (Figure 1A), face, neck, palms, and soles with islands of sparing. Multiple salmon-colored, follicular-based papules topped with central hyperkeratosis were scattered on these same areas. The palms and soles had severe confluent keratoderma (Figure 2A). Histologic examination of a follicular-based papule showed foci of parakeratosis and hypergranulosis consistent with the patient’s clinical picture of pityriasis rubra pilaris (PRP).

Baseline laboratory tests at the time of PRP diagnosis revealed 20.8% eosinophils (reference range, 0%–7%) and an absolute eosinophil count of 2.17×10⁹/L (reference range, 0–0.7×10⁹/L). Laboratory test results from an outside dermatologist conducted 10 to 12 months prior to the current presentation showed 12% eosinophils with a white blood cell count of 8.9×10⁹/L (reference range, 4.5–11.0×10⁹/L) around the time of rash onset and before treatment with azathioprine, making a drug reaction an unlikely cause of the eosinophilia.

After consulting with the hematology department, a hypereosinophilia workup including erythrocyte sedimentation rate, lactate dehydrogenase, serum protein electrophoresis, urine protein electrophoresis, tryptase, double-stranded DNA antibody, human T-lymphotrophic virus I/II, stool ova, and parasites, as well as a Strongyloides antibody titer, were performed; all were within reference range. His antinuclear antibody level was mildly elevated at 1:160, but the patient had no clinical manifestations of lupus. Given this negative workup, the most likely explanation for the hypereosinophilia was a reactive process secondary to the extreme inflammatory state.

The patient was started on isotretinoin 40 mg daily in addition to urea cream 40% mixed with clobetasol ointment at least once daily to the extremities. Hydrocortisone ointment 2.5% and petrolatum-based ointment were applied to the face, and hydroxyzine was used as needed for pruritus. One month after initiating isotretinoin, erythema had decreased and a repeat complete blood cell count with differential showed a decrease of eosinophils to 14.7% and an absolute eosinophil count of 1.56×10⁹/L. After 2 months of therapy, the patient showed remarkable improvement. After 3.5 months of therapy, the keratoderma on the palms and soles was almost completely resolved, the follicular-based papules disappeared, and the patient had no areas of lichenification (Figures 1B and 2B). After 5 months of therapy, the patient experienced resolution of the PRP, except for residual facial erythema. His eosinophil count continued to trend downward during these 5 months, reaching 7.6% with an absolute eosinophil count of 0.93×10⁹/L. Three years after the initial onset of the rash and 2 years after completing isotretinoin, his eosinophil level was normal at 5.3% with an absolute eosinophil count of 0.7×10⁹/L.

We present a case of PRP and severe eosinophilia. We initially considered a second disease process to explain the extremely elevated eosinophil count; however, a negative eosinophilia workup and simultaneous resolution of these problems suggest that the eosinophilia was related to the severity of the PRP.

To the Editor:

A 63-year-old man presented with a prior diagnosis of severe psoriasis affecting the extremities, neck, face, and scalp of 1 year’s duration. He reported pain, itching, and swelling in the affected areas. He felt the rash was worst on the hands and feet, and pain made performing activities of daily living difficult. His treatment regimen at presentation included triamcinolone cream 0.1% and azathioprine 150 mg daily as prescribed by an outside dermatologist without any response. Physical examination revealed diffuse erythema with lichenification and thick, white, flaking scale on the arms and legs (Figure 1A), face, neck, palms, and soles with islands of sparing. Multiple salmon-colored, follicular-based papules topped with central hyperkeratosis were scattered on these same areas. The palms and soles had severe confluent keratoderma (Figure 2A). Histologic examination of a follicular-based papule showed foci of parakeratosis and hypergranulosis consistent with the patient’s clinical picture of pityriasis rubra pilaris (PRP).

Baseline laboratory tests at the time of PRP diagnosis revealed 20.8% eosinophils (reference range, 0%–7%) and an absolute eosinophil count of 2.17×10⁹/L (reference range, 0–0.7×10⁹/L). Laboratory test results from an outside dermatologist conducted 10 to 12 months prior to the current presentation showed 12% eosinophils with a white blood cell count of 8.9×10⁹/L (reference range, 4.5–11.0×10⁹/L) around the time of rash onset and before treatment with azathioprine, making a drug reaction an unlikely cause of the eosinophilia.

After consulting with the hematology department, a hypereosinophilia workup including erythrocyte sedimentation rate, lactate dehydrogenase, serum protein electrophoresis, urine protein electrophoresis, tryptase, double-stranded DNA antibody, human T-lymphotrophic virus I/II, stool ova, and parasites, as well as a Strongyloides antibody titer, were performed; all were within reference range. His antinuclear antibody level was mildly elevated at 1:160, but the patient had no clinical manifestations of lupus. Given this negative workup, the most likely explanation for the hypereosinophilia was a reactive process secondary to the extreme inflammatory state.

The patient was started on isotretinoin 40 mg daily in addition to urea cream 40% mixed with clobetasol ointment at least once daily to the extremities. Hydrocortisone ointment 2.5% and petrolatum-based ointment were applied to the face, and hydroxyzine was used as needed for pruritus. One month after initiating isotretinoin, erythema had decreased and a repeat complete blood cell count with differential showed a decrease of eosinophils to 14.7% and an absolute eosinophil count of 1.56×10⁹/L. After 2 months of therapy, the patient showed remarkable improvement. After 3.5 months of therapy, the keratoderma on the palms and soles was almost completely resolved, the follicular-based papules disappeared, and the patient had no areas of lichenification (Figures 1B and 2B). After 5 months of therapy, the patient experienced resolution of the PRP, except for residual facial erythema. His eosinophil count continued to trend downward during these 5 months, reaching 7.6% with an absolute eosinophil count of 0.93×10⁹/L. Three years after the initial onset of the rash and 2 years after completing isotretinoin, his eosinophil level was normal at 5.3% with an absolute eosinophil count of 0.7×10⁹/L.

We present a case of PRP and severe eosinophilia. We initially considered a second disease process to explain the extremely elevated eosinophil count; however, a negative eosinophilia workup and simultaneous resolution of these problems suggest that the eosinophilia was related to the severity of the PRP.

To the Editor:

We present a case of Mycobacterium chelonae-abscessus cutaneous infection in a sporotrichoid pattern, a rare presentation most often found in immunocompromised patients. A 34-year-old man with lupus nephritis who was taking oral prednisone, mycophenolate mofetil, and hydroxychloroquine presented with multiple erythematous fluctuant nodules and plaques on the left volar forearm in a sporotrichoid pattern of 3 months’ duration (Figure, A). He denied recent travel, exposure to fish or fish tanks, and penetrating wounds. Punch biopsy showed granulomatous inflammation and scarring with negative tissue cultures. Repeat biopsies and cultures were obtained when the lesions increased in number over 2 months.

Final biopsy showed upper dermal granulomatous inflammation with karyorrhectic debris, suggesting infection, and acid-fast bacilli. Culture grew M chelonae-abscessus on Löwenstein-Jensen agar at 37°C and blood culture media from which the complex was identified using high-performance liquid chromatography. Empiric therapy with renal dosing based on the Infectious Diseases Society of America statement of susceptibilities¹ was initiated with clarithromycin, doxycycline, and ciprofloxacin for 4 months. Furthermore, the prednisone dose was tapered to 7.5 mg daily. Two months later, the lesions regressed and ciprofloxacin was discontinued (Figure, B).

The sporotrichoid spread of nodules suggests infection with mycobacteria, Sporothrix schenckii, Leishmania, Francisella tularensis, or Nocardia. Most cultures for nontuberculous mycobacteria will grow on Löwenstein-Jensen agar between 28°C and 37°C. Runyon rapidly growing (group IV) mycobacteria are defined by their ubiquitous presence in the environment and ability to develop colonies in 7 days.² Cutaneous infections are increasing in prevalence, as reported in a retrospective study spanning nearly 30 years.³ The presentation is variable but often includes the distal extremities and usually is a nodule, ulcer, or abscess at a single site; a sporotrichoid pattern is more rare. Preceding skin trauma is the major risk factor for immunocompetent hosts, and the infection can spontaneously resolve in 8 to 12 months.¹ In contrast, immunosuppressed patients may have no known source of infection and often have a progressive course with an increasing number of lesions and increased time until clearance.⁴

It is difficult to differentiate M chelonae and M abscessus based on growth characteristics, and they share the same 16S ribosomal RNA sequence commonly used to differentiate other mycobacterial species.²Mycobacterium abscessus can be more difficult to treat, thus distinction via polymerase chain reaction of the heat-shock protein 65 gene, hsp65, can be valuable in cases recalcitrant to initial therapy.¹

The likelihood of M chelonae and M abscessus isolates to be initially sensitive to clarithromycin is 100%,¹ and this antibiotic remains the cornerstone of therapy. A clinical trial of treatments for M chelonae-abscessus found that clarithromycin monotherapy can be successful or complicated by resistance⁵; therefore, multidrug therapy is recommended. The antibiotic regimen for our patient was chosen to limit renal toxicity.

In summary, we report a case of M chelonae-abscessus cutaneous infection in a sporotrichoid pattern in a patient with lupus nephritis on immunosuppressive drugs. As the incidence of rapidly growing mycobacterial cutaneous infections rises, dermatologists must be aware of this pattern of infection.

To the Editor:

We present a case of Mycobacterium chelonae-abscessus cutaneous infection in a sporotrichoid pattern, a rare presentation most often found in immunocompromised patients. A 34-year-old man with lupus nephritis who was taking oral prednisone, mycophenolate mofetil, and hydroxychloroquine presented with multiple erythematous fluctuant nodules and plaques on the left volar forearm in a sporotrichoid pattern of 3 months’ duration (Figure, A). He denied recent travel, exposure to fish or fish tanks, and penetrating wounds. Punch biopsy showed granulomatous inflammation and scarring with negative tissue cultures. Repeat biopsies and cultures were obtained when the lesions increased in number over 2 months.

Final biopsy showed upper dermal granulomatous inflammation with karyorrhectic debris, suggesting infection, and acid-fast bacilli. Culture grew M chelonae-abscessus on Löwenstein-Jensen agar at 37°C and blood culture media from which the complex was identified using high-performance liquid chromatography. Empiric therapy with renal dosing based on the Infectious Diseases Society of America statement of susceptibilities¹ was initiated with clarithromycin, doxycycline, and ciprofloxacin for 4 months. Furthermore, the prednisone dose was tapered to 7.5 mg daily. Two months later, the lesions regressed and ciprofloxacin was discontinued (Figure, B).

The sporotrichoid spread of nodules suggests infection with mycobacteria, Sporothrix schenckii, Leishmania, Francisella tularensis, or Nocardia. Most cultures for nontuberculous mycobacteria will grow on Löwenstein-Jensen agar between 28°C and 37°C. Runyon rapidly growing (group IV) mycobacteria are defined by their ubiquitous presence in the environment and ability to develop colonies in 7 days.² Cutaneous infections are increasing in prevalence, as reported in a retrospective study spanning nearly 30 years.³ The presentation is variable but often includes the distal extremities and usually is a nodule, ulcer, or abscess at a single site; a sporotrichoid pattern is more rare. Preceding skin trauma is the major risk factor for immunocompetent hosts, and the infection can spontaneously resolve in 8 to 12 months.¹ In contrast, immunosuppressed patients may have no known source of infection and often have a progressive course with an increasing number of lesions and increased time until clearance.⁴

It is difficult to differentiate M chelonae and M abscessus based on growth characteristics, and they share the same 16S ribosomal RNA sequence commonly used to differentiate other mycobacterial species.²Mycobacterium abscessus can be more difficult to treat, thus distinction via polymerase chain reaction of the heat-shock protein 65 gene, hsp65, can be valuable in cases recalcitrant to initial therapy.¹

The likelihood of M chelonae and M abscessus isolates to be initially sensitive to clarithromycin is 100%,¹ and this antibiotic remains the cornerstone of therapy. A clinical trial of treatments for M chelonae-abscessus found that clarithromycin monotherapy can be successful or complicated by resistance⁵; therefore, multidrug therapy is recommended. The antibiotic regimen for our patient was chosen to limit renal toxicity.

In summary, we report a case of M chelonae-abscessus cutaneous infection in a sporotrichoid pattern in a patient with lupus nephritis on immunosuppressive drugs. As the incidence of rapidly growing mycobacterial cutaneous infections rises, dermatologists must be aware of this pattern of infection.

To the Editor:

We present a case of Mycobacterium chelonae-abscessus cutaneous infection in a sporotrichoid pattern, a rare presentation most often found in immunocompromised patients. A 34-year-old man with lupus nephritis who was taking oral prednisone, mycophenolate mofetil, and hydroxychloroquine presented with multiple erythematous fluctuant nodules and plaques on the left volar forearm in a sporotrichoid pattern of 3 months’ duration (Figure, A). He denied recent travel, exposure to fish or fish tanks, and penetrating wounds. Punch biopsy showed granulomatous inflammation and scarring with negative tissue cultures. Repeat biopsies and cultures were obtained when the lesions increased in number over 2 months.

Final biopsy showed upper dermal granulomatous inflammation with karyorrhectic debris, suggesting infection, and acid-fast bacilli. Culture grew M chelonae-abscessus on Löwenstein-Jensen agar at 37°C and blood culture media from which the complex was identified using high-performance liquid chromatography. Empiric therapy with renal dosing based on the Infectious Diseases Society of America statement of susceptibilities¹ was initiated with clarithromycin, doxycycline, and ciprofloxacin for 4 months. Furthermore, the prednisone dose was tapered to 7.5 mg daily. Two months later, the lesions regressed and ciprofloxacin was discontinued (Figure, B).

The sporotrichoid spread of nodules suggests infection with mycobacteria, Sporothrix schenckii, Leishmania, Francisella tularensis, or Nocardia. Most cultures for nontuberculous mycobacteria will grow on Löwenstein-Jensen agar between 28°C and 37°C. Runyon rapidly growing (group IV) mycobacteria are defined by their ubiquitous presence in the environment and ability to develop colonies in 7 days.² Cutaneous infections are increasing in prevalence, as reported in a retrospective study spanning nearly 30 years.³ The presentation is variable but often includes the distal extremities and usually is a nodule, ulcer, or abscess at a single site; a sporotrichoid pattern is more rare. Preceding skin trauma is the major risk factor for immunocompetent hosts, and the infection can spontaneously resolve in 8 to 12 months.¹ In contrast, immunosuppressed patients may have no known source of infection and often have a progressive course with an increasing number of lesions and increased time until clearance.⁴

It is difficult to differentiate M chelonae and M abscessus based on growth characteristics, and they share the same 16S ribosomal RNA sequence commonly used to differentiate other mycobacterial species.²Mycobacterium abscessus can be more difficult to treat, thus distinction via polymerase chain reaction of the heat-shock protein 65 gene, hsp65, can be valuable in cases recalcitrant to initial therapy.¹

The likelihood of M chelonae and M abscessus isolates to be initially sensitive to clarithromycin is 100%,¹ and this antibiotic remains the cornerstone of therapy. A clinical trial of treatments for M chelonae-abscessus found that clarithromycin monotherapy can be successful or complicated by resistance⁵; therefore, multidrug therapy is recommended. The antibiotic regimen for our patient was chosen to limit renal toxicity.

In summary, we report a case of M chelonae-abscessus cutaneous infection in a sporotrichoid pattern in a patient with lupus nephritis on immunosuppressive drugs. As the incidence of rapidly growing mycobacterial cutaneous infections rises, dermatologists must be aware of this pattern of infection.

To the Editor:

A 22-year-old obese man with untreated mild asthma diagnosed in childhood presented to the emergency department with cheilitis (Figure 1); conjunctivitis; and painful desquamation of the oral mucosa, penis (Figure 2), and perirectal area (Figure 3). Physical examination was notable for palpebral conjunctiva; mucosal involvement with stomatitis (Figure 1B); and isolated 0.5- to 2-cm erosions and ulcerations with positive Nikolsky sign of the scrotum (Figure 2), trunk, back, and arms and legs. Some areas had evidence of hemorrhagic crust, flaccid bullae, and denudation. Few scant targetoid lesions and dusky red macules on the trunk, face, palms, and soles also were present.

One week prior to presentation he had an episode of diarrhea and dyspnea with symptoms of mild heat stroke after working outdoors, and he self-treated with ibuprofen, which he had taken intermittently for years. He was subsequently seen at an outpatient clinic and was prescribed an albuterol inhaler for previously untreated childhood asthma. The patient stated that he inhaled 2 puffs every 6 hours for a total of 3 treatments. Shortly after the last dose, he noticed a tingling sensation of the oral mucosa that developed into a painful 2-cm bullous ulcer. Over the next 3 days, he developed several more oral ulcers and erosions. Three days before admission he developed dysuria and tense bullae at the glans penis. After admission, he developed cheilitis, conjunctivitis, dysuria, odynophagia, and dysphagia to solids. One day after admission, the patient had the onset of systemic symptoms, including cough with worsening dyspnea, fever, chills, hemoptysis, epistaxis, nausea, diarrhea, loss of appetite, joint pain, and myalgia. Review of systems was otherwise negative. A radiograph was performed at admission and was notable for mild atelectasis but was otherwise normal. The chest radiograph was negative for signs of perihilar lymphadenopathy, pleural effusion, pneumothorax, or lobar infiltrates suggestive of bacterial pneumonia. It also did not show signs of patchy opacities or air bronchograms suggestive of an interstitial pneumonia. On admission, he was started on acyclovir, fluconazole, methylprednisolone, nystatin, pantoprazole, acetaminophen, topical bacitracin, oxycodone, and topical silver nitrate.

At the time of admission our patient was afebrile with a normal heart rate, blood pressure, and respiratory rate. However, he was hypoxic, with a pulse oximetry of 86% on room air and 94% on 40% fraction of inspired oxygen. Complete blood cell count, electrolytes, and liver function tests were all within reference range. Urinalysis revealed evidence of scant red blood cells without pyuria, and the erythrocyte sedimentation rate and creatine kinase level were both elevated. Two blood cultures; sputum cultures; and polymerase chain reaction for Mycoplasma pneumoniae, herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus were negative. Human immunodeficiency virus panel, antinuclear antibody screen, and hepatitis B and C panels were all negative. Four punch biopsies were obtained showing full-thickness epidermal necrosis with neutrophils, few dyskeratotic cells, and sparse inflammatory infiltrate compatible with Stevens-Johnson syndrome (SJS).

After hospital admission, the patient’s mucosal desquamation progressively improved. By day 3, he required minimal supplemental oxygen with resolution of bowel symptoms and improved mucosal and skin findings. He was discharged on day 4 with supplemental oxygen and a 7-day course of prednisone, fluconazole, liquid oxycodone, pantoprazole, and acetaminophen. He showed continued improvement at a follow-up outpatient visit 2 days following discharge.

Stevens-Johnson syndrome is a rare severe drug reaction characterized by high fevers, mucosal erosions, tenderness, and skin detachment approximately 1 to 3 weeks after an inciting event.^1,2 Although SJS has been linked to infections and less commonly to immunizations, in more than 80% of cases, SJS is strongly associated with a recent medication change.³ The classes of drugs that have been implicated in SJS most commonly include antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs.⁴ Stevens-Johnson syndrome from drug reactions is not uncommon; however, SJS secondary to isolated albuterol use is rare.

Although it is presumed that albuterol was the key inciting factor in our patient’s case of SJS, it also is recognized that mucosal SJS can be associated with M pneumoniae infection. For this reason, we performed polymerase chain reaction for M pneumoniae as well as a chest radiograph to rule out this possibility. In addition, our patient had denied prolonged respiratory symptoms suggestive of a mycoplasma pneumonia infection, such as a prodrome of cough, myalgia, headache, sore throat, or fever. A report of 8 patients with documented SJS and M pneumoniae as well as a review of the literature also demonstrated a mean of 10 days of prodromal symptoms prior to the onset of mucosal lesions and/or a rash.⁵ However, mucosal SJS associated with mycoplasma pneumonia is an important clinical entity that should not be forgotten during the workup of a young patient with mucosal lesions or rash suggestive of SJS.

The exact etiology and mechanism of drug-induced SJS is not well understood at this time; however, evidence suggests that SJS is strongly linked to the host’s inability to detoxify drug metabolites.^6,7 It has been postulated that SJS occurs secondary to a cell-mediated immune response, which activates cytotoxic T lymphocytes and subsequently results in keratinocyte apoptosis. Keratinocyte apoptosis occurs via the CD95-CD95 death receptor and soluble or membrane-bound ligand interaction.^3,8,9 Stevens-Johnson syndrome is thought to occur from an interaction involving an HLA antigen–restricted presentation of drug metabolites to cytotoxic T cells, which can be further supported by evidence of strong genetic associations with HLA antigen alleles B15.02 and B58.01 in the cases of carbamazepine- and allopurinol-induced SJS, respectively.^6,7 However, the genetic associations of specific HLA antigen alleles and polymorphisms with SJS and other cutaneous reactions is thought to be drug specific and HLA antigen subtype specific.⁷ Therefore, it is difficult to determine or correlate the clinical outcomes and manifestations of drug reactions in individualized patients. The precise mechanism of antigenicity of albuterol in initiating this cascade has not yet been determined. However, these investigations provide strong evidence for a correlation between specific HLA antigen haplotypes and occurrence of drug antigenicity resulting in SJS and other cutaneous reactions in susceptible patient populations.

Although the specific molecular pathway and etiology of SJS is not well delineated, pathology in combination with clinical correlation allows for diagnosis. Early-stage biopsies in SJS typically show apoptotic keratinocytes throughout the epidermis. Late-stage biopsies exhibit subepidermal blisters and full-thickness epidermal necrosis.¹ Histopathology was performed on 4-mm punch biopsies of the chest and back and demonstrated full-thickness epidermal necrosis with neutrophils and a few dyskeratotic cells, likely representing a late stage of epidermal involvement. Given the predominance of neutrophils, other diagnostic considerations based solely on the biopsy results included contact dermatitis or phototoxic dermatitis. The remaining inflammatory infiltrate was sparse. Immunofluorescence was pan-negative.

This report illustrates a rare case of SJS from isolated albuterol use. This adverse drug reaction has not been well reported in the literature and may be an important consideration in the management of a patient with asthma.

To the Editor:

A 22-year-old obese man with untreated mild asthma diagnosed in childhood presented to the emergency department with cheilitis (Figure 1); conjunctivitis; and painful desquamation of the oral mucosa, penis (Figure 2), and perirectal area (Figure 3). Physical examination was notable for palpebral conjunctiva; mucosal involvement with stomatitis (Figure 1B); and isolated 0.5- to 2-cm erosions and ulcerations with positive Nikolsky sign of the scrotum (Figure 2), trunk, back, and arms and legs. Some areas had evidence of hemorrhagic crust, flaccid bullae, and denudation. Few scant targetoid lesions and dusky red macules on the trunk, face, palms, and soles also were present.

One week prior to presentation he had an episode of diarrhea and dyspnea with symptoms of mild heat stroke after working outdoors, and he self-treated with ibuprofen, which he had taken intermittently for years. He was subsequently seen at an outpatient clinic and was prescribed an albuterol inhaler for previously untreated childhood asthma. The patient stated that he inhaled 2 puffs every 6 hours for a total of 3 treatments. Shortly after the last dose, he noticed a tingling sensation of the oral mucosa that developed into a painful 2-cm bullous ulcer. Over the next 3 days, he developed several more oral ulcers and erosions. Three days before admission he developed dysuria and tense bullae at the glans penis. After admission, he developed cheilitis, conjunctivitis, dysuria, odynophagia, and dysphagia to solids. One day after admission, the patient had the onset of systemic symptoms, including cough with worsening dyspnea, fever, chills, hemoptysis, epistaxis, nausea, diarrhea, loss of appetite, joint pain, and myalgia. Review of systems was otherwise negative. A radiograph was performed at admission and was notable for mild atelectasis but was otherwise normal. The chest radiograph was negative for signs of perihilar lymphadenopathy, pleural effusion, pneumothorax, or lobar infiltrates suggestive of bacterial pneumonia. It also did not show signs of patchy opacities or air bronchograms suggestive of an interstitial pneumonia. On admission, he was started on acyclovir, fluconazole, methylprednisolone, nystatin, pantoprazole, acetaminophen, topical bacitracin, oxycodone, and topical silver nitrate.

At the time of admission our patient was afebrile with a normal heart rate, blood pressure, and respiratory rate. However, he was hypoxic, with a pulse oximetry of 86% on room air and 94% on 40% fraction of inspired oxygen. Complete blood cell count, electrolytes, and liver function tests were all within reference range. Urinalysis revealed evidence of scant red blood cells without pyuria, and the erythrocyte sedimentation rate and creatine kinase level were both elevated. Two blood cultures; sputum cultures; and polymerase chain reaction for Mycoplasma pneumoniae, herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus were negative. Human immunodeficiency virus panel, antinuclear antibody screen, and hepatitis B and C panels were all negative. Four punch biopsies were obtained showing full-thickness epidermal necrosis with neutrophils, few dyskeratotic cells, and sparse inflammatory infiltrate compatible with Stevens-Johnson syndrome (SJS).

After hospital admission, the patient’s mucosal desquamation progressively improved. By day 3, he required minimal supplemental oxygen with resolution of bowel symptoms and improved mucosal and skin findings. He was discharged on day 4 with supplemental oxygen and a 7-day course of prednisone, fluconazole, liquid oxycodone, pantoprazole, and acetaminophen. He showed continued improvement at a follow-up outpatient visit 2 days following discharge.

Stevens-Johnson syndrome is a rare severe drug reaction characterized by high fevers, mucosal erosions, tenderness, and skin detachment approximately 1 to 3 weeks after an inciting event.^1,2 Although SJS has been linked to infections and less commonly to immunizations, in more than 80% of cases, SJS is strongly associated with a recent medication change.³ The classes of drugs that have been implicated in SJS most commonly include antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs.⁴ Stevens-Johnson syndrome from drug reactions is not uncommon; however, SJS secondary to isolated albuterol use is rare.

Although it is presumed that albuterol was the key inciting factor in our patient’s case of SJS, it also is recognized that mucosal SJS can be associated with M pneumoniae infection. For this reason, we performed polymerase chain reaction for M pneumoniae as well as a chest radiograph to rule out this possibility. In addition, our patient had denied prolonged respiratory symptoms suggestive of a mycoplasma pneumonia infection, such as a prodrome of cough, myalgia, headache, sore throat, or fever. A report of 8 patients with documented SJS and M pneumoniae as well as a review of the literature also demonstrated a mean of 10 days of prodromal symptoms prior to the onset of mucosal lesions and/or a rash.⁵ However, mucosal SJS associated with mycoplasma pneumonia is an important clinical entity that should not be forgotten during the workup of a young patient with mucosal lesions or rash suggestive of SJS.

The exact etiology and mechanism of drug-induced SJS is not well understood at this time; however, evidence suggests that SJS is strongly linked to the host’s inability to detoxify drug metabolites.^6,7 It has been postulated that SJS occurs secondary to a cell-mediated immune response, which activates cytotoxic T lymphocytes and subsequently results in keratinocyte apoptosis. Keratinocyte apoptosis occurs via the CD95-CD95 death receptor and soluble or membrane-bound ligand interaction.^3,8,9 Stevens-Johnson syndrome is thought to occur from an interaction involving an HLA antigen–restricted presentation of drug metabolites to cytotoxic T cells, which can be further supported by evidence of strong genetic associations with HLA antigen alleles B15.02 and B58.01 in the cases of carbamazepine- and allopurinol-induced SJS, respectively.^6,7 However, the genetic associations of specific HLA antigen alleles and polymorphisms with SJS and other cutaneous reactions is thought to be drug specific and HLA antigen subtype specific.⁷ Therefore, it is difficult to determine or correlate the clinical outcomes and manifestations of drug reactions in individualized patients. The precise mechanism of antigenicity of albuterol in initiating this cascade has not yet been determined. However, these investigations provide strong evidence for a correlation between specific HLA antigen haplotypes and occurrence of drug antigenicity resulting in SJS and other cutaneous reactions in susceptible patient populations.

Although the specific molecular pathway and etiology of SJS is not well delineated, pathology in combination with clinical correlation allows for diagnosis. Early-stage biopsies in SJS typically show apoptotic keratinocytes throughout the epidermis. Late-stage biopsies exhibit subepidermal blisters and full-thickness epidermal necrosis.¹ Histopathology was performed on 4-mm punch biopsies of the chest and back and demonstrated full-thickness epidermal necrosis with neutrophils and a few dyskeratotic cells, likely representing a late stage of epidermal involvement. Given the predominance of neutrophils, other diagnostic considerations based solely on the biopsy results included contact dermatitis or phototoxic dermatitis. The remaining inflammatory infiltrate was sparse. Immunofluorescence was pan-negative.

This report illustrates a rare case of SJS from isolated albuterol use. This adverse drug reaction has not been well reported in the literature and may be an important consideration in the management of a patient with asthma.

To the Editor:

A 22-year-old obese man with untreated mild asthma diagnosed in childhood presented to the emergency department with cheilitis (Figure 1); conjunctivitis; and painful desquamation of the oral mucosa, penis (Figure 2), and perirectal area (Figure 3). Physical examination was notable for palpebral conjunctiva; mucosal involvement with stomatitis (Figure 1B); and isolated 0.5- to 2-cm erosions and ulcerations with positive Nikolsky sign of the scrotum (Figure 2), trunk, back, and arms and legs. Some areas had evidence of hemorrhagic crust, flaccid bullae, and denudation. Few scant targetoid lesions and dusky red macules on the trunk, face, palms, and soles also were present.

One week prior to presentation he had an episode of diarrhea and dyspnea with symptoms of mild heat stroke after working outdoors, and he self-treated with ibuprofen, which he had taken intermittently for years. He was subsequently seen at an outpatient clinic and was prescribed an albuterol inhaler for previously untreated childhood asthma. The patient stated that he inhaled 2 puffs every 6 hours for a total of 3 treatments. Shortly after the last dose, he noticed a tingling sensation of the oral mucosa that developed into a painful 2-cm bullous ulcer. Over the next 3 days, he developed several more oral ulcers and erosions. Three days before admission he developed dysuria and tense bullae at the glans penis. After admission, he developed cheilitis, conjunctivitis, dysuria, odynophagia, and dysphagia to solids. One day after admission, the patient had the onset of systemic symptoms, including cough with worsening dyspnea, fever, chills, hemoptysis, epistaxis, nausea, diarrhea, loss of appetite, joint pain, and myalgia. Review of systems was otherwise negative. A radiograph was performed at admission and was notable for mild atelectasis but was otherwise normal. The chest radiograph was negative for signs of perihilar lymphadenopathy, pleural effusion, pneumothorax, or lobar infiltrates suggestive of bacterial pneumonia. It also did not show signs of patchy opacities or air bronchograms suggestive of an interstitial pneumonia. On admission, he was started on acyclovir, fluconazole, methylprednisolone, nystatin, pantoprazole, acetaminophen, topical bacitracin, oxycodone, and topical silver nitrate.

At the time of admission our patient was afebrile with a normal heart rate, blood pressure, and respiratory rate. However, he was hypoxic, with a pulse oximetry of 86% on room air and 94% on 40% fraction of inspired oxygen. Complete blood cell count, electrolytes, and liver function tests were all within reference range. Urinalysis revealed evidence of scant red blood cells without pyuria, and the erythrocyte sedimentation rate and creatine kinase level were both elevated. Two blood cultures; sputum cultures; and polymerase chain reaction for Mycoplasma pneumoniae, herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus were negative. Human immunodeficiency virus panel, antinuclear antibody screen, and hepatitis B and C panels were all negative. Four punch biopsies were obtained showing full-thickness epidermal necrosis with neutrophils, few dyskeratotic cells, and sparse inflammatory infiltrate compatible with Stevens-Johnson syndrome (SJS).

After hospital admission, the patient’s mucosal desquamation progressively improved. By day 3, he required minimal supplemental oxygen with resolution of bowel symptoms and improved mucosal and skin findings. He was discharged on day 4 with supplemental oxygen and a 7-day course of prednisone, fluconazole, liquid oxycodone, pantoprazole, and acetaminophen. He showed continued improvement at a follow-up outpatient visit 2 days following discharge.

Stevens-Johnson syndrome is a rare severe drug reaction characterized by high fevers, mucosal erosions, tenderness, and skin detachment approximately 1 to 3 weeks after an inciting event.^1,2 Although SJS has been linked to infections and less commonly to immunizations, in more than 80% of cases, SJS is strongly associated with a recent medication change.³ The classes of drugs that have been implicated in SJS most commonly include antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs.⁴ Stevens-Johnson syndrome from drug reactions is not uncommon; however, SJS secondary to isolated albuterol use is rare.

Although it is presumed that albuterol was the key inciting factor in our patient’s case of SJS, it also is recognized that mucosal SJS can be associated with M pneumoniae infection. For this reason, we performed polymerase chain reaction for M pneumoniae as well as a chest radiograph to rule out this possibility. In addition, our patient had denied prolonged respiratory symptoms suggestive of a mycoplasma pneumonia infection, such as a prodrome of cough, myalgia, headache, sore throat, or fever. A report of 8 patients with documented SJS and M pneumoniae as well as a review of the literature also demonstrated a mean of 10 days of prodromal symptoms prior to the onset of mucosal lesions and/or a rash.⁵ However, mucosal SJS associated with mycoplasma pneumonia is an important clinical entity that should not be forgotten during the workup of a young patient with mucosal lesions or rash suggestive of SJS.

The exact etiology and mechanism of drug-induced SJS is not well understood at this time; however, evidence suggests that SJS is strongly linked to the host’s inability to detoxify drug metabolites.^6,7 It has been postulated that SJS occurs secondary to a cell-mediated immune response, which activates cytotoxic T lymphocytes and subsequently results in keratinocyte apoptosis. Keratinocyte apoptosis occurs via the CD95-CD95 death receptor and soluble or membrane-bound ligand interaction.^3,8,9 Stevens-Johnson syndrome is thought to occur from an interaction involving an HLA antigen–restricted presentation of drug metabolites to cytotoxic T cells, which can be further supported by evidence of strong genetic associations with HLA antigen alleles B15.02 and B58.01 in the cases of carbamazepine- and allopurinol-induced SJS, respectively.^6,7 However, the genetic associations of specific HLA antigen alleles and polymorphisms with SJS and other cutaneous reactions is thought to be drug specific and HLA antigen subtype specific.⁷ Therefore, it is difficult to determine or correlate the clinical outcomes and manifestations of drug reactions in individualized patients. The precise mechanism of antigenicity of albuterol in initiating this cascade has not yet been determined. However, these investigations provide strong evidence for a correlation between specific HLA antigen haplotypes and occurrence of drug antigenicity resulting in SJS and other cutaneous reactions in susceptible patient populations.

Although the specific molecular pathway and etiology of SJS is not well delineated, pathology in combination with clinical correlation allows for diagnosis. Early-stage biopsies in SJS typically show apoptotic keratinocytes throughout the epidermis. Late-stage biopsies exhibit subepidermal blisters and full-thickness epidermal necrosis.¹ Histopathology was performed on 4-mm punch biopsies of the chest and back and demonstrated full-thickness epidermal necrosis with neutrophils and a few dyskeratotic cells, likely representing a late stage of epidermal involvement. Given the predominance of neutrophils, other diagnostic considerations based solely on the biopsy results included contact dermatitis or phototoxic dermatitis. The remaining inflammatory infiltrate was sparse. Immunofluorescence was pan-negative.

This report illustrates a rare case of SJS from isolated albuterol use. This adverse drug reaction has not been well reported in the literature and may be an important consideration in the management of a patient with asthma.

To the Editor:

Erythema ab igne (EAI) is a reticular erythematous hyperpigmentation of skin repeatedly exposed to moderate heat.¹ It usually is asymptomatic, though some patients report itching or burning at the site.² Historically caused by exposure to coal stoves or open fires, EAI has become increasingly common among individuals using space heaters, heating pads, or laptop computers near bare skin.^2,3 Although EAI itself is benign and usually resolves with the removal of the exposure, it remains of clinical importance because of its association with underlying chronic disease, as chronic pain often is managed with frequent heating pad or hot water bottle use.² Additionally, accurate diagnosis is important given the future risk for malignancy, as chronic changes of EAI have been reported to lead to squamous cell carcinoma or rarely Merkel cell carcinoma.² Erythema ab igne is not traditionally associated with the formation of bullae; however, we present a case of bullous EAI that we believe highlights the importance of including this condition in the differential diagnosis of bullous disorders.

A 55-year-old man was admitted for presumed cellulitis of the bilateral legs. The patient had developed hyperpigmented discoloration of the medial surface of both legs with subsequent formation of tense bullae over the last 2 months. The dermatology department was consulted, as there was concern for bullous pemphigoid. The patient’s medical history was notable for hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, and hepatitis C virus with cirrhosis. The patient denied pruritus, pain, or known exposure of the legs to potential irritants prior to developing the lesions; however, with additional questioning he did report frequently sitting in front of a space heater with bare legs. Physical examination revealed multiple areas of reticulated erythematous hyperpigmentation with several overlying bullae (Figure 1). Many of the bullae were unroofed with full-thickness ulceration. Biopsies were taken for hematoxylin and eosin staining (Figure 2) and direct immunofluorescence.

Basic hematologic and metabolic laboratory test results as well as blood cultures were negative. Wound culture was positive for methicillin-resistant Staphylococcus aureus. Histologic examination showed interface dermatitis with subepidermal vesicle (Figure 2). Scattered necrotic keratinocytes were present in the adjacent epidermis, and focal subtle vacuolar alteration of the dermoepidermal junction was seen (Figure 3). Sparse perivascular mononuclear cells and scattered melanophages were present in the dermis. Direct immunofluorescence showed no diagnostic immunopathologic abnormality. Focal weak nonspecific vascular positivity for IgG and C3 was seen, but IgA and IgM were negative. Although not specific, these changes were compatible with EAI in the clinical context provided. The diagnosis of bullous EAI with superimposed staphylococcal infection was made.

Although rare, there have been reports of a bullous variant of EAI. Flanagan et al⁴ described 3 cases of bullous EAI with histopathology similar to our case. All 3 biopsies showed subepidermal separation with a mild perivascular dermal lymphocytic infiltrate. Direct immunofluorescence was negative in 2 cases but showed nonspecific weak patchy deposition of IgM along the dermoepidermal junction.⁴ Although our case was negative for IgM, there was a similar weak nonspecific distribution of IgG. Kokturk et al⁵ described a case of bullous EAI in a man with repeated exposure to a space heater. The lesions showed subepidermal separation of the epidermis; increased elastic fibers; dilated dermal capillaries; melanophages in the upper dermis; and a mild, superficial, perivascular-lymphocytic infiltrate. Direct immunofluorescence showed no immune deposits.⁵ Several earlier cases of bullae associated with EAI have been reported in the literature but were thought to be bullous lichen planus superimposed on EAI.⁶ Our case, which exhibited similar historical, physical, and histopathologic findings, strengthens the argument for a defined bullous variant of EAI.

To the Editor:

Erythema ab igne (EAI) is a reticular erythematous hyperpigmentation of skin repeatedly exposed to moderate heat.¹ It usually is asymptomatic, though some patients report itching or burning at the site.² Historically caused by exposure to coal stoves or open fires, EAI has become increasingly common among individuals using space heaters, heating pads, or laptop computers near bare skin.^2,3 Although EAI itself is benign and usually resolves with the removal of the exposure, it remains of clinical importance because of its association with underlying chronic disease, as chronic pain often is managed with frequent heating pad or hot water bottle use.² Additionally, accurate diagnosis is important given the future risk for malignancy, as chronic changes of EAI have been reported to lead to squamous cell carcinoma or rarely Merkel cell carcinoma.² Erythema ab igne is not traditionally associated with the formation of bullae; however, we present a case of bullous EAI that we believe highlights the importance of including this condition in the differential diagnosis of bullous disorders.

A 55-year-old man was admitted for presumed cellulitis of the bilateral legs. The patient had developed hyperpigmented discoloration of the medial surface of both legs with subsequent formation of tense bullae over the last 2 months. The dermatology department was consulted, as there was concern for bullous pemphigoid. The patient’s medical history was notable for hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, and hepatitis C virus with cirrhosis. The patient denied pruritus, pain, or known exposure of the legs to potential irritants prior to developing the lesions; however, with additional questioning he did report frequently sitting in front of a space heater with bare legs. Physical examination revealed multiple areas of reticulated erythematous hyperpigmentation with several overlying bullae (Figure 1). Many of the bullae were unroofed with full-thickness ulceration. Biopsies were taken for hematoxylin and eosin staining (Figure 2) and direct immunofluorescence.

Basic hematologic and metabolic laboratory test results as well as blood cultures were negative. Wound culture was positive for methicillin-resistant Staphylococcus aureus. Histologic examination showed interface dermatitis with subepidermal vesicle (Figure 2). Scattered necrotic keratinocytes were present in the adjacent epidermis, and focal subtle vacuolar alteration of the dermoepidermal junction was seen (Figure 3). Sparse perivascular mononuclear cells and scattered melanophages were present in the dermis. Direct immunofluorescence showed no diagnostic immunopathologic abnormality. Focal weak nonspecific vascular positivity for IgG and C3 was seen, but IgA and IgM were negative. Although not specific, these changes were compatible with EAI in the clinical context provided. The diagnosis of bullous EAI with superimposed staphylococcal infection was made.

Although rare, there have been reports of a bullous variant of EAI. Flanagan et al⁴ described 3 cases of bullous EAI with histopathology similar to our case. All 3 biopsies showed subepidermal separation with a mild perivascular dermal lymphocytic infiltrate. Direct immunofluorescence was negative in 2 cases but showed nonspecific weak patchy deposition of IgM along the dermoepidermal junction.⁴ Although our case was negative for IgM, there was a similar weak nonspecific distribution of IgG. Kokturk et al⁵ described a case of bullous EAI in a man with repeated exposure to a space heater. The lesions showed subepidermal separation of the epidermis; increased elastic fibers; dilated dermal capillaries; melanophages in the upper dermis; and a mild, superficial, perivascular-lymphocytic infiltrate. Direct immunofluorescence showed no immune deposits.⁵ Several earlier cases of bullae associated with EAI have been reported in the literature but were thought to be bullous lichen planus superimposed on EAI.⁶ Our case, which exhibited similar historical, physical, and histopathologic findings, strengthens the argument for a defined bullous variant of EAI.

To the Editor:

Erythema ab igne (EAI) is a reticular erythematous hyperpigmentation of skin repeatedly exposed to moderate heat.¹ It usually is asymptomatic, though some patients report itching or burning at the site.² Historically caused by exposure to coal stoves or open fires, EAI has become increasingly common among individuals using space heaters, heating pads, or laptop computers near bare skin.^2,3 Although EAI itself is benign and usually resolves with the removal of the exposure, it remains of clinical importance because of its association with underlying chronic disease, as chronic pain often is managed with frequent heating pad or hot water bottle use.² Additionally, accurate diagnosis is important given the future risk for malignancy, as chronic changes of EAI have been reported to lead to squamous cell carcinoma or rarely Merkel cell carcinoma.² Erythema ab igne is not traditionally associated with the formation of bullae; however, we present a case of bullous EAI that we believe highlights the importance of including this condition in the differential diagnosis of bullous disorders.

A 55-year-old man was admitted for presumed cellulitis of the bilateral legs. The patient had developed hyperpigmented discoloration of the medial surface of both legs with subsequent formation of tense bullae over the last 2 months. The dermatology department was consulted, as there was concern for bullous pemphigoid. The patient’s medical history was notable for hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, and hepatitis C virus with cirrhosis. The patient denied pruritus, pain, or known exposure of the legs to potential irritants prior to developing the lesions; however, with additional questioning he did report frequently sitting in front of a space heater with bare legs. Physical examination revealed multiple areas of reticulated erythematous hyperpigmentation with several overlying bullae (Figure 1). Many of the bullae were unroofed with full-thickness ulceration. Biopsies were taken for hematoxylin and eosin staining (Figure 2) and direct immunofluorescence.

Basic hematologic and metabolic laboratory test results as well as blood cultures were negative. Wound culture was positive for methicillin-resistant Staphylococcus aureus. Histologic examination showed interface dermatitis with subepidermal vesicle (Figure 2). Scattered necrotic keratinocytes were present in the adjacent epidermis, and focal subtle vacuolar alteration of the dermoepidermal junction was seen (Figure 3). Sparse perivascular mononuclear cells and scattered melanophages were present in the dermis. Direct immunofluorescence showed no diagnostic immunopathologic abnormality. Focal weak nonspecific vascular positivity for IgG and C3 was seen, but IgA and IgM were negative. Although not specific, these changes were compatible with EAI in the clinical context provided. The diagnosis of bullous EAI with superimposed staphylococcal infection was made.

Although rare, there have been reports of a bullous variant of EAI. Flanagan et al⁴ described 3 cases of bullous EAI with histopathology similar to our case. All 3 biopsies showed subepidermal separation with a mild perivascular dermal lymphocytic infiltrate. Direct immunofluorescence was negative in 2 cases but showed nonspecific weak patchy deposition of IgM along the dermoepidermal junction.⁴ Although our case was negative for IgM, there was a similar weak nonspecific distribution of IgG. Kokturk et al⁵ described a case of bullous EAI in a man with repeated exposure to a space heater. The lesions showed subepidermal separation of the epidermis; increased elastic fibers; dilated dermal capillaries; melanophages in the upper dermis; and a mild, superficial, perivascular-lymphocytic infiltrate. Direct immunofluorescence showed no immune deposits.⁵ Several earlier cases of bullae associated with EAI have been reported in the literature but were thought to be bullous lichen planus superimposed on EAI.⁶ Our case, which exhibited similar historical, physical, and histopathologic findings, strengthens the argument for a defined bullous variant of EAI.

To the Editor:

Paraneoplastic acrokeratosis (PA), also known as Bazex syndrome, is a rare paraneoplastic dermatosis first described in 1965 by Bazex et al.¹ This entity is clinically characterized by dusky erythematous to violaceous keratoderma of the acral sites and commonly affects men older than 40 years. In most reported cases, there has been an underlying primary malignant neoplasm of the upper aerodigestive tract²; however, some other associated malignancies also have been reported. Skin changes tend to occur before the diagnosis of the associated tumor in 67% of cases. The cutaneous lesions usually resolve after successful treatment of the tumor and relapse in case of recurrence of the malignancy.³

A 53-year-old woman who was a smoker with no relevant medical background was referred to the dermatology department with an itching psoriasiform dermatitis on the palms and soles of 2 months' duration. There were no signs of systemic disease. Physical examination revealed well-demarcated, dusky red, thick, scaly plaques on the soles with sparing of the insteps (Figure, A). Scattered symmetric hyperkeratotic plaques were present on the palms (Figure, B). We also detected onychodystrophy on the hands. Other dermatologic findings were normal. Histologic examination of a biopsy specimen of the left sole showed hyperkeratosis, focal parakeratosis, acanthosis, hypergranulosis, and a predominantly perivascular dermal lymphocytic infiltrate.

With the diagnostic suspicion of PA, blood tests, chest radiograph, and colonoscopy were performed without revealing abnormalities. Positron emission tomography and computed tomography also was performed, showing cervical, mesenteric, retroperitoneal, and inguinal adenopathies. Histologic examination of both inguinal adenectomy and cervical lymph node biopsy revealed Bcl-2-positive in situ follicular lymphoma (ISFL). Examination of an iliac crest marrow aspirate showed minimal involvement of lymphoma (10%). Follow-up imaging performed 4 months after diagnosis showed no changes. The patient was diagnosed with a low-grade chronic lymphoproliferative disorder with histologic findings consistent with ISFL presenting with small disperse adenopathies and minimal bone marrow involvement. The hematology department opted for a wait-and-see approach with 6-month follow-up imaging.

The skin lesions were first treated with salicylic acid cream 10%, psoralen plus UVA therapy, and methotrexate 20 mg weekly for 2 months without remission. Replacing the other therapies, we initiated acitretin 25 mg daily, achieving sustained remission after 6 months of treatment, and then continued with a scaled dose reduction. The patient remained lesion free 1 year after starting the treatment, with a daily dose of 10 mg of acitretin.

Paraneoplastic acrokeratosis has been traditionally described as a paraneoplastic entity mainly associated with primary squamous cell carcinoma (SCC) of the upper aerodigestive tract or a metastatic SCC of the cervical lymph nodes with an unknown origin.^4,5 However, uncommon associations such as adenocarcinoma of the prostate, lung, esophagus, stomach, and colon; transitional cell carcinoma of the bladder; small cell carcinoma of the lung; cutaneous SCC; breast cancer; metastatic thymic carcinoma; metastatic neuroendocrine tumor; bronchial carcinoid tumor; SCC of the vulvar region; simultaneous multiple genitourinary tumors; and liposarcoma also have been described.⁶ Regarding the association with lymphoma, PA has been reported with peripheral T-cell lymphoma⁷ and Hodgkin disease⁸; however, ISFL underlying PA is rare.

Follicular lymphoma is the second most common non-Hodgkin lymphoma in Western countries and comprises approximately 20% of all lymphomas.⁹ It is slightly more prevalent in females, and the majority of patients present with advanced-stage disease. Generally considered to be an incurable disease, a watchful-waiting approach of conservative management has been advocated in most cases, deferring treatment until symptoms appear.⁹

Histology of PA is nonspecific, as in our case. However, it facilitates a differential diagnosis of major dermatoses including psoriasis vulgaris, pityriasis rubra pilaris, and lupus erythematosus.

Paraneoplastic palmoplantar keratoderma also is characteristic of Howel-Evans syndrome, which is a rare inherited condition associated with esophageal cancer. In contrast to our case, palmoplantar keratoderma in these patients usually begins around 10 years of age, is caused by a mutation in the RHBDF2 gene, and is inherited in an autosomal pattern.¹⁰

The diagnosis in our case was supported by a typical clinical picture, nonspecific histology, and the concurrent finding of the underlying lymphoma. Treatment of PA must focus on the removal of the underlying malignancy, which implies the remission of the cutaneous lesions. Taking into account that a recurrence of the primary tumor leads to a relapse of skin manifestations while distant metastases do not cause a reappearance of PA, it could be suggested that pathogenetically relevant factors are produced by the primary tumor and by lymph node metastases but not by metastases elsewhere.

In this case, due to the wait-and-see approach, a specific treatment for the skin lesions was established. Although management of the skin itself generally is ineffective, there are isolated reports of response after corticosteroids, antibiotics, antimycotics, keratolytic measures, or psoralen plus UVA therapy.⁶ Wishart¹¹ used etretinate to achieve an improvement of PA. We also achieved good response with acitretin. Retinoids are known to have antineoplastic activity, which may have been helpful in both the patient we presented and the one reported by Wishart.¹¹ In summary, we propose adding ISFL to the expanding list of malignant neoplasms associated with PA, noting the response of skin lesions after acitretin.

To the Editor:

Paraneoplastic acrokeratosis (PA), also known as Bazex syndrome, is a rare paraneoplastic dermatosis first described in 1965 by Bazex et al.¹ This entity is clinically characterized by dusky erythematous to violaceous keratoderma of the acral sites and commonly affects men older than 40 years. In most reported cases, there has been an underlying primary malignant neoplasm of the upper aerodigestive tract²; however, some other associated malignancies also have been reported. Skin changes tend to occur before the diagnosis of the associated tumor in 67% of cases. The cutaneous lesions usually resolve after successful treatment of the tumor and relapse in case of recurrence of the malignancy.³

A 53-year-old woman who was a smoker with no relevant medical background was referred to the dermatology department with an itching psoriasiform dermatitis on the palms and soles of 2 months' duration. There were no signs of systemic disease. Physical examination revealed well-demarcated, dusky red, thick, scaly plaques on the soles with sparing of the insteps (Figure, A). Scattered symmetric hyperkeratotic plaques were present on the palms (Figure, B). We also detected onychodystrophy on the hands. Other dermatologic findings were normal. Histologic examination of a biopsy specimen of the left sole showed hyperkeratosis, focal parakeratosis, acanthosis, hypergranulosis, and a predominantly perivascular dermal lymphocytic infiltrate.

With the diagnostic suspicion of PA, blood tests, chest radiograph, and colonoscopy were performed without revealing abnormalities. Positron emission tomography and computed tomography also was performed, showing cervical, mesenteric, retroperitoneal, and inguinal adenopathies. Histologic examination of both inguinal adenectomy and cervical lymph node biopsy revealed Bcl-2-positive in situ follicular lymphoma (ISFL). Examination of an iliac crest marrow aspirate showed minimal involvement of lymphoma (10%). Follow-up imaging performed 4 months after diagnosis showed no changes. The patient was diagnosed with a low-grade chronic lymphoproliferative disorder with histologic findings consistent with ISFL presenting with small disperse adenopathies and minimal bone marrow involvement. The hematology department opted for a wait-and-see approach with 6-month follow-up imaging.

The skin lesions were first treated with salicylic acid cream 10%, psoralen plus UVA therapy, and methotrexate 20 mg weekly for 2 months without remission. Replacing the other therapies, we initiated acitretin 25 mg daily, achieving sustained remission after 6 months of treatment, and then continued with a scaled dose reduction. The patient remained lesion free 1 year after starting the treatment, with a daily dose of 10 mg of acitretin.

Paraneoplastic acrokeratosis has been traditionally described as a paraneoplastic entity mainly associated with primary squamous cell carcinoma (SCC) of the upper aerodigestive tract or a metastatic SCC of the cervical lymph nodes with an unknown origin.^4,5 However, uncommon associations such as adenocarcinoma of the prostate, lung, esophagus, stomach, and colon; transitional cell carcinoma of the bladder; small cell carcinoma of the lung; cutaneous SCC; breast cancer; metastatic thymic carcinoma; metastatic neuroendocrine tumor; bronchial carcinoid tumor; SCC of the vulvar region; simultaneous multiple genitourinary tumors; and liposarcoma also have been described.⁶ Regarding the association with lymphoma, PA has been reported with peripheral T-cell lymphoma⁷ and Hodgkin disease⁸; however, ISFL underlying PA is rare.

Follicular lymphoma is the second most common non-Hodgkin lymphoma in Western countries and comprises approximately 20% of all lymphomas.⁹ It is slightly more prevalent in females, and the majority of patients present with advanced-stage disease. Generally considered to be an incurable disease, a watchful-waiting approach of conservative management has been advocated in most cases, deferring treatment until symptoms appear.⁹

Histology of PA is nonspecific, as in our case. However, it facilitates a differential diagnosis of major dermatoses including psoriasis vulgaris, pityriasis rubra pilaris, and lupus erythematosus.

Paraneoplastic palmoplantar keratoderma also is characteristic of Howel-Evans syndrome, which is a rare inherited condition associated with esophageal cancer. In contrast to our case, palmoplantar keratoderma in these patients usually begins around 10 years of age, is caused by a mutation in the RHBDF2 gene, and is inherited in an autosomal pattern.¹⁰

The diagnosis in our case was supported by a typical clinical picture, nonspecific histology, and the concurrent finding of the underlying lymphoma. Treatment of PA must focus on the removal of the underlying malignancy, which implies the remission of the cutaneous lesions. Taking into account that a recurrence of the primary tumor leads to a relapse of skin manifestations while distant metastases do not cause a reappearance of PA, it could be suggested that pathogenetically relevant factors are produced by the primary tumor and by lymph node metastases but not by metastases elsewhere.

In this case, due to the wait-and-see approach, a specific treatment for the skin lesions was established. Although management of the skin itself generally is ineffective, there are isolated reports of response after corticosteroids, antibiotics, antimycotics, keratolytic measures, or psoralen plus UVA therapy.⁶ Wishart¹¹ used etretinate to achieve an improvement of PA. We also achieved good response with acitretin. Retinoids are known to have antineoplastic activity, which may have been helpful in both the patient we presented and the one reported by Wishart.¹¹ In summary, we propose adding ISFL to the expanding list of malignant neoplasms associated with PA, noting the response of skin lesions after acitretin.

To the Editor:

Paraneoplastic acrokeratosis (PA), also known as Bazex syndrome, is a rare paraneoplastic dermatosis first described in 1965 by Bazex et al.¹ This entity is clinically characterized by dusky erythematous to violaceous keratoderma of the acral sites and commonly affects men older than 40 years. In most reported cases, there has been an underlying primary malignant neoplasm of the upper aerodigestive tract²; however, some other associated malignancies also have been reported. Skin changes tend to occur before the diagnosis of the associated tumor in 67% of cases. The cutaneous lesions usually resolve after successful treatment of the tumor and relapse in case of recurrence of the malignancy.³

A 53-year-old woman who was a smoker with no relevant medical background was referred to the dermatology department with an itching psoriasiform dermatitis on the palms and soles of 2 months' duration. There were no signs of systemic disease. Physical examination revealed well-demarcated, dusky red, thick, scaly plaques on the soles with sparing of the insteps (Figure, A). Scattered symmetric hyperkeratotic plaques were present on the palms (Figure, B). We also detected onychodystrophy on the hands. Other dermatologic findings were normal. Histologic examination of a biopsy specimen of the left sole showed hyperkeratosis, focal parakeratosis, acanthosis, hypergranulosis, and a predominantly perivascular dermal lymphocytic infiltrate.

With the diagnostic suspicion of PA, blood tests, chest radiograph, and colonoscopy were performed without revealing abnormalities. Positron emission tomography and computed tomography also was performed, showing cervical, mesenteric, retroperitoneal, and inguinal adenopathies. Histologic examination of both inguinal adenectomy and cervical lymph node biopsy revealed Bcl-2-positive in situ follicular lymphoma (ISFL). Examination of an iliac crest marrow aspirate showed minimal involvement of lymphoma (10%). Follow-up imaging performed 4 months after diagnosis showed no changes. The patient was diagnosed with a low-grade chronic lymphoproliferative disorder with histologic findings consistent with ISFL presenting with small disperse adenopathies and minimal bone marrow involvement. The hematology department opted for a wait-and-see approach with 6-month follow-up imaging.

The skin lesions were first treated with salicylic acid cream 10%, psoralen plus UVA therapy, and methotrexate 20 mg weekly for 2 months without remission. Replacing the other therapies, we initiated acitretin 25 mg daily, achieving sustained remission after 6 months of treatment, and then continued with a scaled dose reduction. The patient remained lesion free 1 year after starting the treatment, with a daily dose of 10 mg of acitretin.

Paraneoplastic acrokeratosis has been traditionally described as a paraneoplastic entity mainly associated with primary squamous cell carcinoma (SCC) of the upper aerodigestive tract or a metastatic SCC of the cervical lymph nodes with an unknown origin.^4,5 However, uncommon associations such as adenocarcinoma of the prostate, lung, esophagus, stomach, and colon; transitional cell carcinoma of the bladder; small cell carcinoma of the lung; cutaneous SCC; breast cancer; metastatic thymic carcinoma; metastatic neuroendocrine tumor; bronchial carcinoid tumor; SCC of the vulvar region; simultaneous multiple genitourinary tumors; and liposarcoma also have been described.⁶ Regarding the association with lymphoma, PA has been reported with peripheral T-cell lymphoma⁷ and Hodgkin disease⁸; however, ISFL underlying PA is rare.

Follicular lymphoma is the second most common non-Hodgkin lymphoma in Western countries and comprises approximately 20% of all lymphomas.⁹ It is slightly more prevalent in females, and the majority of patients present with advanced-stage disease. Generally considered to be an incurable disease, a watchful-waiting approach of conservative management has been advocated in most cases, deferring treatment until symptoms appear.⁹

Histology of PA is nonspecific, as in our case. However, it facilitates a differential diagnosis of major dermatoses including psoriasis vulgaris, pityriasis rubra pilaris, and lupus erythematosus.

Paraneoplastic palmoplantar keratoderma also is characteristic of Howel-Evans syndrome, which is a rare inherited condition associated with esophageal cancer. In contrast to our case, palmoplantar keratoderma in these patients usually begins around 10 years of age, is caused by a mutation in the RHBDF2 gene, and is inherited in an autosomal pattern.¹⁰

The diagnosis in our case was supported by a typical clinical picture, nonspecific histology, and the concurrent finding of the underlying lymphoma. Treatment of PA must focus on the removal of the underlying malignancy, which implies the remission of the cutaneous lesions. Taking into account that a recurrence of the primary tumor leads to a relapse of skin manifestations while distant metastases do not cause a reappearance of PA, it could be suggested that pathogenetically relevant factors are produced by the primary tumor and by lymph node metastases but not by metastases elsewhere.

In this case, due to the wait-and-see approach, a specific treatment for the skin lesions was established. Although management of the skin itself generally is ineffective, there are isolated reports of response after corticosteroids, antibiotics, antimycotics, keratolytic measures, or psoralen plus UVA therapy.⁶ Wishart¹¹ used etretinate to achieve an improvement of PA. We also achieved good response with acitretin. Retinoids are known to have antineoplastic activity, which may have been helpful in both the patient we presented and the one reported by Wishart.¹¹ In summary, we propose adding ISFL to the expanding list of malignant neoplasms associated with PA, noting the response of skin lesions after acitretin.

To the Editor:

Hereditary hypotrichosis simplex (HHS)(Online Mendelian Inheritance in Man [OMIM] 146520) is a rare form of hypotrichosis that typically presents in school-aged children as worsening hair loss localized to the scalp.¹ Most patients are unaffected at birth and otherwise healthy without abnormalities of the nails, teeth, or perspiration. Examination of the scalp reveals normal follicular ostia and absence of scale and erythema; however, decreased follicular density may be noted.¹ The histopathologic findings of HHS reveal velluslike hair follicles without associated fibrosis or inflammation.² Examination of hair follicles with light microscopy is unremarkable.^3,4 Historically, this condition has been largely regarded as autosomal dominant, with variable severity also described within families. Herein, we report a case of this rare disease in a child, with 2 family members displaying a less severe phenotype.

A 7-year-old girl presented with gradual thinning of the scalp hair of 3 to 4 years’ duration. Her mother reported the patient had normal hair density at birth. Over the next several years, she was noted to have an inability to grow lengthy hair. At approximately 3 years of age, thinning of scalp hair was identified. There was no prior history of increased shedding, hypohidrosis, or tooth or nail abnormalities. Family history revealed fine hair in her older sister and fine thin hair at the frontal scalp in her mother. Her mother reported similar inability to grow lengthy hair. Physical examination of the patient demonstrated short blonde hair with diffuse thinning of the crown (Figure 1). The longest hair was approximately 10 cm in length. Follicular ostia were without erythema or scale but notably fewer in number on the crown. Eyebrows, eyelashes, teeth, and fingernails were without abnormalities. A hair pull test was negative and hair mount revealed normal bulb and shaft. Microscopy of hair shafts under polarized light was unremarkable.

Two punch biopsies were obtained and submitted for vertical and horizontal sectioning. Sections demonstrated an intact epidermis, decreased follicle number, and small follicles with hypoplastic velluslike appearance (Figure 2). Fibrosis and inflammation were not seen; there was no increase in catagen or telogen hairs. Clinical and histopathological findings were consistent with HHS.

Hereditary hypotrichosis localized to the scalp was first described by Toribio and Quinones⁵ in 1974 in a large Spanish family presenting with normal scalp hair at birth followed by gradual diffuse hair loss. Hair loss that usually began in school-aged children with subsequent few fine hairs remaining on the scalp by the third decade of life was identified in these individuals.Eyelashes, eyebrows, pubic, axillary, and other truncal hairs were normal.⁵ Several similar cases of HHS localized to the scalp have since been reported.^2,6 Hereditary hypotrichosis simplex is inherited in an autosomal-dominant fashion, with the exception of 1 reported sporadic case.³

Research on HHS has primarily focused on genetic analyses of several affected families. Betz et al⁷ mapped the gene for HHS to band 6p21.3 in 2 families of Danish origin and in the Spanish family initially described by Toribio and Quinones.⁵ Three years later, a nonsense mutation in the CDSN gene encoding corneodesmosin was described.⁸ Despite these genetic advances, the pathogenesis of HHS and the role that corneodesmosin may play remain unclear.

Generalized forms of hypotrichosis (OMIM #605389) have long been reported and described as loss of scalp hair with involvement of eyebrows, eyelashes, and other body hair.⁹ Genetic studies have allowed for genome-wide linkage analysis, linking 3 families with this more generalized HHS phenotype to chromosome 18; specifically, an Italian family with sparse scalp and body hair but normal eyelashes and eyebrows,⁴ and 2 Pakistani families with thinning scalp hair and sparse truncal hair.¹⁰ A mutation in the APC downregulated 1 gene, APCDD1, also has been identified in these families.¹⁰ These genetic findings indicate that the generalized form of HHS is a distinct syndrome.

The differential diagnosis of HHS includes Marie-Unna hereditary hypotrichosis, loose anagen hair syndrome, trichothiodystrophy, and androgenetic alopecia. Marie-Unna hereditary hypotrichosis usually presents as near-complete absence of scalp hair at birth, development of wiry twisted hair in childhood, and progressive alopecia.³ Loose anagen hair syndrome usually demonstrates a ruffled cuticle on hair pull test and remits in late childhood. Polarization of the hair shaft can identify patients with trichothiodystrophy. Follicular miniaturization may lead one to consider early-onset androgenetic alopecia in some patients.

There is no effective treatment of HHS. Due to potential phenotypic variation, patients should be counseled that they may experience progressive or possible total loss of scalp hair by the third decade of life.^2,3,5 As with other hair loss disorders, wigs or additional over-the-counter cosmetic options may be considered.³ Currently, there are no known patient resources specific for HHS. Therefore, our patient’s family was referred to the National Alopecia Areata Foundation website (https://naaf.org/) for resources on discussing alopecia with school-aged children. The psychological impact of alopecia should not be overlooked and psychiatric referral should be provided, if needed. Examination of family members along with clinical monitoring are recommended. Genetic counseling also may be offered.³

To the Editor:

Hereditary hypotrichosis simplex (HHS)(Online Mendelian Inheritance in Man [OMIM] 146520) is a rare form of hypotrichosis that typically presents in school-aged children as worsening hair loss localized to the scalp.¹ Most patients are unaffected at birth and otherwise healthy without abnormalities of the nails, teeth, or perspiration. Examination of the scalp reveals normal follicular ostia and absence of scale and erythema; however, decreased follicular density may be noted.¹ The histopathologic findings of HHS reveal velluslike hair follicles without associated fibrosis or inflammation.² Examination of hair follicles with light microscopy is unremarkable.^3,4 Historically, this condition has been largely regarded as autosomal dominant, with variable severity also described within families. Herein, we report a case of this rare disease in a child, with 2 family members displaying a less severe phenotype.

A 7-year-old girl presented with gradual thinning of the scalp hair of 3 to 4 years’ duration. Her mother reported the patient had normal hair density at birth. Over the next several years, she was noted to have an inability to grow lengthy hair. At approximately 3 years of age, thinning of scalp hair was identified. There was no prior history of increased shedding, hypohidrosis, or tooth or nail abnormalities. Family history revealed fine hair in her older sister and fine thin hair at the frontal scalp in her mother. Her mother reported similar inability to grow lengthy hair. Physical examination of the patient demonstrated short blonde hair with diffuse thinning of the crown (Figure 1). The longest hair was approximately 10 cm in length. Follicular ostia were without erythema or scale but notably fewer in number on the crown. Eyebrows, eyelashes, teeth, and fingernails were without abnormalities. A hair pull test was negative and hair mount revealed normal bulb and shaft. Microscopy of hair shafts under polarized light was unremarkable.

Two punch biopsies were obtained and submitted for vertical and horizontal sectioning. Sections demonstrated an intact epidermis, decreased follicle number, and small follicles with hypoplastic velluslike appearance (Figure 2). Fibrosis and inflammation were not seen; there was no increase in catagen or telogen hairs. Clinical and histopathological findings were consistent with HHS.

Hereditary hypotrichosis localized to the scalp was first described by Toribio and Quinones⁵ in 1974 in a large Spanish family presenting with normal scalp hair at birth followed by gradual diffuse hair loss. Hair loss that usually began in school-aged children with subsequent few fine hairs remaining on the scalp by the third decade of life was identified in these individuals.Eyelashes, eyebrows, pubic, axillary, and other truncal hairs were normal.⁵ Several similar cases of HHS localized to the scalp have since been reported.^2,6 Hereditary hypotrichosis simplex is inherited in an autosomal-dominant fashion, with the exception of 1 reported sporadic case.³

Research on HHS has primarily focused on genetic analyses of several affected families. Betz et al⁷ mapped the gene for HHS to band 6p21.3 in 2 families of Danish origin and in the Spanish family initially described by Toribio and Quinones.⁵ Three years later, a nonsense mutation in the CDSN gene encoding corneodesmosin was described.⁸ Despite these genetic advances, the pathogenesis of HHS and the role that corneodesmosin may play remain unclear.

Generalized forms of hypotrichosis (OMIM #605389) have long been reported and described as loss of scalp hair with involvement of eyebrows, eyelashes, and other body hair.⁹ Genetic studies have allowed for genome-wide linkage analysis, linking 3 families with this more generalized HHS phenotype to chromosome 18; specifically, an Italian family with sparse scalp and body hair but normal eyelashes and eyebrows,⁴ and 2 Pakistani families with thinning scalp hair and sparse truncal hair.¹⁰ A mutation in the APC downregulated 1 gene, APCDD1, also has been identified in these families.¹⁰ These genetic findings indicate that the generalized form of HHS is a distinct syndrome.

The differential diagnosis of HHS includes Marie-Unna hereditary hypotrichosis, loose anagen hair syndrome, trichothiodystrophy, and androgenetic alopecia. Marie-Unna hereditary hypotrichosis usually presents as near-complete absence of scalp hair at birth, development of wiry twisted hair in childhood, and progressive alopecia.³ Loose anagen hair syndrome usually demonstrates a ruffled cuticle on hair pull test and remits in late childhood. Polarization of the hair shaft can identify patients with trichothiodystrophy. Follicular miniaturization may lead one to consider early-onset androgenetic alopecia in some patients.

There is no effective treatment of HHS. Due to potential phenotypic variation, patients should be counseled that they may experience progressive or possible total loss of scalp hair by the third decade of life.^2,3,5 As with other hair loss disorders, wigs or additional over-the-counter cosmetic options may be considered.³ Currently, there are no known patient resources specific for HHS. Therefore, our patient’s family was referred to the National Alopecia Areata Foundation website (https://naaf.org/) for resources on discussing alopecia with school-aged children. The psychological impact of alopecia should not be overlooked and psychiatric referral should be provided, if needed. Examination of family members along with clinical monitoring are recommended. Genetic counseling also may be offered.³

To the Editor:

Hereditary hypotrichosis simplex (HHS)(Online Mendelian Inheritance in Man [OMIM] 146520) is a rare form of hypotrichosis that typically presents in school-aged children as worsening hair loss localized to the scalp.¹ Most patients are unaffected at birth and otherwise healthy without abnormalities of the nails, teeth, or perspiration. Examination of the scalp reveals normal follicular ostia and absence of scale and erythema; however, decreased follicular density may be noted.¹ The histopathologic findings of HHS reveal velluslike hair follicles without associated fibrosis or inflammation.² Examination of hair follicles with light microscopy is unremarkable.^3,4 Historically, this condition has been largely regarded as autosomal dominant, with variable severity also described within families. Herein, we report a case of this rare disease in a child, with 2 family members displaying a less severe phenotype.

A 7-year-old girl presented with gradual thinning of the scalp hair of 3 to 4 years’ duration. Her mother reported the patient had normal hair density at birth. Over the next several years, she was noted to have an inability to grow lengthy hair. At approximately 3 years of age, thinning of scalp hair was identified. There was no prior history of increased shedding, hypohidrosis, or tooth or nail abnormalities. Family history revealed fine hair in her older sister and fine thin hair at the frontal scalp in her mother. Her mother reported similar inability to grow lengthy hair. Physical examination of the patient demonstrated short blonde hair with diffuse thinning of the crown (Figure 1). The longest hair was approximately 10 cm in length. Follicular ostia were without erythema or scale but notably fewer in number on the crown. Eyebrows, eyelashes, teeth, and fingernails were without abnormalities. A hair pull test was negative and hair mount revealed normal bulb and shaft. Microscopy of hair shafts under polarized light was unremarkable.

Two punch biopsies were obtained and submitted for vertical and horizontal sectioning. Sections demonstrated an intact epidermis, decreased follicle number, and small follicles with hypoplastic velluslike appearance (Figure 2). Fibrosis and inflammation were not seen; there was no increase in catagen or telogen hairs. Clinical and histopathological findings were consistent with HHS.

Hereditary hypotrichosis localized to the scalp was first described by Toribio and Quinones⁵ in 1974 in a large Spanish family presenting with normal scalp hair at birth followed by gradual diffuse hair loss. Hair loss that usually began in school-aged children with subsequent few fine hairs remaining on the scalp by the third decade of life was identified in these individuals.Eyelashes, eyebrows, pubic, axillary, and other truncal hairs were normal.⁵ Several similar cases of HHS localized to the scalp have since been reported.^2,6 Hereditary hypotrichosis simplex is inherited in an autosomal-dominant fashion, with the exception of 1 reported sporadic case.³

Research on HHS has primarily focused on genetic analyses of several affected families. Betz et al⁷ mapped the gene for HHS to band 6p21.3 in 2 families of Danish origin and in the Spanish family initially described by Toribio and Quinones.⁵ Three years later, a nonsense mutation in the CDSN gene encoding corneodesmosin was described.⁸ Despite these genetic advances, the pathogenesis of HHS and the role that corneodesmosin may play remain unclear.

Generalized forms of hypotrichosis (OMIM #605389) have long been reported and described as loss of scalp hair with involvement of eyebrows, eyelashes, and other body hair.⁹ Genetic studies have allowed for genome-wide linkage analysis, linking 3 families with this more generalized HHS phenotype to chromosome 18; specifically, an Italian family with sparse scalp and body hair but normal eyelashes and eyebrows,⁴ and 2 Pakistani families with thinning scalp hair and sparse truncal hair.¹⁰ A mutation in the APC downregulated 1 gene, APCDD1, also has been identified in these families.¹⁰ These genetic findings indicate that the generalized form of HHS is a distinct syndrome.

The differential diagnosis of HHS includes Marie-Unna hereditary hypotrichosis, loose anagen hair syndrome, trichothiodystrophy, and androgenetic alopecia. Marie-Unna hereditary hypotrichosis usually presents as near-complete absence of scalp hair at birth, development of wiry twisted hair in childhood, and progressive alopecia.³ Loose anagen hair syndrome usually demonstrates a ruffled cuticle on hair pull test and remits in late childhood. Polarization of the hair shaft can identify patients with trichothiodystrophy. Follicular miniaturization may lead one to consider early-onset androgenetic alopecia in some patients.

There is no effective treatment of HHS. Due to potential phenotypic variation, patients should be counseled that they may experience progressive or possible total loss of scalp hair by the third decade of life.^2,3,5 As with other hair loss disorders, wigs or additional over-the-counter cosmetic options may be considered.³ Currently, there are no known patient resources specific for HHS. Therefore, our patient’s family was referred to the National Alopecia Areata Foundation website (https://naaf.org/) for resources on discussing alopecia with school-aged children. The psychological impact of alopecia should not be overlooked and psychiatric referral should be provided, if needed. Examination of family members along with clinical monitoring are recommended. Genetic counseling also may be offered.³

To the Editor:

A 41-year-old man presented with a slowly enlarging, tender, firm lesion on the left hallux of approximately 5 months' duration that initially appeared to be a blister. He reported no history of keloids or trauma to the left foot. On examination, a 3.5-cm, flesh-colored, pedunculated, firm nodule was present on the lateral aspect of the left great hallux (Figure 1). No lymphadenopathy was found. The lesion was diagnosed at that time as a keloid and treated with intralesional steroids without response. The patient was lost to follow-up, and after 5 months he presented again with pain and drainage from the lesion. Acute drainage resolved after antibiotic therapy. A shave biopsy was performed, which revealed findings consistent with a dermatofibrosarcoma protuberans (DFSP). A chest radiograph was unremarkable. Re-excision was performed with negative margins on frozen section but with positive peripheral and deep margins on permanent sections. The patient subsequently underwent amputation of the left great toe and was lost to follow-up after the initial postoperative period.

Histopathologic examination demonstrated a polypoid spindle cell tumor that filled the dermis and invaded into the subcutaneous adipose tissue (Figure 2). The spindle cells had tapered nuclei in a honeycomb arrangement with only mild nuclear pleomorphism arranged in fascicles with a herringbone formation. Areas showed a myxoid stroma with abundant mucin (Figure 3). Immunostaining demonstrated cells strongly positive for CD34 and negative for MART (melanoma-associated antigen recognized by T cells), S-100, and smooth muscle actin immunostains.

Dermatofibrosarcoma protuberans is a sarcoma that is locally aggressive and tends to recur after surgical excision, though rare cases of metastasis involving the lungs have been reported.¹² Dermatofibrosarcoma protuberans usually affects young to middle-aged adults. Acral DFSP is rare in adults, with tumors most commonly occurring on the trunk (50%-60%), proximal extremities (20%-30%), or the head and neck (10%-15%).^1,2 A higher rate of acral DFSP has been found in children, which may be due to the increased rate of extremity trauma. Dermatofibrosarcoma protuberans commonly presents as an asymptomatic, slowly growing, indurated plaque that may be flesh colored or hyperpigmented, followed by development of erythematous firm nodules of up to several centimeters.^1,3 Dermatofibrosarcoma protuberans may be associated with a purulent exudate or ulceration, and pain may develop as the lesion grows.

Histopathologic evaluation shows an early plaque stage characterized by low cellularity, minimal nuclear atypia, and rare mitotic figures.⁴ In the nodular stage, the spindle cells are arranged as short fascicles in a storiform arrangement and infiltrate the subcutaneous tissue in a honeycomb pattern with hyperchromatic nuclei and mitotic figures. The nodules may develop myxomatous areas as well as less-differentiated foci with intersecting fascicles in a herringbone pattern. Anti-CD34 antibody immunostaining demonstrates strongly positive spindle cells, while DFSP is negative for stromelysin 3, factor XIIIa, and D2-40, which can help to differentiate DFSP from dermatofibroma.⁵ The myxoid subtype of DFSP does not differ clinically or prognostically from conventional DFSP, though its recognition can be of use in differentiating other myxoid tumors. Myxoid DFSP is nearly always positive for CD34 and negative for the neural marker S-100 protein.⁶

Some reports have demonstrated that Mohs micrographic surgery is superior to wide local excision in treatment of DFSP, as it results in fewer local recurrences and metastases.^7,8 Because of cytogenic abnormalities such as a reciprocal chromosomal (17;22) translocation or supernumerary ring chromosome derived from t(17;22) that place the PDGFB gene under the control of COL1A1 promoter, imatinib mesylate has been tested in DFSP and resulted in dramatic responses in both adults and children.^9,10 Suggested uses of imatinib include metastatic disease and locally invasive disease not suitable for surgical excision as well as a method to debulk tumors prior to resection.¹¹

To the Editor:

A 41-year-old man presented with a slowly enlarging, tender, firm lesion on the left hallux of approximately 5 months' duration that initially appeared to be a blister. He reported no history of keloids or trauma to the left foot. On examination, a 3.5-cm, flesh-colored, pedunculated, firm nodule was present on the lateral aspect of the left great hallux (Figure 1). No lymphadenopathy was found. The lesion was diagnosed at that time as a keloid and treated with intralesional steroids without response. The patient was lost to follow-up, and after 5 months he presented again with pain and drainage from the lesion. Acute drainage resolved after antibiotic therapy. A shave biopsy was performed, which revealed findings consistent with a dermatofibrosarcoma protuberans (DFSP). A chest radiograph was unremarkable. Re-excision was performed with negative margins on frozen section but with positive peripheral and deep margins on permanent sections. The patient subsequently underwent amputation of the left great toe and was lost to follow-up after the initial postoperative period.

Histopathologic examination demonstrated a polypoid spindle cell tumor that filled the dermis and invaded into the subcutaneous adipose tissue (Figure 2). The spindle cells had tapered nuclei in a honeycomb arrangement with only mild nuclear pleomorphism arranged in fascicles with a herringbone formation. Areas showed a myxoid stroma with abundant mucin (Figure 3). Immunostaining demonstrated cells strongly positive for CD34 and negative for MART (melanoma-associated antigen recognized by T cells), S-100, and smooth muscle actin immunostains.

Dermatofibrosarcoma protuberans is a sarcoma that is locally aggressive and tends to recur after surgical excision, though rare cases of metastasis involving the lungs have been reported.¹² Dermatofibrosarcoma protuberans usually affects young to middle-aged adults. Acral DFSP is rare in adults, with tumors most commonly occurring on the trunk (50%-60%), proximal extremities (20%-30%), or the head and neck (10%-15%).^1,2 A higher rate of acral DFSP has been found in children, which may be due to the increased rate of extremity trauma. Dermatofibrosarcoma protuberans commonly presents as an asymptomatic, slowly growing, indurated plaque that may be flesh colored or hyperpigmented, followed by development of erythematous firm nodules of up to several centimeters.^1,3 Dermatofibrosarcoma protuberans may be associated with a purulent exudate or ulceration, and pain may develop as the lesion grows.

Histopathologic evaluation shows an early plaque stage characterized by low cellularity, minimal nuclear atypia, and rare mitotic figures.⁴ In the nodular stage, the spindle cells are arranged as short fascicles in a storiform arrangement and infiltrate the subcutaneous tissue in a honeycomb pattern with hyperchromatic nuclei and mitotic figures. The nodules may develop myxomatous areas as well as less-differentiated foci with intersecting fascicles in a herringbone pattern. Anti-CD34 antibody immunostaining demonstrates strongly positive spindle cells, while DFSP is negative for stromelysin 3, factor XIIIa, and D2-40, which can help to differentiate DFSP from dermatofibroma.⁵ The myxoid subtype of DFSP does not differ clinically or prognostically from conventional DFSP, though its recognition can be of use in differentiating other myxoid tumors. Myxoid DFSP is nearly always positive for CD34 and negative for the neural marker S-100 protein.⁶

Some reports have demonstrated that Mohs micrographic surgery is superior to wide local excision in treatment of DFSP, as it results in fewer local recurrences and metastases.^7,8 Because of cytogenic abnormalities such as a reciprocal chromosomal (17;22) translocation or supernumerary ring chromosome derived from t(17;22) that place the PDGFB gene under the control of COL1A1 promoter, imatinib mesylate has been tested in DFSP and resulted in dramatic responses in both adults and children.^9,10 Suggested uses of imatinib include metastatic disease and locally invasive disease not suitable for surgical excision as well as a method to debulk tumors prior to resection.¹¹

To the Editor:

A 41-year-old man presented with a slowly enlarging, tender, firm lesion on the left hallux of approximately 5 months' duration that initially appeared to be a blister. He reported no history of keloids or trauma to the left foot. On examination, a 3.5-cm, flesh-colored, pedunculated, firm nodule was present on the lateral aspect of the left great hallux (Figure 1). No lymphadenopathy was found. The lesion was diagnosed at that time as a keloid and treated with intralesional steroids without response. The patient was lost to follow-up, and after 5 months he presented again with pain and drainage from the lesion. Acute drainage resolved after antibiotic therapy. A shave biopsy was performed, which revealed findings consistent with a dermatofibrosarcoma protuberans (DFSP). A chest radiograph was unremarkable. Re-excision was performed with negative margins on frozen section but with positive peripheral and deep margins on permanent sections. The patient subsequently underwent amputation of the left great toe and was lost to follow-up after the initial postoperative period.

Histopathologic examination demonstrated a polypoid spindle cell tumor that filled the dermis and invaded into the subcutaneous adipose tissue (Figure 2). The spindle cells had tapered nuclei in a honeycomb arrangement with only mild nuclear pleomorphism arranged in fascicles with a herringbone formation. Areas showed a myxoid stroma with abundant mucin (Figure 3). Immunostaining demonstrated cells strongly positive for CD34 and negative for MART (melanoma-associated antigen recognized by T cells), S-100, and smooth muscle actin immunostains.

Dermatofibrosarcoma protuberans is a sarcoma that is locally aggressive and tends to recur after surgical excision, though rare cases of metastasis involving the lungs have been reported.¹² Dermatofibrosarcoma protuberans usually affects young to middle-aged adults. Acral DFSP is rare in adults, with tumors most commonly occurring on the trunk (50%-60%), proximal extremities (20%-30%), or the head and neck (10%-15%).^1,2 A higher rate of acral DFSP has been found in children, which may be due to the increased rate of extremity trauma. Dermatofibrosarcoma protuberans commonly presents as an asymptomatic, slowly growing, indurated plaque that may be flesh colored or hyperpigmented, followed by development of erythematous firm nodules of up to several centimeters.^1,3 Dermatofibrosarcoma protuberans may be associated with a purulent exudate or ulceration, and pain may develop as the lesion grows.

Histopathologic evaluation shows an early plaque stage characterized by low cellularity, minimal nuclear atypia, and rare mitotic figures.⁴ In the nodular stage, the spindle cells are arranged as short fascicles in a storiform arrangement and infiltrate the subcutaneous tissue in a honeycomb pattern with hyperchromatic nuclei and mitotic figures. The nodules may develop myxomatous areas as well as less-differentiated foci with intersecting fascicles in a herringbone pattern. Anti-CD34 antibody immunostaining demonstrates strongly positive spindle cells, while DFSP is negative for stromelysin 3, factor XIIIa, and D2-40, which can help to differentiate DFSP from dermatofibroma.⁵ The myxoid subtype of DFSP does not differ clinically or prognostically from conventional DFSP, though its recognition can be of use in differentiating other myxoid tumors. Myxoid DFSP is nearly always positive for CD34 and negative for the neural marker S-100 protein.⁶

Some reports have demonstrated that Mohs micrographic surgery is superior to wide local excision in treatment of DFSP, as it results in fewer local recurrences and metastases.^7,8 Because of cytogenic abnormalities such as a reciprocal chromosomal (17;22) translocation or supernumerary ring chromosome derived from t(17;22) that place the PDGFB gene under the control of COL1A1 promoter, imatinib mesylate has been tested in DFSP and resulted in dramatic responses in both adults and children.^9,10 Suggested uses of imatinib include metastatic disease and locally invasive disease not suitable for surgical excision as well as a method to debulk tumors prior to resection.¹¹

To the Editor:

Temporal triangular alopecia (TTA), a condition first described by Sabouraud¹ in 1905, is a circumscribed nonscarring form of alopecia. Also referred to as congenital triangular alopecia, TTA presents as a triangular or lancet-shaped area of hair loss involving the frontotemporal hairline. Temporal triangular alopecia is characterized histologically by a normal number of miniaturized hair follicles without notable inflammation.² Although the majority of cases arise between birth and 9 years of age,^3,4 rare cases of adult-onset TTA also have been reported.^5,6 Adult-onset cases can cause notable diagnostic confusion and inappropriate treatment, as reported in our patient.

A 25-year-old woman with a history of Hashimoto thyroiditis presented with hair loss affecting the right temporal scalp of 3 years' duration that was first noticed by her husband. The lesion was an asymptomatic, 6×8-cm, roughly lancet-shaped patch of alopecia located on the right temporal scalp, bordering on the frontal hairline (Figure 1). Centrally, the patch appeared almost hairless with a few retained terminal hairs. The frontal hairline was thinned but still present. There was no scaling or erythema, and fine vellus hairs and a few isolated terminal hairs covered the area. The corresponding skin on the contralateral temporal scalp showed normal hair density. The patient insisted that she had normal hair at the affected area until 22 years of age, and she denied a history of trauma or tight hairstyles. Initially diagnosed with alopecia areata by her primary care provider, the patient was treated with topical corticosteroids for 6 months without benefit. She was subsequently referred to a dermatologist who again offered a diagnosis of alopecia areata and treated the lesions with 2 intralesional corticosteroid injections without benefit. No biopsies of the affected area were performed, and the patient was given a trial of topical minoxidil.

The patient consulted a new primary care provider and was diagnosed with scarring alopecia. She was referred to our dermatology department for further treatment. An initial biopsy at the edge of the affected area was interpreted as normal, but after failing additional intralesional corticosteroid injections, she was referred to our hair clinic where another biopsy was performed in the central portion of the lesion. A 4-mm diameter punch biopsy specimen revealed a normal epidermis and dermis; however, in the lower dermis only a single terminal follicle was seen (Figure 2). Sections through the upper dermis (Figure 3) showed that the total number of hairs was normal or nearly normal with at least 22 follicles, but most were vellus and indeterminate hairs with only a single terminal hair. The dermal architecture was otherwise normal. Given the clinical and histologic findings, a diagnosis of TTA was made. Subsequent to the diagnosis, the patient did not pursue any additional treatment options and preferred to style her hair so that the area of TTA remained covered.

The differential diagnosis in adults presenting with a patch of localized alopecia includes alopecia areata, trichotillomania, pressure-induced alopecia, traction alopecia, lichen planopilaris, discoid lupus erythematosus, and rarely TTA. Temporal triangular alopecia is a fairly common, if underreported, nonscarring form of alopecia that mainly affects young children. A PubMed search of articles indexed for MEDLINE using the terms temporal triangular alopecia or congenital triangular alopecia or triangular alopecia documented only 76 cases of TTA including our own, with the majority of patients diagnosed before 9 years of age. Only 2 cases of adult-onset TTA have been reported,^5,6 possibly leading to misdiagnosis of adult patients who present with similar areas of hair loss. As with some prior cases of TTA,^5,7 our patient was misdiagnosed with alopecia areata and scarring alopecia, both treated unsuccessfully before a diagnosis of TTA was considered. Clues to the diagnosis included the location, the lack of change in size and shape, the lack of response to intralesional corticosteroids, and the presence of numerous vellus hairs on the surface. A biopsy of the visibly hairless zone was confirmatory. The normal or nearly normal number of miniaturized hairs in specimens of TTA suggest that topical minoxidil therapy (eg, 5% solution twice daily for at least 6 months) might be useful, but the authors have tried it on a few other patients with clinically typical TTA without discernible benefit. When lesions are small, excision provides a fast and permanent solution to the problem, albeit with the usual risks of minor surgery.

To the Editor:

Temporal triangular alopecia (TTA), a condition first described by Sabouraud¹ in 1905, is a circumscribed nonscarring form of alopecia. Also referred to as congenital triangular alopecia, TTA presents as a triangular or lancet-shaped area of hair loss involving the frontotemporal hairline. Temporal triangular alopecia is characterized histologically by a normal number of miniaturized hair follicles without notable inflammation.² Although the majority of cases arise between birth and 9 years of age,^3,4 rare cases of adult-onset TTA also have been reported.^5,6 Adult-onset cases can cause notable diagnostic confusion and inappropriate treatment, as reported in our patient.

A 25-year-old woman with a history of Hashimoto thyroiditis presented with hair loss affecting the right temporal scalp of 3 years' duration that was first noticed by her husband. The lesion was an asymptomatic, 6×8-cm, roughly lancet-shaped patch of alopecia located on the right temporal scalp, bordering on the frontal hairline (Figure 1). Centrally, the patch appeared almost hairless with a few retained terminal hairs. The frontal hairline was thinned but still present. There was no scaling or erythema, and fine vellus hairs and a few isolated terminal hairs covered the area. The corresponding skin on the contralateral temporal scalp showed normal hair density. The patient insisted that she had normal hair at the affected area until 22 years of age, and she denied a history of trauma or tight hairstyles. Initially diagnosed with alopecia areata by her primary care provider, the patient was treated with topical corticosteroids for 6 months without benefit. She was subsequently referred to a dermatologist who again offered a diagnosis of alopecia areata and treated the lesions with 2 intralesional corticosteroid injections without benefit. No biopsies of the affected area were performed, and the patient was given a trial of topical minoxidil.

The patient consulted a new primary care provider and was diagnosed with scarring alopecia. She was referred to our dermatology department for further treatment. An initial biopsy at the edge of the affected area was interpreted as normal, but after failing additional intralesional corticosteroid injections, she was referred to our hair clinic where another biopsy was performed in the central portion of the lesion. A 4-mm diameter punch biopsy specimen revealed a normal epidermis and dermis; however, in the lower dermis only a single terminal follicle was seen (Figure 2). Sections through the upper dermis (Figure 3) showed that the total number of hairs was normal or nearly normal with at least 22 follicles, but most were vellus and indeterminate hairs with only a single terminal hair. The dermal architecture was otherwise normal. Given the clinical and histologic findings, a diagnosis of TTA was made. Subsequent to the diagnosis, the patient did not pursue any additional treatment options and preferred to style her hair so that the area of TTA remained covered.

The differential diagnosis in adults presenting with a patch of localized alopecia includes alopecia areata, trichotillomania, pressure-induced alopecia, traction alopecia, lichen planopilaris, discoid lupus erythematosus, and rarely TTA. Temporal triangular alopecia is a fairly common, if underreported, nonscarring form of alopecia that mainly affects young children. A PubMed search of articles indexed for MEDLINE using the terms temporal triangular alopecia or congenital triangular alopecia or triangular alopecia documented only 76 cases of TTA including our own, with the majority of patients diagnosed before 9 years of age. Only 2 cases of adult-onset TTA have been reported,^5,6 possibly leading to misdiagnosis of adult patients who present with similar areas of hair loss. As with some prior cases of TTA,^5,7 our patient was misdiagnosed with alopecia areata and scarring alopecia, both treated unsuccessfully before a diagnosis of TTA was considered. Clues to the diagnosis included the location, the lack of change in size and shape, the lack of response to intralesional corticosteroids, and the presence of numerous vellus hairs on the surface. A biopsy of the visibly hairless zone was confirmatory. The normal or nearly normal number of miniaturized hairs in specimens of TTA suggest that topical minoxidil therapy (eg, 5% solution twice daily for at least 6 months) might be useful, but the authors have tried it on a few other patients with clinically typical TTA without discernible benefit. When lesions are small, excision provides a fast and permanent solution to the problem, albeit with the usual risks of minor surgery.

To the Editor:

Temporal triangular alopecia (TTA), a condition first described by Sabouraud¹ in 1905, is a circumscribed nonscarring form of alopecia. Also referred to as congenital triangular alopecia, TTA presents as a triangular or lancet-shaped area of hair loss involving the frontotemporal hairline. Temporal triangular alopecia is characterized histologically by a normal number of miniaturized hair follicles without notable inflammation.² Although the majority of cases arise between birth and 9 years of age,^3,4 rare cases of adult-onset TTA also have been reported.^5,6 Adult-onset cases can cause notable diagnostic confusion and inappropriate treatment, as reported in our patient.

A 25-year-old woman with a history of Hashimoto thyroiditis presented with hair loss affecting the right temporal scalp of 3 years' duration that was first noticed by her husband. The lesion was an asymptomatic, 6×8-cm, roughly lancet-shaped patch of alopecia located on the right temporal scalp, bordering on the frontal hairline (Figure 1). Centrally, the patch appeared almost hairless with a few retained terminal hairs. The frontal hairline was thinned but still present. There was no scaling or erythema, and fine vellus hairs and a few isolated terminal hairs covered the area. The corresponding skin on the contralateral temporal scalp showed normal hair density. The patient insisted that she had normal hair at the affected area until 22 years of age, and she denied a history of trauma or tight hairstyles. Initially diagnosed with alopecia areata by her primary care provider, the patient was treated with topical corticosteroids for 6 months without benefit. She was subsequently referred to a dermatologist who again offered a diagnosis of alopecia areata and treated the lesions with 2 intralesional corticosteroid injections without benefit. No biopsies of the affected area were performed, and the patient was given a trial of topical minoxidil.

The patient consulted a new primary care provider and was diagnosed with scarring alopecia. She was referred to our dermatology department for further treatment. An initial biopsy at the edge of the affected area was interpreted as normal, but after failing additional intralesional corticosteroid injections, she was referred to our hair clinic where another biopsy was performed in the central portion of the lesion. A 4-mm diameter punch biopsy specimen revealed a normal epidermis and dermis; however, in the lower dermis only a single terminal follicle was seen (Figure 2). Sections through the upper dermis (Figure 3) showed that the total number of hairs was normal or nearly normal with at least 22 follicles, but most were vellus and indeterminate hairs with only a single terminal hair. The dermal architecture was otherwise normal. Given the clinical and histologic findings, a diagnosis of TTA was made. Subsequent to the diagnosis, the patient did not pursue any additional treatment options and preferred to style her hair so that the area of TTA remained covered.

The differential diagnosis in adults presenting with a patch of localized alopecia includes alopecia areata, trichotillomania, pressure-induced alopecia, traction alopecia, lichen planopilaris, discoid lupus erythematosus, and rarely TTA. Temporal triangular alopecia is a fairly common, if underreported, nonscarring form of alopecia that mainly affects young children. A PubMed search of articles indexed for MEDLINE using the terms temporal triangular alopecia or congenital triangular alopecia or triangular alopecia documented only 76 cases of TTA including our own, with the majority of patients diagnosed before 9 years of age. Only 2 cases of adult-onset TTA have been reported,^5,6 possibly leading to misdiagnosis of adult patients who present with similar areas of hair loss. As with some prior cases of TTA,^5,7 our patient was misdiagnosed with alopecia areata and scarring alopecia, both treated unsuccessfully before a diagnosis of TTA was considered. Clues to the diagnosis included the location, the lack of change in size and shape, the lack of response to intralesional corticosteroids, and the presence of numerous vellus hairs on the surface. A biopsy of the visibly hairless zone was confirmatory. The normal or nearly normal number of miniaturized hairs in specimens of TTA suggest that topical minoxidil therapy (eg, 5% solution twice daily for at least 6 months) might be useful, but the authors have tried it on a few other patients with clinically typical TTA without discernible benefit. When lesions are small, excision provides a fast and permanent solution to the problem, albeit with the usual risks of minor surgery.

To the Editor:

Netherton syndrome (NS) is a rare genodermatosis that presents with erythroderma accompanied with failure to thrive in the neonatal period. Ichthyosis linearis circumflexa, or double-edged scale, is a typical skin finding. Chronic severe atopic dermatitis with diffuse generalized xerosis usually develops and often is associated with elevated IgE levels; however, a feature most associated with and crucial for the diagnosis of NS is trichorrhexis invaginata, or bamboo hair, that causes patchy hair thinning. The triad of ichthyosis linearis circumflexa, atopic dermatitis, and trichorrhexis invaginata is diagnostic of NS. Several other clinical features, including delayed growth, skeletal age delay, and short stature also can develop during its clinical course.¹

Netherton syndrome is an autosomal-recessive disorder resulting from a mutation in the SPINK5 gene, which encodes a serine protease inhibitor important in skin barrier formation and immunity.² Thus, frequent infections are common in these patients. Current treatment options include emollients and topical anti-inflammatory agents to minimize and control the classic manifestations of NS.

A 10-year-old girl with a history of allergic rhinitis and multiple food allergies presented to the dermatology clinic with a long history of diffuse generalized xerosis and erythema with areas of lichenification and scaly patches on the face, trunk, and extremities. She was born prematurely at 34 weeks and developed scaling and erythema involving most of the body shortly after birth. She exhibited severe failure to thrive that necessitated placement of a gastrostomy feeding tube at 8 months of age, resulting in satisfactory weight gain and the tube was later removed. A liver biopsy obtained at that time revealed early intrahepatic duct obstruction and early cirrhosis. She continued to have severe atopic dermatitis, poor growth, milk intolerance, and frequent infections. She had a history of dysfunctional voiding, necessitating the use of oxybutynin. The patient also was taking desmopressin to help with insensible water losses. She had no family history of dermatologic disorders.

At presentation she had diffuse scaling and erythema around the nasal vestibule and bilateral oral commissures. She also was noted to have coarse, brittle, and sparse scalp hair and eyebrows. Her current medications included hydrocortisone cream 2.5%, loratadine 10 mg daily, desmopressin 0.1 mg twice daily, and oxybutynin. Laboratory DNA analysis revealed 2 deletion mutations involving the SPINK5 gene that combined with physical findings led to the diagnosis of NS. Due to her severe growth retardation (approximately 6 SDs below the mean), she was referred to the pediatric endocrinology department. Our patient’s skeletal age was markedly delayed (6.5 years), and she was vitamin D deficient with a total vitamin D level of 16 ng/mL (reference range, 30–80 ng/mL). She is now under the care of a dietitian and taking a vitamin D supplement of 2000 IU of vitamin D₃ daily. Growth hormone therapy trials have not been helpful.

An important feature of NS is growth retardation, which is multifactorial, resulting from increased caloric requirements, percutaneous fluid loss, and food allergies. Komatsu et al³ proposed that the SPINK5 inhibitory domain in addition to its role in skin barrier function is involved in regulating proteolytic processing of growth hormone in the pituitary gland. Its dysfunction may lead to a decrease in human growth hormone levels, resulting in short stature.³ This association suggested that our patient would be a good candidate for growth hormone therapy.

Furthermore, our patient was found to be vitamin D deficient, which was not surprising, as cholecalciferol (vitamin D₃) is synthesized in the epidermis with UV exposure. This finding suggests that vitamin D deficiency should be suspected in patients with an impaired skin barrier. In addition to calcium regulation and bone mineralization, vitamin D plays a preventative role in cardiovascular disease, autoimmune diseases such as Crohn disease and multiple sclerosis, type 2 diabetes mellitus, infectious diseases such as tuberculosis and influenza, and many cancers.⁴

Vitamin D has 2 primary derivatives: (1) vitamin D₃ from the skin and dietary animal sources, and (2) ergocalciferol (vitamin D₂), which is obtained primarily from dietary plant sources and fortified foods. The most common test for vitamin D sufficiency is an assay for serum 25-hydroxyvitamin D (25[OH]D) concentration; 25(OH)D is derived primarily from vitamin D₃, which is 3 times more potent than vitamin D₂ in the production of 25(OH)D.⁵ The American Academy of Pediatrics recommends vitamin D replacement therapy for children with 25(OH)D levels less than 20 ng/mL (50 nmol/L) or in children who are clinically symptomatic.⁶ The Endocrine Society Clinical Practice Guidelines suggest screening for vitamin D deficiency only in individuals at risk.⁷ We suggest that serum vitamin D testing should be routine in children with NS and other atopic dermatitis conditions in which UV absorption may be impaired.

To the Editor:

Netherton syndrome (NS) is a rare genodermatosis that presents with erythroderma accompanied with failure to thrive in the neonatal period. Ichthyosis linearis circumflexa, or double-edged scale, is a typical skin finding. Chronic severe atopic dermatitis with diffuse generalized xerosis usually develops and often is associated with elevated IgE levels; however, a feature most associated with and crucial for the diagnosis of NS is trichorrhexis invaginata, or bamboo hair, that causes patchy hair thinning. The triad of ichthyosis linearis circumflexa, atopic dermatitis, and trichorrhexis invaginata is diagnostic of NS. Several other clinical features, including delayed growth, skeletal age delay, and short stature also can develop during its clinical course.¹

Netherton syndrome is an autosomal-recessive disorder resulting from a mutation in the SPINK5 gene, which encodes a serine protease inhibitor important in skin barrier formation and immunity.² Thus, frequent infections are common in these patients. Current treatment options include emollients and topical anti-inflammatory agents to minimize and control the classic manifestations of NS.

A 10-year-old girl with a history of allergic rhinitis and multiple food allergies presented to the dermatology clinic with a long history of diffuse generalized xerosis and erythema with areas of lichenification and scaly patches on the face, trunk, and extremities. She was born prematurely at 34 weeks and developed scaling and erythema involving most of the body shortly after birth. She exhibited severe failure to thrive that necessitated placement of a gastrostomy feeding tube at 8 months of age, resulting in satisfactory weight gain and the tube was later removed. A liver biopsy obtained at that time revealed early intrahepatic duct obstruction and early cirrhosis. She continued to have severe atopic dermatitis, poor growth, milk intolerance, and frequent infections. She had a history of dysfunctional voiding, necessitating the use of oxybutynin. The patient also was taking desmopressin to help with insensible water losses. She had no family history of dermatologic disorders.

At presentation she had diffuse scaling and erythema around the nasal vestibule and bilateral oral commissures. She also was noted to have coarse, brittle, and sparse scalp hair and eyebrows. Her current medications included hydrocortisone cream 2.5%, loratadine 10 mg daily, desmopressin 0.1 mg twice daily, and oxybutynin. Laboratory DNA analysis revealed 2 deletion mutations involving the SPINK5 gene that combined with physical findings led to the diagnosis of NS. Due to her severe growth retardation (approximately 6 SDs below the mean), she was referred to the pediatric endocrinology department. Our patient’s skeletal age was markedly delayed (6.5 years), and she was vitamin D deficient with a total vitamin D level of 16 ng/mL (reference range, 30–80 ng/mL). She is now under the care of a dietitian and taking a vitamin D supplement of 2000 IU of vitamin D₃ daily. Growth hormone therapy trials have not been helpful.

An important feature of NS is growth retardation, which is multifactorial, resulting from increased caloric requirements, percutaneous fluid loss, and food allergies. Komatsu et al³ proposed that the SPINK5 inhibitory domain in addition to its role in skin barrier function is involved in regulating proteolytic processing of growth hormone in the pituitary gland. Its dysfunction may lead to a decrease in human growth hormone levels, resulting in short stature.³ This association suggested that our patient would be a good candidate for growth hormone therapy.

Furthermore, our patient was found to be vitamin D deficient, which was not surprising, as cholecalciferol (vitamin D₃) is synthesized in the epidermis with UV exposure. This finding suggests that vitamin D deficiency should be suspected in patients with an impaired skin barrier. In addition to calcium regulation and bone mineralization, vitamin D plays a preventative role in cardiovascular disease, autoimmune diseases such as Crohn disease and multiple sclerosis, type 2 diabetes mellitus, infectious diseases such as tuberculosis and influenza, and many cancers.⁴

Vitamin D has 2 primary derivatives: (1) vitamin D₃ from the skin and dietary animal sources, and (2) ergocalciferol (vitamin D₂), which is obtained primarily from dietary plant sources and fortified foods. The most common test for vitamin D sufficiency is an assay for serum 25-hydroxyvitamin D (25[OH]D) concentration; 25(OH)D is derived primarily from vitamin D₃, which is 3 times more potent than vitamin D₂ in the production of 25(OH)D.⁵ The American Academy of Pediatrics recommends vitamin D replacement therapy for children with 25(OH)D levels less than 20 ng/mL (50 nmol/L) or in children who are clinically symptomatic.⁶ The Endocrine Society Clinical Practice Guidelines suggest screening for vitamin D deficiency only in individuals at risk.⁷ We suggest that serum vitamin D testing should be routine in children with NS and other atopic dermatitis conditions in which UV absorption may be impaired.

To the Editor:

Netherton syndrome (NS) is a rare genodermatosis that presents with erythroderma accompanied with failure to thrive in the neonatal period. Ichthyosis linearis circumflexa, or double-edged scale, is a typical skin finding. Chronic severe atopic dermatitis with diffuse generalized xerosis usually develops and often is associated with elevated IgE levels; however, a feature most associated with and crucial for the diagnosis of NS is trichorrhexis invaginata, or bamboo hair, that causes patchy hair thinning. The triad of ichthyosis linearis circumflexa, atopic dermatitis, and trichorrhexis invaginata is diagnostic of NS. Several other clinical features, including delayed growth, skeletal age delay, and short stature also can develop during its clinical course.¹

Netherton syndrome is an autosomal-recessive disorder resulting from a mutation in the SPINK5 gene, which encodes a serine protease inhibitor important in skin barrier formation and immunity.² Thus, frequent infections are common in these patients. Current treatment options include emollients and topical anti-inflammatory agents to minimize and control the classic manifestations of NS.

A 10-year-old girl with a history of allergic rhinitis and multiple food allergies presented to the dermatology clinic with a long history of diffuse generalized xerosis and erythema with areas of lichenification and scaly patches on the face, trunk, and extremities. She was born prematurely at 34 weeks and developed scaling and erythema involving most of the body shortly after birth. She exhibited severe failure to thrive that necessitated placement of a gastrostomy feeding tube at 8 months of age, resulting in satisfactory weight gain and the tube was later removed. A liver biopsy obtained at that time revealed early intrahepatic duct obstruction and early cirrhosis. She continued to have severe atopic dermatitis, poor growth, milk intolerance, and frequent infections. She had a history of dysfunctional voiding, necessitating the use of oxybutynin. The patient also was taking desmopressin to help with insensible water losses. She had no family history of dermatologic disorders.

At presentation she had diffuse scaling and erythema around the nasal vestibule and bilateral oral commissures. She also was noted to have coarse, brittle, and sparse scalp hair and eyebrows. Her current medications included hydrocortisone cream 2.5%, loratadine 10 mg daily, desmopressin 0.1 mg twice daily, and oxybutynin. Laboratory DNA analysis revealed 2 deletion mutations involving the SPINK5 gene that combined with physical findings led to the diagnosis of NS. Due to her severe growth retardation (approximately 6 SDs below the mean), she was referred to the pediatric endocrinology department. Our patient’s skeletal age was markedly delayed (6.5 years), and she was vitamin D deficient with a total vitamin D level of 16 ng/mL (reference range, 30–80 ng/mL). She is now under the care of a dietitian and taking a vitamin D supplement of 2000 IU of vitamin D₃ daily. Growth hormone therapy trials have not been helpful.

An important feature of NS is growth retardation, which is multifactorial, resulting from increased caloric requirements, percutaneous fluid loss, and food allergies. Komatsu et al³ proposed that the SPINK5 inhibitory domain in addition to its role in skin barrier function is involved in regulating proteolytic processing of growth hormone in the pituitary gland. Its dysfunction may lead to a decrease in human growth hormone levels, resulting in short stature.³ This association suggested that our patient would be a good candidate for growth hormone therapy.

Furthermore, our patient was found to be vitamin D deficient, which was not surprising, as cholecalciferol (vitamin D₃) is synthesized in the epidermis with UV exposure. This finding suggests that vitamin D deficiency should be suspected in patients with an impaired skin barrier. In addition to calcium regulation and bone mineralization, vitamin D plays a preventative role in cardiovascular disease, autoimmune diseases such as Crohn disease and multiple sclerosis, type 2 diabetes mellitus, infectious diseases such as tuberculosis and influenza, and many cancers.⁴

Vitamin D has 2 primary derivatives: (1) vitamin D₃ from the skin and dietary animal sources, and (2) ergocalciferol (vitamin D₂), which is obtained primarily from dietary plant sources and fortified foods. The most common test for vitamin D sufficiency is an assay for serum 25-hydroxyvitamin D (25[OH]D) concentration; 25(OH)D is derived primarily from vitamin D₃, which is 3 times more potent than vitamin D₂ in the production of 25(OH)D.⁵ The American Academy of Pediatrics recommends vitamin D replacement therapy for children with 25(OH)D levels less than 20 ng/mL (50 nmol/L) or in children who are clinically symptomatic.⁶ The Endocrine Society Clinical Practice Guidelines suggest screening for vitamin D deficiency only in individuals at risk.⁷ We suggest that serum vitamin D testing should be routine in children with NS and other atopic dermatitis conditions in which UV absorption may be impaired.

To the Editor:

Melanoma-associated hypopigmentation frequently has been reported during the disease course and can include different characteristics such as regression of the primary melanoma and/or its metastases as well as common vitiligolike hypopigmentation at sites distant from the melanoma.^1,2 Among patients who present with hypopigmentation, the most common clinical presentation is hypopigmented patches in a bilateral symmetric distribution that is similar to vitiligo.¹ We report a case of segmental vitiligo–like hypopigmentation associated with melanoma.

RELATED ARTICLE: Novel Melanoma Therapies and Their Side Effects

A 37-year-old man presented with achromic patches on the right side of the neck and lower face of 2 months’ duration. He had a history of melanoma (Breslow thickness, 1.37 mm; mitotic rate, 4/mm²) on the right retroauricular region that was treated by wide local excision 12 years prior; after 10 years, he began to have headaches. At that time, imaging studies including computed tomography, magnetic resonance imaging, and positron emission tomography–computed tomography revealed multiple nodules on the brain, lungs, pancreas, left scapula, and left suprarenal gland. A lung biopsy confirmed metastatic melanoma. Intravenous fotemustine (100 mg/m² weekly for 3 weeks) was initiated, followed by maintenance treatment (100 mg/m² once daily for 5 days) every 4 weeks.

On physical examination using a Wood lamp at the current presentation 2 months later, the achromic patches were linearly distributed on the inferior portion of the right cheek (Figure). A 2×3-cm atrophic scar was present on the right retroauricular region. No regional or distant lymph nodes were enlarged or hard on examination. Although vitiligo is diagnosed using clinical findings,³ a biopsy was performed and showed absence of melanocytes at the dermoepidermal junction (hematoxylin and eosin stain) and complete absence of melanin pigment (Fontana-Masson stain). The patient was treated with topical tacrolimus with poor improvement after 2 months.

The relationship between melanoma and vitiligolike hypopigmentation is a fascinating and controversial topic. Its association is considered to be a consequence of the immune-mediated response against antigens shared by normal melanocytes and melanoma cells.⁴ Vitiligolike hypopigmentation occurs in 2.8%² of melanoma patients and is reported in metastatic disease¹ as well as those undergoing immunotherapy with or without chemotherapy.⁵ Its development in patients with stage III or IV melanoma seems to represent an independent positive prognostic factor² and correlates with a better therapeutic outcome in patients undergoing treatment with biotherapy.⁵

In most cases, the onset of achromic lesions follows the diagnosis of melanoma. Hypopigmentation appears on average 4.8 years after the initial diagnosis and approximately 1 to 2 years after lymph node or distant metastasis.¹ In our case, it occurred 12 years after the initial diagnosis and 2 years after metastatic disease was diagnosed.

Despite having widespread metastatic melanoma, our patient only developed achromic patches on the area near the prior melanoma. However, most affected patients present with hypopigmented patches in a bilateral symmetric distribution pattern similar to common vitiligo. No correlation has been found between the hypopigmentation distribution and the location of the primary tumor.¹

Because fotemustine is not likely to induce hypopigmentation, we believe that the vitiligolike hypopigmentation in our patient was related to an immune-mediated response associated with melanoma. To help explain our findings, one hypothesis considered was that cutaneous mosaicism may be involved in segmental vitiligo.⁶ The tumor may have triggered an immune response that affected a close susceptible area of mosaic vitiligo, leading to these clinical findings.

To the Editor:

Melanoma-associated hypopigmentation frequently has been reported during the disease course and can include different characteristics such as regression of the primary melanoma and/or its metastases as well as common vitiligolike hypopigmentation at sites distant from the melanoma.^1,2 Among patients who present with hypopigmentation, the most common clinical presentation is hypopigmented patches in a bilateral symmetric distribution that is similar to vitiligo.¹ We report a case of segmental vitiligo–like hypopigmentation associated with melanoma.

RELATED ARTICLE: Novel Melanoma Therapies and Their Side Effects

A 37-year-old man presented with achromic patches on the right side of the neck and lower face of 2 months’ duration. He had a history of melanoma (Breslow thickness, 1.37 mm; mitotic rate, 4/mm²) on the right retroauricular region that was treated by wide local excision 12 years prior; after 10 years, he began to have headaches. At that time, imaging studies including computed tomography, magnetic resonance imaging, and positron emission tomography–computed tomography revealed multiple nodules on the brain, lungs, pancreas, left scapula, and left suprarenal gland. A lung biopsy confirmed metastatic melanoma. Intravenous fotemustine (100 mg/m² weekly for 3 weeks) was initiated, followed by maintenance treatment (100 mg/m² once daily for 5 days) every 4 weeks.

On physical examination using a Wood lamp at the current presentation 2 months later, the achromic patches were linearly distributed on the inferior portion of the right cheek (Figure). A 2×3-cm atrophic scar was present on the right retroauricular region. No regional or distant lymph nodes were enlarged or hard on examination. Although vitiligo is diagnosed using clinical findings,³ a biopsy was performed and showed absence of melanocytes at the dermoepidermal junction (hematoxylin and eosin stain) and complete absence of melanin pigment (Fontana-Masson stain). The patient was treated with topical tacrolimus with poor improvement after 2 months.

The relationship between melanoma and vitiligolike hypopigmentation is a fascinating and controversial topic. Its association is considered to be a consequence of the immune-mediated response against antigens shared by normal melanocytes and melanoma cells.⁴ Vitiligolike hypopigmentation occurs in 2.8%² of melanoma patients and is reported in metastatic disease¹ as well as those undergoing immunotherapy with or without chemotherapy.⁵ Its development in patients with stage III or IV melanoma seems to represent an independent positive prognostic factor² and correlates with a better therapeutic outcome in patients undergoing treatment with biotherapy.⁵

In most cases, the onset of achromic lesions follows the diagnosis of melanoma. Hypopigmentation appears on average 4.8 years after the initial diagnosis and approximately 1 to 2 years after lymph node or distant metastasis.¹ In our case, it occurred 12 years after the initial diagnosis and 2 years after metastatic disease was diagnosed.

Despite having widespread metastatic melanoma, our patient only developed achromic patches on the area near the prior melanoma. However, most affected patients present with hypopigmented patches in a bilateral symmetric distribution pattern similar to common vitiligo. No correlation has been found between the hypopigmentation distribution and the location of the primary tumor.¹

Because fotemustine is not likely to induce hypopigmentation, we believe that the vitiligolike hypopigmentation in our patient was related to an immune-mediated response associated with melanoma. To help explain our findings, one hypothesis considered was that cutaneous mosaicism may be involved in segmental vitiligo.⁶ The tumor may have triggered an immune response that affected a close susceptible area of mosaic vitiligo, leading to these clinical findings.

To the Editor:

Melanoma-associated hypopigmentation frequently has been reported during the disease course and can include different characteristics such as regression of the primary melanoma and/or its metastases as well as common vitiligolike hypopigmentation at sites distant from the melanoma.^1,2 Among patients who present with hypopigmentation, the most common clinical presentation is hypopigmented patches in a bilateral symmetric distribution that is similar to vitiligo.¹ We report a case of segmental vitiligo–like hypopigmentation associated with melanoma.

RELATED ARTICLE: Novel Melanoma Therapies and Their Side Effects

A 37-year-old man presented with achromic patches on the right side of the neck and lower face of 2 months’ duration. He had a history of melanoma (Breslow thickness, 1.37 mm; mitotic rate, 4/mm²) on the right retroauricular region that was treated by wide local excision 12 years prior; after 10 years, he began to have headaches. At that time, imaging studies including computed tomography, magnetic resonance imaging, and positron emission tomography–computed tomography revealed multiple nodules on the brain, lungs, pancreas, left scapula, and left suprarenal gland. A lung biopsy confirmed metastatic melanoma. Intravenous fotemustine (100 mg/m² weekly for 3 weeks) was initiated, followed by maintenance treatment (100 mg/m² once daily for 5 days) every 4 weeks.

On physical examination using a Wood lamp at the current presentation 2 months later, the achromic patches were linearly distributed on the inferior portion of the right cheek (Figure). A 2×3-cm atrophic scar was present on the right retroauricular region. No regional or distant lymph nodes were enlarged or hard on examination. Although vitiligo is diagnosed using clinical findings,³ a biopsy was performed and showed absence of melanocytes at the dermoepidermal junction (hematoxylin and eosin stain) and complete absence of melanin pigment (Fontana-Masson stain). The patient was treated with topical tacrolimus with poor improvement after 2 months.

The relationship between melanoma and vitiligolike hypopigmentation is a fascinating and controversial topic. Its association is considered to be a consequence of the immune-mediated response against antigens shared by normal melanocytes and melanoma cells.⁴ Vitiligolike hypopigmentation occurs in 2.8%² of melanoma patients and is reported in metastatic disease¹ as well as those undergoing immunotherapy with or without chemotherapy.⁵ Its development in patients with stage III or IV melanoma seems to represent an independent positive prognostic factor² and correlates with a better therapeutic outcome in patients undergoing treatment with biotherapy.⁵

In most cases, the onset of achromic lesions follows the diagnosis of melanoma. Hypopigmentation appears on average 4.8 years after the initial diagnosis and approximately 1 to 2 years after lymph node or distant metastasis.¹ In our case, it occurred 12 years after the initial diagnosis and 2 years after metastatic disease was diagnosed.

Despite having widespread metastatic melanoma, our patient only developed achromic patches on the area near the prior melanoma. However, most affected patients present with hypopigmented patches in a bilateral symmetric distribution pattern similar to common vitiligo. No correlation has been found between the hypopigmentation distribution and the location of the primary tumor.¹

Because fotemustine is not likely to induce hypopigmentation, we believe that the vitiligolike hypopigmentation in our patient was related to an immune-mediated response associated with melanoma. To help explain our findings, one hypothesis considered was that cutaneous mosaicism may be involved in segmental vitiligo.⁶ The tumor may have triggered an immune response that affected a close susceptible area of mosaic vitiligo, leading to these clinical findings.