Dermatopathology

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

The Diagnosis: Annular Psoriasis

Because the patient's history was nonconcordant with the clinical appearance, a 4-mm punch biopsy was performed from a lesion on the left hip. Hematoxylin and eosin-stained sections demonstrated mild irregular acanthosis of the epidermis with discrete mounds of parakeratin (Figure 1A). Higher power revealed numerous neutrophils entrapped within focal scale crusts (Figure 1B). Periodic acid-Schiff stain for fungus demonstrated no hyphal elements or yeast forms in the stratum corneum. These histopathology findings were consistent with the diagnosis of annular psoriasis.

The manifestation of psoriasis may take many forms, ranging from classic plaques to pustular eruptions--either annular or generalized--and erythroderma. Primarily annular plaque-type psoriasis without pustules, however, remains an uncommon finding.¹ Psoriatic plaques may become annular or arcuate with central clearing from partial treatment with topical medications, though our patient reported annular plaques prior to any treatment. His presentation was notably different than annular pustular psoriasis in that there were no pustules in the leading edge, and there was no trailing scale, which is typical of annular pustular psoriasis.

Topical triamcinolone prescribed at the initial presentation to the dermatology department helped with pruritus, but due to the large body surface area involved, methotrexate later was initiated. After a 10-mg test dose of methotrexate and titration to 15 mg weekly, dramatic improvement in the rash was noted after 8 weeks. As the rash resolved, only faint hyperpigmented patches remained (Figure 2).

Erythema gyratum repens is a rare paraneoplastic syndrome that presents with annular scaly plaques with concentric circles with a wood grain-like appearance. The borders can advance up to 1 cm daily and show nonspecific findings on histopathology.² Due to the observation that approximately 80% of cases of erythema gyratum repens were associated with an underlying malignancy, most often of the lung,³ this diagnosis was entertained given our patient's clinical presentation.

Erythema annulare centrifugum (EAC) historically has been divided into 2 forms: superficial and deep.⁴ Both present with slowly expanding, annular, pink plaques. Superficial EAC demonstrates parakeratosis and trailing scale and has not been proven to be associated with other systemic diseases, while deep EAC has infiltrated borders without scale, and many cases of EAC may represent annular forms of tumid lupus.⁴ Inflammatory cells may cuff vessels tightly, resulting in so-called coat sleeve infiltrate in superficial EAC. Along with trailing scale, this finding suggests the diagnosis. It has been argued that EAC is not an entity on its own and should prompt evaluation for lupus erythematosus, dermatitis, hypersensitivity to tinea pedis, and Lyme disease in appropriate circumstances.⁵

Tinea corporis always should be considered when evaluating annular scaly plaques with central clearing. Diagnosis and treatment are straightforward when hyphae are found on microscopy of skin scrapings or seen on periodic acid-Schiff stains of formalin-fixed tissue. Tinea imbricata presents with an interesting morphology and appears more ornate or cerebriform than tinea corporis caused by Trichophyton rubrum. It is caused by infection with Trichophyton circumscriptum and occurs in certain regions in the South Pacific, Southeast Asia, and Central and South America, making the diagnosis within the United States unlikely for a patient who has not traveled to these areas.⁶

Erythema chronicum migrans is diagnostic of Lyme disease infection with Borrelia burgdorferi, and solitary lesions occur surrounding the site of a tick bite in the majority of patients. Only 20% of patients will develop multiple lesions consistent with erythema chronicum migrans due to multiple tick bites, spirochetemia, or lymphatic spread.⁷ Up to one-third of patients are unaware that they were bitten by a tick. In endemic areas, this diagnosis must be entertained in any patient presenting with an annular rash, as treatment may prevent notable morbidity.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

To the Editor:

An 84-year-old man was admitted to the hospital with 5 erythematous cutaneous nodules of several days’ duration on the legs ranging in size from 1.0 to 1.5 cm. Upon admission, the patient also had a chest radiograph suspicious for pneumonia. The patient had received sulfamethoxazole/trimethoprim for a urinary tract infection as an outpatient 5 days prior to presentation, but he stopped the medication due to the appearance of the cutaneous nodules. Of note, the patient also reported unintentional weight loss of 15 pounds over the last few months.

New nodules had developed at a rate of 1 to 2 lesions daily in the 3 days prior to presentation and continued to develop after admission to the hospital. The nodules appeared as tender, erythematous lesions that evolved to form pustules and developed overlying crusts in later stages (Figure 1). They were limited to the arms and legs, primarily involving the lower legs. There was no evidence of oral or ocular involvement. A hemoglobin count of 10.9 g/dL (reference range, 14.0–17.5 g/dL), white blood cell count of 8.8×10⁹/L (reference range, 4.5–11.0×10⁹/L), and erythrocyte sedimentation rate of 69 mm/h (reference range, 0–20 mm/h) were noted on admission.

The patient was started on ceftriaxone and azithromycin for suspected pneumonia. The differential diagnosis for the cutaneous nodules included lymphoma, acid-fast bacilli (AFB) infection, deep fungal infection, pyoderma gangrenosum, Sweet syndrome (SS), panniculitis, erythema elevatum diutinum, and polyarteritis nodosa. A punch biopsy of a nodule on the left foot was performed. Histopathology demonstrated a neutrophilic panniculitis (Figure 2) with an epidermal abscess. No vasculitis was identified, and periodic acid–Schiff and AFB staining of the skin biopsy were negative. These findings were consistent with SS. Computed tomography scans of the chest, abdomen, and pelvis, which were completed early in the course of hospitalization due to concern for underlying malignancy, revealed pericardial and pleural effusions as well as cystic lesions in the lungs, spleen, kidneys, and prostate, with the largest lesion on the spleen measuring 5.6×4.8 cm (Figure 3). Computed tomography scanning was negative for areas of consolidation in the lungs. A splenic biopsy was performed by an interventional radiologist during the patient's hospitalization that identified an aseptic, neutrophilic process. Fungal, bacterial, and AFB cultures of the splenic tissue and cystic contents were negative. Bilateral pleural effusions also were identified, and a thoracentesis was performed. The pleural fluid indicated rare mesothelial cells in the background of acute inflammation with no growth of the bacterial, fungal, or AFB cultures.

Our case could be consistent with either drug-induced or malignancy-associated SS. Sweet syndrome initially was described in 1964 in 8 female patients with leukocytosis and cutaneous plaques infiltrated by neutrophils.¹ The skin lesions typically are red and painful, ranging in size from 0.5 cm to 12.0 cm, and can last weeks to years if not treated.² Variations of skin lesions include bullous and pustular morphologies.³

Diagnostic criteria for SS have been established.⁴ Both of the major criteria must be met as well as 2 of 4 minor criteria. Major criteria include abrupt onset of tender erythematous plaques and nodules; secondly, a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis must be seen on histopathology. Minor criteria include pyrexia, association with underlying condition (malignancy, pregnancy, drug exposure, inflammatory disorder), responsiveness to systemic steroids, and abnormal laboratory values (erythrocyte sedimentation rate, white blood cell count, C-reactive protein, neutrophilia).⁴

Sweet syndrome can be divided into 3 classifications: classical or idiopathic, drug-induced, or malignancy-associated.⁴ Classical SS most commonly is seen in middle-aged women after an upper respiratory or gastrointestinal infection. Drug-induced SS most often is associated with granulocyte-stimulating factor colony therapy⁴; however, it has been associated with use of trimethoprim/sulfamethoxazole.⁵ Malignancy-associated SS most commonly is seen in individuals with hematologic malignancy, specifically acute myeloid leukemia. Although its association with multiple myeloma is not as frequent, cases of malignancy-associated SS identifying this association have been reported.^6,7 Mucosal involvement in the form of aphthouslike lesions more frequently is seen in malignancy-associated SS.⁸ Differing from classical SS, which has a female predilection of around 4:1, the malignancy-associated disorder has a 1:1 female-to-male ratio.⁴

In the majority of cases of SS, the neutrophilic infiltrate is in the papillary and upper reticular dermis; however, if the neutrophilic infiltrate is predominately in the subcutaneous tissue (known as subcutaneous SS), there is a strong association with malignancy.⁹ The histopathology in our case demonstrated a neutrophilic infiltrate in the subcutaneous tissue.

Fever is the most common systemic manifestation of SS and is present in 54% to 65% of patients.^8,10 Besides the skin, the most common site affected is the eye, with 13% to 75% of patients reporting ocular involvement, usually conjunctivitis.^4,10 Although infrequent, extracutaneous SS has been identified in the bones, central nervous system, kidneys, heart, liver, spleen, lungs, ears, eyes, and intestines.⁴ A case of SS with splenic involvement in the form of sterile abscesses also was reported.¹¹ This case was related to parvovirus B19.

Sweet syndrome is a condition characterized by tender, erythematous cutaneous lesions with histopathology demonstrating neutrophilic infiltrate in the absence of vasculitis. We report a case of suspected extracutaneous SS in the form of splenic cysts in a patient whose SS was associated with malignancy and/or drug ingestion.

To the Editor:

An 84-year-old man was admitted to the hospital with 5 erythematous cutaneous nodules of several days’ duration on the legs ranging in size from 1.0 to 1.5 cm. Upon admission, the patient also had a chest radiograph suspicious for pneumonia. The patient had received sulfamethoxazole/trimethoprim for a urinary tract infection as an outpatient 5 days prior to presentation, but he stopped the medication due to the appearance of the cutaneous nodules. Of note, the patient also reported unintentional weight loss of 15 pounds over the last few months.

New nodules had developed at a rate of 1 to 2 lesions daily in the 3 days prior to presentation and continued to develop after admission to the hospital. The nodules appeared as tender, erythematous lesions that evolved to form pustules and developed overlying crusts in later stages (Figure 1). They were limited to the arms and legs, primarily involving the lower legs. There was no evidence of oral or ocular involvement. A hemoglobin count of 10.9 g/dL (reference range, 14.0–17.5 g/dL), white blood cell count of 8.8×10⁹/L (reference range, 4.5–11.0×10⁹/L), and erythrocyte sedimentation rate of 69 mm/h (reference range, 0–20 mm/h) were noted on admission.

The patient was started on ceftriaxone and azithromycin for suspected pneumonia. The differential diagnosis for the cutaneous nodules included lymphoma, acid-fast bacilli (AFB) infection, deep fungal infection, pyoderma gangrenosum, Sweet syndrome (SS), panniculitis, erythema elevatum diutinum, and polyarteritis nodosa. A punch biopsy of a nodule on the left foot was performed. Histopathology demonstrated a neutrophilic panniculitis (Figure 2) with an epidermal abscess. No vasculitis was identified, and periodic acid–Schiff and AFB staining of the skin biopsy were negative. These findings were consistent with SS. Computed tomography scans of the chest, abdomen, and pelvis, which were completed early in the course of hospitalization due to concern for underlying malignancy, revealed pericardial and pleural effusions as well as cystic lesions in the lungs, spleen, kidneys, and prostate, with the largest lesion on the spleen measuring 5.6×4.8 cm (Figure 3). Computed tomography scanning was negative for areas of consolidation in the lungs. A splenic biopsy was performed by an interventional radiologist during the patient's hospitalization that identified an aseptic, neutrophilic process. Fungal, bacterial, and AFB cultures of the splenic tissue and cystic contents were negative. Bilateral pleural effusions also were identified, and a thoracentesis was performed. The pleural fluid indicated rare mesothelial cells in the background of acute inflammation with no growth of the bacterial, fungal, or AFB cultures.

Our case could be consistent with either drug-induced or malignancy-associated SS. Sweet syndrome initially was described in 1964 in 8 female patients with leukocytosis and cutaneous plaques infiltrated by neutrophils.¹ The skin lesions typically are red and painful, ranging in size from 0.5 cm to 12.0 cm, and can last weeks to years if not treated.² Variations of skin lesions include bullous and pustular morphologies.³

Diagnostic criteria for SS have been established.⁴ Both of the major criteria must be met as well as 2 of 4 minor criteria. Major criteria include abrupt onset of tender erythematous plaques and nodules; secondly, a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis must be seen on histopathology. Minor criteria include pyrexia, association with underlying condition (malignancy, pregnancy, drug exposure, inflammatory disorder), responsiveness to systemic steroids, and abnormal laboratory values (erythrocyte sedimentation rate, white blood cell count, C-reactive protein, neutrophilia).⁴

Sweet syndrome can be divided into 3 classifications: classical or idiopathic, drug-induced, or malignancy-associated.⁴ Classical SS most commonly is seen in middle-aged women after an upper respiratory or gastrointestinal infection. Drug-induced SS most often is associated with granulocyte-stimulating factor colony therapy⁴; however, it has been associated with use of trimethoprim/sulfamethoxazole.⁵ Malignancy-associated SS most commonly is seen in individuals with hematologic malignancy, specifically acute myeloid leukemia. Although its association with multiple myeloma is not as frequent, cases of malignancy-associated SS identifying this association have been reported.^6,7 Mucosal involvement in the form of aphthouslike lesions more frequently is seen in malignancy-associated SS.⁸ Differing from classical SS, which has a female predilection of around 4:1, the malignancy-associated disorder has a 1:1 female-to-male ratio.⁴

In the majority of cases of SS, the neutrophilic infiltrate is in the papillary and upper reticular dermis; however, if the neutrophilic infiltrate is predominately in the subcutaneous tissue (known as subcutaneous SS), there is a strong association with malignancy.⁹ The histopathology in our case demonstrated a neutrophilic infiltrate in the subcutaneous tissue.

Fever is the most common systemic manifestation of SS and is present in 54% to 65% of patients.^8,10 Besides the skin, the most common site affected is the eye, with 13% to 75% of patients reporting ocular involvement, usually conjunctivitis.^4,10 Although infrequent, extracutaneous SS has been identified in the bones, central nervous system, kidneys, heart, liver, spleen, lungs, ears, eyes, and intestines.⁴ A case of SS with splenic involvement in the form of sterile abscesses also was reported.¹¹ This case was related to parvovirus B19.

Sweet syndrome is a condition characterized by tender, erythematous cutaneous lesions with histopathology demonstrating neutrophilic infiltrate in the absence of vasculitis. We report a case of suspected extracutaneous SS in the form of splenic cysts in a patient whose SS was associated with malignancy and/or drug ingestion.

To the Editor:

An 84-year-old man was admitted to the hospital with 5 erythematous cutaneous nodules of several days’ duration on the legs ranging in size from 1.0 to 1.5 cm. Upon admission, the patient also had a chest radiograph suspicious for pneumonia. The patient had received sulfamethoxazole/trimethoprim for a urinary tract infection as an outpatient 5 days prior to presentation, but he stopped the medication due to the appearance of the cutaneous nodules. Of note, the patient also reported unintentional weight loss of 15 pounds over the last few months.

New nodules had developed at a rate of 1 to 2 lesions daily in the 3 days prior to presentation and continued to develop after admission to the hospital. The nodules appeared as tender, erythematous lesions that evolved to form pustules and developed overlying crusts in later stages (Figure 1). They were limited to the arms and legs, primarily involving the lower legs. There was no evidence of oral or ocular involvement. A hemoglobin count of 10.9 g/dL (reference range, 14.0–17.5 g/dL), white blood cell count of 8.8×10⁹/L (reference range, 4.5–11.0×10⁹/L), and erythrocyte sedimentation rate of 69 mm/h (reference range, 0–20 mm/h) were noted on admission.

The patient was started on ceftriaxone and azithromycin for suspected pneumonia. The differential diagnosis for the cutaneous nodules included lymphoma, acid-fast bacilli (AFB) infection, deep fungal infection, pyoderma gangrenosum, Sweet syndrome (SS), panniculitis, erythema elevatum diutinum, and polyarteritis nodosa. A punch biopsy of a nodule on the left foot was performed. Histopathology demonstrated a neutrophilic panniculitis (Figure 2) with an epidermal abscess. No vasculitis was identified, and periodic acid–Schiff and AFB staining of the skin biopsy were negative. These findings were consistent with SS. Computed tomography scans of the chest, abdomen, and pelvis, which were completed early in the course of hospitalization due to concern for underlying malignancy, revealed pericardial and pleural effusions as well as cystic lesions in the lungs, spleen, kidneys, and prostate, with the largest lesion on the spleen measuring 5.6×4.8 cm (Figure 3). Computed tomography scanning was negative for areas of consolidation in the lungs. A splenic biopsy was performed by an interventional radiologist during the patient's hospitalization that identified an aseptic, neutrophilic process. Fungal, bacterial, and AFB cultures of the splenic tissue and cystic contents were negative. Bilateral pleural effusions also were identified, and a thoracentesis was performed. The pleural fluid indicated rare mesothelial cells in the background of acute inflammation with no growth of the bacterial, fungal, or AFB cultures.

Our case could be consistent with either drug-induced or malignancy-associated SS. Sweet syndrome initially was described in 1964 in 8 female patients with leukocytosis and cutaneous plaques infiltrated by neutrophils.¹ The skin lesions typically are red and painful, ranging in size from 0.5 cm to 12.0 cm, and can last weeks to years if not treated.² Variations of skin lesions include bullous and pustular morphologies.³

Diagnostic criteria for SS have been established.⁴ Both of the major criteria must be met as well as 2 of 4 minor criteria. Major criteria include abrupt onset of tender erythematous plaques and nodules; secondly, a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis must be seen on histopathology. Minor criteria include pyrexia, association with underlying condition (malignancy, pregnancy, drug exposure, inflammatory disorder), responsiveness to systemic steroids, and abnormal laboratory values (erythrocyte sedimentation rate, white blood cell count, C-reactive protein, neutrophilia).⁴

Sweet syndrome can be divided into 3 classifications: classical or idiopathic, drug-induced, or malignancy-associated.⁴ Classical SS most commonly is seen in middle-aged women after an upper respiratory or gastrointestinal infection. Drug-induced SS most often is associated with granulocyte-stimulating factor colony therapy⁴; however, it has been associated with use of trimethoprim/sulfamethoxazole.⁵ Malignancy-associated SS most commonly is seen in individuals with hematologic malignancy, specifically acute myeloid leukemia. Although its association with multiple myeloma is not as frequent, cases of malignancy-associated SS identifying this association have been reported.^6,7 Mucosal involvement in the form of aphthouslike lesions more frequently is seen in malignancy-associated SS.⁸ Differing from classical SS, which has a female predilection of around 4:1, the malignancy-associated disorder has a 1:1 female-to-male ratio.⁴

In the majority of cases of SS, the neutrophilic infiltrate is in the papillary and upper reticular dermis; however, if the neutrophilic infiltrate is predominately in the subcutaneous tissue (known as subcutaneous SS), there is a strong association with malignancy.⁹ The histopathology in our case demonstrated a neutrophilic infiltrate in the subcutaneous tissue.

Fever is the most common systemic manifestation of SS and is present in 54% to 65% of patients.^8,10 Besides the skin, the most common site affected is the eye, with 13% to 75% of patients reporting ocular involvement, usually conjunctivitis.^4,10 Although infrequent, extracutaneous SS has been identified in the bones, central nervous system, kidneys, heart, liver, spleen, lungs, ears, eyes, and intestines.⁴ A case of SS with splenic involvement in the form of sterile abscesses also was reported.¹¹ This case was related to parvovirus B19.

Sweet syndrome is a condition characterized by tender, erythematous cutaneous lesions with histopathology demonstrating neutrophilic infiltrate in the absence of vasculitis. We report a case of suspected extracutaneous SS in the form of splenic cysts in a patient whose SS was associated with malignancy and/or drug ingestion.

The Diagnosis: Erythrasma

Erythrasma usually involves intertriginous areas (eg, axillae, groin, inframammary area). Patients present with well-demarcated, minimally scaly, red-brown patches. The interdigital web space of the toes also can be involved with macerated white plaques, often with coexistent dermatophyte infection. Corynebacterium minutissimum, the bacteria responsible for erythrasma, produces coproporphyrin type III, which emits coral red fluorescence under Wood lamp examination.¹ Bathing may result in removal of the porphyrin and result in a false-negative finding. Potassium hydroxide preparation of skin scrapings can show chains of bacilli. Biopsy appears relatively normal at low power but reveals compact orthokeratosis with coccobacilli and filamentous organisms in the superficial stratum corneum (quiz image). When not obvious on hematoxylin and eosin-stained sections, the organisms are Gram-positive and also are seen with periodic acid-Schiff (PAS) and methenamine silver stains. Unlike fungal hyphae, these organisms are thinner and nonrefractile. Inflammation typically is minimal. Due to the subtle histologic findings at low power, erythrasma is considered one of the invisible dermatoses.² The differential diagnosis of these inconspicuous dermatoses that appear normal at first glance can be approached in a stepwise fashion starting in the stratum corneum, followed by the granular layer, basal layer, dermal papillae, dermal inflammatory cells, dermal connective tissue, and eccrine glands, and should consider each of the following diagnoses: candidiasis, dermatophytosis, ichthyosis vulgaris, vitiligo, macular amyloid, urticaria, telangiectasia macularis eruptiva perstans, connective tissue nevus, and argyria.² 

Candidiasis, most commonly caused by Candida albicans, usually involves the oral cavity (eg, thrush, median rhomboid glossitis, angular cheilitis), intertriginous zones, nail fold (paronychia), genital areas (eg, vulvovaginitis, balanitis), and diaper area.³ The web space between the third and fourth fingers (erosio interdigitalis blastomycetica) can be involved in patients whose hands are frequently in water. Intertriginous candidiasis presents with bright red, sometimes erosive patches with satellite lesions. Spores and mycelia (filamentous forms) are noted on potassium hydroxide preparation of skin scrapings. Histologically, the epidermis often is acanthotic, mildly spongiotic, and contains groups of neutrophils in the superficial layers. The mnemonic device for diseases with clusters of neutrophils in the stratum corneum is PTICSS (psoriasis, tinea, impetigo, candida, seborrheic dermatitis, syphilis).² Yeast, pseudohyphae, and even true hyphae can be seen in the stratum corneum with hematoxylin and eosin-stained sections and PAS. The filamentous forms tend to be vertically oriented in relation to the skin surface (Figure 1) compared to dermatophyte hyphae that tend to be parallel to the surface.²

Pitted keratolysis is a superficial bacterial infection involving the soles of the feet. The classic clinical findings are shallow 1- to 2-mm pits in clusters that can coalesce on pressure-bearing areas. Hyperhidrosis, malodor, and maceration commonly are associated. Microscopic examination reveals clusters of small cocci and filamentous bacteria located in the dell or pit of a thick compact orthokeratotic stratum corneum of acral skin with no notable inflammatory infiltrate (Figure 2).² Special stains such as Gram, methenamine silver, or PAS can assist in visualization of the organisms. Pitted keratolysis is caused by Dermatophilus congolensis and Kytococcus sedentarius (formerly Micrococcus sedentarius), which produce keratinolytic enzymes causing the defect in the stratum corneum.³

Tinea cruris, also known as jock itch and ringworm of the groin, presents with advancing pruritic, circinate, erythematous, scaling patches with central clearing on the inner thighs and crural folds. Similar to tinea pedis, Trichophyton rubrum is the most common dermatophyte to cause tinea cruris.⁴ Potassium hydroxide preparation of skin scrapings from the advancing border show fungal hyphae that cross the keratin cell borders. The histopathology of dermatophyte infections can be subtle and resemble normal skin before close inspection of the stratum corneum, which can show compact orthokeratosis, neutrophils, or "sandwich sign" where hyphae are sandwiched between an upper basket weave layer and a lower compact cornified layer (orthokeratotic or parakeratotic)(Figure 3).¹ The presence of these patterns in the stratum corneum should result in performance of PAS to highlight obscure hyphae.

Tinea versicolor, also called pityriasis versicolor, usually presents with hypopigmented or less commonly hyperpigmented circular patches that coalesce on the upper trunk and shoulders. There is a fine fluffy scale that is most notable after scraping the skin for a potassium hydroxide preparation, which shows "spaghetti and meatballs" (hyphae and spores). Tinea versicolor typically is caused by the mycelial phase of the lipophilic yeast Malassezia globosae.³ Histologically, there are yeast and short septate hyphae scattered in a loose basket weave hyperkeratotic stratum corneum with minimal or no inflammation (Figure 4). On occasion, PAS is required for identification.

The Diagnosis: Erythrasma

Erythrasma usually involves intertriginous areas (eg, axillae, groin, inframammary area). Patients present with well-demarcated, minimally scaly, red-brown patches. The interdigital web space of the toes also can be involved with macerated white plaques, often with coexistent dermatophyte infection. Corynebacterium minutissimum, the bacteria responsible for erythrasma, produces coproporphyrin type III, which emits coral red fluorescence under Wood lamp examination.¹ Bathing may result in removal of the porphyrin and result in a false-negative finding. Potassium hydroxide preparation of skin scrapings can show chains of bacilli. Biopsy appears relatively normal at low power but reveals compact orthokeratosis with coccobacilli and filamentous organisms in the superficial stratum corneum (quiz image). When not obvious on hematoxylin and eosin-stained sections, the organisms are Gram-positive and also are seen with periodic acid-Schiff (PAS) and methenamine silver stains. Unlike fungal hyphae, these organisms are thinner and nonrefractile. Inflammation typically is minimal. Due to the subtle histologic findings at low power, erythrasma is considered one of the invisible dermatoses.² The differential diagnosis of these inconspicuous dermatoses that appear normal at first glance can be approached in a stepwise fashion starting in the stratum corneum, followed by the granular layer, basal layer, dermal papillae, dermal inflammatory cells, dermal connective tissue, and eccrine glands, and should consider each of the following diagnoses: candidiasis, dermatophytosis, ichthyosis vulgaris, vitiligo, macular amyloid, urticaria, telangiectasia macularis eruptiva perstans, connective tissue nevus, and argyria.² 

Candidiasis, most commonly caused by Candida albicans, usually involves the oral cavity (eg, thrush, median rhomboid glossitis, angular cheilitis), intertriginous zones, nail fold (paronychia), genital areas (eg, vulvovaginitis, balanitis), and diaper area.³ The web space between the third and fourth fingers (erosio interdigitalis blastomycetica) can be involved in patients whose hands are frequently in water. Intertriginous candidiasis presents with bright red, sometimes erosive patches with satellite lesions. Spores and mycelia (filamentous forms) are noted on potassium hydroxide preparation of skin scrapings. Histologically, the epidermis often is acanthotic, mildly spongiotic, and contains groups of neutrophils in the superficial layers. The mnemonic device for diseases with clusters of neutrophils in the stratum corneum is PTICSS (psoriasis, tinea, impetigo, candida, seborrheic dermatitis, syphilis).² Yeast, pseudohyphae, and even true hyphae can be seen in the stratum corneum with hematoxylin and eosin-stained sections and PAS. The filamentous forms tend to be vertically oriented in relation to the skin surface (Figure 1) compared to dermatophyte hyphae that tend to be parallel to the surface.²

Pitted keratolysis is a superficial bacterial infection involving the soles of the feet. The classic clinical findings are shallow 1- to 2-mm pits in clusters that can coalesce on pressure-bearing areas. Hyperhidrosis, malodor, and maceration commonly are associated. Microscopic examination reveals clusters of small cocci and filamentous bacteria located in the dell or pit of a thick compact orthokeratotic stratum corneum of acral skin with no notable inflammatory infiltrate (Figure 2).² Special stains such as Gram, methenamine silver, or PAS can assist in visualization of the organisms. Pitted keratolysis is caused by Dermatophilus congolensis and Kytococcus sedentarius (formerly Micrococcus sedentarius), which produce keratinolytic enzymes causing the defect in the stratum corneum.³

Tinea cruris, also known as jock itch and ringworm of the groin, presents with advancing pruritic, circinate, erythematous, scaling patches with central clearing on the inner thighs and crural folds. Similar to tinea pedis, Trichophyton rubrum is the most common dermatophyte to cause tinea cruris.⁴ Potassium hydroxide preparation of skin scrapings from the advancing border show fungal hyphae that cross the keratin cell borders. The histopathology of dermatophyte infections can be subtle and resemble normal skin before close inspection of the stratum corneum, which can show compact orthokeratosis, neutrophils, or "sandwich sign" where hyphae are sandwiched between an upper basket weave layer and a lower compact cornified layer (orthokeratotic or parakeratotic)(Figure 3).¹ The presence of these patterns in the stratum corneum should result in performance of PAS to highlight obscure hyphae.

Tinea versicolor, also called pityriasis versicolor, usually presents with hypopigmented or less commonly hyperpigmented circular patches that coalesce on the upper trunk and shoulders. There is a fine fluffy scale that is most notable after scraping the skin for a potassium hydroxide preparation, which shows "spaghetti and meatballs" (hyphae and spores). Tinea versicolor typically is caused by the mycelial phase of the lipophilic yeast Malassezia globosae.³ Histologically, there are yeast and short septate hyphae scattered in a loose basket weave hyperkeratotic stratum corneum with minimal or no inflammation (Figure 4). On occasion, PAS is required for identification.

The Diagnosis: Erythrasma

Erythrasma usually involves intertriginous areas (eg, axillae, groin, inframammary area). Patients present with well-demarcated, minimally scaly, red-brown patches. The interdigital web space of the toes also can be involved with macerated white plaques, often with coexistent dermatophyte infection. Corynebacterium minutissimum, the bacteria responsible for erythrasma, produces coproporphyrin type III, which emits coral red fluorescence under Wood lamp examination.¹ Bathing may result in removal of the porphyrin and result in a false-negative finding. Potassium hydroxide preparation of skin scrapings can show chains of bacilli. Biopsy appears relatively normal at low power but reveals compact orthokeratosis with coccobacilli and filamentous organisms in the superficial stratum corneum (quiz image). When not obvious on hematoxylin and eosin-stained sections, the organisms are Gram-positive and also are seen with periodic acid-Schiff (PAS) and methenamine silver stains. Unlike fungal hyphae, these organisms are thinner and nonrefractile. Inflammation typically is minimal. Due to the subtle histologic findings at low power, erythrasma is considered one of the invisible dermatoses.² The differential diagnosis of these inconspicuous dermatoses that appear normal at first glance can be approached in a stepwise fashion starting in the stratum corneum, followed by the granular layer, basal layer, dermal papillae, dermal inflammatory cells, dermal connective tissue, and eccrine glands, and should consider each of the following diagnoses: candidiasis, dermatophytosis, ichthyosis vulgaris, vitiligo, macular amyloid, urticaria, telangiectasia macularis eruptiva perstans, connective tissue nevus, and argyria.² 

Candidiasis, most commonly caused by Candida albicans, usually involves the oral cavity (eg, thrush, median rhomboid glossitis, angular cheilitis), intertriginous zones, nail fold (paronychia), genital areas (eg, vulvovaginitis, balanitis), and diaper area.³ The web space between the third and fourth fingers (erosio interdigitalis blastomycetica) can be involved in patients whose hands are frequently in water. Intertriginous candidiasis presents with bright red, sometimes erosive patches with satellite lesions. Spores and mycelia (filamentous forms) are noted on potassium hydroxide preparation of skin scrapings. Histologically, the epidermis often is acanthotic, mildly spongiotic, and contains groups of neutrophils in the superficial layers. The mnemonic device for diseases with clusters of neutrophils in the stratum corneum is PTICSS (psoriasis, tinea, impetigo, candida, seborrheic dermatitis, syphilis).² Yeast, pseudohyphae, and even true hyphae can be seen in the stratum corneum with hematoxylin and eosin-stained sections and PAS. The filamentous forms tend to be vertically oriented in relation to the skin surface (Figure 1) compared to dermatophyte hyphae that tend to be parallel to the surface.²

Pitted keratolysis is a superficial bacterial infection involving the soles of the feet. The classic clinical findings are shallow 1- to 2-mm pits in clusters that can coalesce on pressure-bearing areas. Hyperhidrosis, malodor, and maceration commonly are associated. Microscopic examination reveals clusters of small cocci and filamentous bacteria located in the dell or pit of a thick compact orthokeratotic stratum corneum of acral skin with no notable inflammatory infiltrate (Figure 2).² Special stains such as Gram, methenamine silver, or PAS can assist in visualization of the organisms. Pitted keratolysis is caused by Dermatophilus congolensis and Kytococcus sedentarius (formerly Micrococcus sedentarius), which produce keratinolytic enzymes causing the defect in the stratum corneum.³

Tinea cruris, also known as jock itch and ringworm of the groin, presents with advancing pruritic, circinate, erythematous, scaling patches with central clearing on the inner thighs and crural folds. Similar to tinea pedis, Trichophyton rubrum is the most common dermatophyte to cause tinea cruris.⁴ Potassium hydroxide preparation of skin scrapings from the advancing border show fungal hyphae that cross the keratin cell borders. The histopathology of dermatophyte infections can be subtle and resemble normal skin before close inspection of the stratum corneum, which can show compact orthokeratosis, neutrophils, or "sandwich sign" where hyphae are sandwiched between an upper basket weave layer and a lower compact cornified layer (orthokeratotic or parakeratotic)(Figure 3).¹ The presence of these patterns in the stratum corneum should result in performance of PAS to highlight obscure hyphae.

Tinea versicolor, also called pityriasis versicolor, usually presents with hypopigmented or less commonly hyperpigmented circular patches that coalesce on the upper trunk and shoulders. There is a fine fluffy scale that is most notable after scraping the skin for a potassium hydroxide preparation, which shows "spaghetti and meatballs" (hyphae and spores). Tinea versicolor typically is caused by the mycelial phase of the lipophilic yeast Malassezia globosae.³ Histologically, there are yeast and short septate hyphae scattered in a loose basket weave hyperkeratotic stratum corneum with minimal or no inflammation (Figure 4). On occasion, PAS is required for identification.

To the Editor:

A 68-year-old man presented with slightly itchy macules on the waist and abdomen of approximately 2 years’ duration. He reported that the initial lesions were dark red and subsequently coalesced to form a beltlike pigmentation on the abdomen. He denied any prior treatment, and the lesions did not spontaneously resolve. The patient was taking escitalopram oxalate, telmisartan, and aspirin for depression and cardiovascular disease that was diagnosed 3 years prior. He reported no exposure to UV radiation or a heat source. He denied use of any cosmetics on the body as well as a family history of similar symptoms.

Physical examination showed reticulate brown-purple macules with slight scale on the surface that had become confluent, forming a beltlike pigmentation on the waist and abdomen (Figure 1). Wickham striae were not seen. The oral mucosa and nails were not affected. Microscopic examination for fungal infections was negative.

Systematic physical and laboratory examinations revealed no abnormalities. A skin biopsy from a macule on the abdomen showed hyperkeratosis, thinned out stratum spinosum with flattening of rete ridges, hypergranulosis with vacuolar alteration of the basal cell layer, and bandlike infiltration of lymphocytes and melanophages with incontinence of pigment (Figure 2). Focalized purplish homogeneous deposits were observed in the upper dermis (Figure 3), of which positive crystal violet staining indicated amyloidosis (Figure 4). Congo red stain revealed amyloid deposition (Figure 5). Thus, the diagnosis of lichen planus pigmentosus (LPP) complicated with focal amyloidosis was made. The patient was treated with topical corticosteroids and tretinoin, and no notable therapeutic effects were observed at 3-month follow-up.

Lichen planus pigmentosus, a variant of lichen planus, is a condition of unknown etiology exhibiting dark brown macules and/or papules and a long clinical course. The face, neck, trunk, arms, and legs are the most common areas of presentation, whereas involvement of the scalp, nails, or oral mucosa is relatively rare.

The first clinicohistopathological study with a large sample size was documented by Bhutani et al¹ in 1974 who termed the currently recognized entity lichen planus pigmentosus. Lichen planus pigmentosus is a frequently encountered hyperpigmentation disorder in Indians, whereas sporadic cases also are reported in other regions and ethnicities.² In cases of LPP, the pigmentation is symmetrical, and its pattern most often is diffuse, then reticular, blotchy, and perifollicular.³ Two unique patterns of LPP have been documented, including linear/blaschkoid LPP and zosteriform LPP.^4,5 Our patient showed a unique beltlike distribution pattern.

The pathogenesis of LPP still is unclear, and several inciting factors such as mustard oil, gold therapy,⁶ and hepatitis C virus infection have been cited.⁷ Mancuso and Berdondini⁸ reported a case of LPP flaring immediately after relapse of nephrotic syndrome. It also has been considered as a paraneoplastic phenomen.⁹ No exact cause was found in our patient after a series of relative examinations.

The histopathologic changes associated with LPP consist of atrophic epidermis; bandlike lymphocytic infiltrate with vacuolar degeneration of the basal layer in the epidermis; and prominent melanin incontinence in the upper dermis, which can be diverse depending on different sites of skin biopsy and the phase of LPP. Histopathologic findings in our patient were consistent with LPP. The differential diagnosis for the reticulate pattern of pigmentation seen in our patient included confluent and reticulated papillomatosis and poikilodermalike cutaneous amyloidosis, both easily excluded with histopathologic confirmation.

Local amyloidosis also was confirmed by crystal violet staining in our case and its etiology was uncertain. Generalized and local amyloidosis has been reported in association with lichen planus. The diagnosis of lichen planus was followed by the diagnosis of amyloidosis, and the typical skin lesions of these 2 conditions were able to be differentiated in these reported cases.^10,11 However, beltlike pigmentation was the only manifestation for our patient and we could not separate the 2 conditions with the naked eye.

Chronic irritation to the skin resulting in excessive production of degenerate keratins and their subsequent conversion into amyloid deposits has been proposed to be an etiologic factor of amyloidosis.¹¹ Because of the distribution pattern in our case, we believe focal amyloidosis could be attributed to chronic friction and scratching.

To the Editor:

A 68-year-old man presented with slightly itchy macules on the waist and abdomen of approximately 2 years’ duration. He reported that the initial lesions were dark red and subsequently coalesced to form a beltlike pigmentation on the abdomen. He denied any prior treatment, and the lesions did not spontaneously resolve. The patient was taking escitalopram oxalate, telmisartan, and aspirin for depression and cardiovascular disease that was diagnosed 3 years prior. He reported no exposure to UV radiation or a heat source. He denied use of any cosmetics on the body as well as a family history of similar symptoms.

Physical examination showed reticulate brown-purple macules with slight scale on the surface that had become confluent, forming a beltlike pigmentation on the waist and abdomen (Figure 1). Wickham striae were not seen. The oral mucosa and nails were not affected. Microscopic examination for fungal infections was negative.

Systematic physical and laboratory examinations revealed no abnormalities. A skin biopsy from a macule on the abdomen showed hyperkeratosis, thinned out stratum spinosum with flattening of rete ridges, hypergranulosis with vacuolar alteration of the basal cell layer, and bandlike infiltration of lymphocytes and melanophages with incontinence of pigment (Figure 2). Focalized purplish homogeneous deposits were observed in the upper dermis (Figure 3), of which positive crystal violet staining indicated amyloidosis (Figure 4). Congo red stain revealed amyloid deposition (Figure 5). Thus, the diagnosis of lichen planus pigmentosus (LPP) complicated with focal amyloidosis was made. The patient was treated with topical corticosteroids and tretinoin, and no notable therapeutic effects were observed at 3-month follow-up.

Lichen planus pigmentosus, a variant of lichen planus, is a condition of unknown etiology exhibiting dark brown macules and/or papules and a long clinical course. The face, neck, trunk, arms, and legs are the most common areas of presentation, whereas involvement of the scalp, nails, or oral mucosa is relatively rare.

The first clinicohistopathological study with a large sample size was documented by Bhutani et al¹ in 1974 who termed the currently recognized entity lichen planus pigmentosus. Lichen planus pigmentosus is a frequently encountered hyperpigmentation disorder in Indians, whereas sporadic cases also are reported in other regions and ethnicities.² In cases of LPP, the pigmentation is symmetrical, and its pattern most often is diffuse, then reticular, blotchy, and perifollicular.³ Two unique patterns of LPP have been documented, including linear/blaschkoid LPP and zosteriform LPP.^4,5 Our patient showed a unique beltlike distribution pattern.

The pathogenesis of LPP still is unclear, and several inciting factors such as mustard oil, gold therapy,⁶ and hepatitis C virus infection have been cited.⁷ Mancuso and Berdondini⁸ reported a case of LPP flaring immediately after relapse of nephrotic syndrome. It also has been considered as a paraneoplastic phenomen.⁹ No exact cause was found in our patient after a series of relative examinations.

The histopathologic changes associated with LPP consist of atrophic epidermis; bandlike lymphocytic infiltrate with vacuolar degeneration of the basal layer in the epidermis; and prominent melanin incontinence in the upper dermis, which can be diverse depending on different sites of skin biopsy and the phase of LPP. Histopathologic findings in our patient were consistent with LPP. The differential diagnosis for the reticulate pattern of pigmentation seen in our patient included confluent and reticulated papillomatosis and poikilodermalike cutaneous amyloidosis, both easily excluded with histopathologic confirmation.

Local amyloidosis also was confirmed by crystal violet staining in our case and its etiology was uncertain. Generalized and local amyloidosis has been reported in association with lichen planus. The diagnosis of lichen planus was followed by the diagnosis of amyloidosis, and the typical skin lesions of these 2 conditions were able to be differentiated in these reported cases.^10,11 However, beltlike pigmentation was the only manifestation for our patient and we could not separate the 2 conditions with the naked eye.

Chronic irritation to the skin resulting in excessive production of degenerate keratins and their subsequent conversion into amyloid deposits has been proposed to be an etiologic factor of amyloidosis.¹¹ Because of the distribution pattern in our case, we believe focal amyloidosis could be attributed to chronic friction and scratching.

To the Editor:

A 68-year-old man presented with slightly itchy macules on the waist and abdomen of approximately 2 years’ duration. He reported that the initial lesions were dark red and subsequently coalesced to form a beltlike pigmentation on the abdomen. He denied any prior treatment, and the lesions did not spontaneously resolve. The patient was taking escitalopram oxalate, telmisartan, and aspirin for depression and cardiovascular disease that was diagnosed 3 years prior. He reported no exposure to UV radiation or a heat source. He denied use of any cosmetics on the body as well as a family history of similar symptoms.

Physical examination showed reticulate brown-purple macules with slight scale on the surface that had become confluent, forming a beltlike pigmentation on the waist and abdomen (Figure 1). Wickham striae were not seen. The oral mucosa and nails were not affected. Microscopic examination for fungal infections was negative.

Systematic physical and laboratory examinations revealed no abnormalities. A skin biopsy from a macule on the abdomen showed hyperkeratosis, thinned out stratum spinosum with flattening of rete ridges, hypergranulosis with vacuolar alteration of the basal cell layer, and bandlike infiltration of lymphocytes and melanophages with incontinence of pigment (Figure 2). Focalized purplish homogeneous deposits were observed in the upper dermis (Figure 3), of which positive crystal violet staining indicated amyloidosis (Figure 4). Congo red stain revealed amyloid deposition (Figure 5). Thus, the diagnosis of lichen planus pigmentosus (LPP) complicated with focal amyloidosis was made. The patient was treated with topical corticosteroids and tretinoin, and no notable therapeutic effects were observed at 3-month follow-up.

Lichen planus pigmentosus, a variant of lichen planus, is a condition of unknown etiology exhibiting dark brown macules and/or papules and a long clinical course. The face, neck, trunk, arms, and legs are the most common areas of presentation, whereas involvement of the scalp, nails, or oral mucosa is relatively rare.

The first clinicohistopathological study with a large sample size was documented by Bhutani et al¹ in 1974 who termed the currently recognized entity lichen planus pigmentosus. Lichen planus pigmentosus is a frequently encountered hyperpigmentation disorder in Indians, whereas sporadic cases also are reported in other regions and ethnicities.² In cases of LPP, the pigmentation is symmetrical, and its pattern most often is diffuse, then reticular, blotchy, and perifollicular.³ Two unique patterns of LPP have been documented, including linear/blaschkoid LPP and zosteriform LPP.^4,5 Our patient showed a unique beltlike distribution pattern.

The pathogenesis of LPP still is unclear, and several inciting factors such as mustard oil, gold therapy,⁶ and hepatitis C virus infection have been cited.⁷ Mancuso and Berdondini⁸ reported a case of LPP flaring immediately after relapse of nephrotic syndrome. It also has been considered as a paraneoplastic phenomen.⁹ No exact cause was found in our patient after a series of relative examinations.

The histopathologic changes associated with LPP consist of atrophic epidermis; bandlike lymphocytic infiltrate with vacuolar degeneration of the basal layer in the epidermis; and prominent melanin incontinence in the upper dermis, which can be diverse depending on different sites of skin biopsy and the phase of LPP. Histopathologic findings in our patient were consistent with LPP. The differential diagnosis for the reticulate pattern of pigmentation seen in our patient included confluent and reticulated papillomatosis and poikilodermalike cutaneous amyloidosis, both easily excluded with histopathologic confirmation.

Local amyloidosis also was confirmed by crystal violet staining in our case and its etiology was uncertain. Generalized and local amyloidosis has been reported in association with lichen planus. The diagnosis of lichen planus was followed by the diagnosis of amyloidosis, and the typical skin lesions of these 2 conditions were able to be differentiated in these reported cases.^10,11 However, beltlike pigmentation was the only manifestation for our patient and we could not separate the 2 conditions with the naked eye.

Chronic irritation to the skin resulting in excessive production of degenerate keratins and their subsequent conversion into amyloid deposits has been proposed to be an etiologic factor of amyloidosis.¹¹ Because of the distribution pattern in our case, we believe focal amyloidosis could be attributed to chronic friction and scratching.

To the Editor:

A 34-year-old woman presented with a generalized pustular eruption with subjective fevers, chills, night sweats, and light-headedness. Ten days prior to admission she developed a generalized erythematous and pruritic rash; she had started pantoprazole for reflux 4 days prior to the rash. On admission, skin examination revealed facial edema and diffuse erythema covering 80% of the total body surface area with multiple 1- to 4-mm pustules coalescing into lakes of pus on the trunk as well as bilateral upper and lower arms and legs sparing the palms and soles. Desquamation and serous drainage with crust were observed on the skin of the head, upper trunk, and thighs (Figure 1). Vital signs were notable for hypotension. Laboratory tests on admission were remarkable for leukocytosis (white blood cell count: 22.5×10³/μL [reference range, 4.5–11×10³/μL]) with absolute eosinophilia but no neutrophilia. C-reactive protein (CRP) was elevated (237.9 mg/L [reference range, 5.0–9.9 mg/L]). Renal and hepatic functions were normal. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). Further infectious disease workup for viral and fungal pathogens was negative.

Skin biopsy from the left thigh revealed subcorneal, pustular, acute spongiotic dermatitis with marked intraepidermal spongiosis and papillary edema; exocytosis of eosinophils; and single cell necrosis of keratinocytes (Figure 2). These findings were consistent with acute generalized exanthematous pustulosis (AGEP). Pantoprazole was discontinued, and cardiovascular support and antibiotic therapy for MSSA bacteremia were initiated. Respiratory, kidney, and liver functions remained normal throughout the 11-day hospitalization, and the pustular dermatitis, MSSA bacteremia, and cardiovascular symptoms resolved within 10 days.

Acute generalized exanthematous pustulosis is an uncommon, self-limited, generalized sterile pustular eruption notable for the usual absence of systemic symptoms and extracutaneous organ involvement. Hotz et al¹ found that mean peripheral neutrophil counts (mean, 21.5×10³/μL) and CRP levels (mean, 241.6 mg/L) were notably elevated in patients with systemic (ie, hepatic, pulmonary, renal, bone marrow) involvement. In our patient, only the CRP approached the elevated value reported by Hotz et al.¹ However, the patient exhibited only cardiovascular instability in the context of secondary bacteremia and no other systemic symptoms. The combination of highly elevated neutrophilia and CRP may be a better marker for AGEP-precipitated extracutaneous organ involvement.

Although infectious pathogens such as Epstein-Barr virus and cytomegalovirus have been implicated, the majority of AGEP cases are adverse reactions (ARs) to medications, such as β-lactam antibiotics. In our patient, the widely prescribed proton pump inhibitor (PPI) pantoprazole was the most likely cause. Acute generalized exanthematous pustulosis was reported in a patient taking another PPI, omeprazole.² However, PPIs are recognized to cause many cutaneous and other organ ARs, though prevalence of ARs is still low. In Thailand, Chularojanamontri et al³ reported 13.8 per 100,000 individuals developed a cutaneous AR to PPIs, and the ARs most frequently were attributed to omeprazole. They found that drug exanthems were the most common cutaneous ARs.³ However, more severe hypersensitivity reactions have been reported, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and autoimmune eruptions such as cutaneous lupus erythematosus.^3,4 Other systemic reactions to PPIs include increased risks for urticaria, pneumonia, Clostridium difficile infections, and acute interstitial nephritis.^4,5

To the Editor:

A 34-year-old woman presented with a generalized pustular eruption with subjective fevers, chills, night sweats, and light-headedness. Ten days prior to admission she developed a generalized erythematous and pruritic rash; she had started pantoprazole for reflux 4 days prior to the rash. On admission, skin examination revealed facial edema and diffuse erythema covering 80% of the total body surface area with multiple 1- to 4-mm pustules coalescing into lakes of pus on the trunk as well as bilateral upper and lower arms and legs sparing the palms and soles. Desquamation and serous drainage with crust were observed on the skin of the head, upper trunk, and thighs (Figure 1). Vital signs were notable for hypotension. Laboratory tests on admission were remarkable for leukocytosis (white blood cell count: 22.5×10³/μL [reference range, 4.5–11×10³/μL]) with absolute eosinophilia but no neutrophilia. C-reactive protein (CRP) was elevated (237.9 mg/L [reference range, 5.0–9.9 mg/L]). Renal and hepatic functions were normal. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). Further infectious disease workup for viral and fungal pathogens was negative.

Skin biopsy from the left thigh revealed subcorneal, pustular, acute spongiotic dermatitis with marked intraepidermal spongiosis and papillary edema; exocytosis of eosinophils; and single cell necrosis of keratinocytes (Figure 2). These findings were consistent with acute generalized exanthematous pustulosis (AGEP). Pantoprazole was discontinued, and cardiovascular support and antibiotic therapy for MSSA bacteremia were initiated. Respiratory, kidney, and liver functions remained normal throughout the 11-day hospitalization, and the pustular dermatitis, MSSA bacteremia, and cardiovascular symptoms resolved within 10 days.

Acute generalized exanthematous pustulosis is an uncommon, self-limited, generalized sterile pustular eruption notable for the usual absence of systemic symptoms and extracutaneous organ involvement. Hotz et al¹ found that mean peripheral neutrophil counts (mean, 21.5×10³/μL) and CRP levels (mean, 241.6 mg/L) were notably elevated in patients with systemic (ie, hepatic, pulmonary, renal, bone marrow) involvement. In our patient, only the CRP approached the elevated value reported by Hotz et al.¹ However, the patient exhibited only cardiovascular instability in the context of secondary bacteremia and no other systemic symptoms. The combination of highly elevated neutrophilia and CRP may be a better marker for AGEP-precipitated extracutaneous organ involvement.

Although infectious pathogens such as Epstein-Barr virus and cytomegalovirus have been implicated, the majority of AGEP cases are adverse reactions (ARs) to medications, such as β-lactam antibiotics. In our patient, the widely prescribed proton pump inhibitor (PPI) pantoprazole was the most likely cause. Acute generalized exanthematous pustulosis was reported in a patient taking another PPI, omeprazole.² However, PPIs are recognized to cause many cutaneous and other organ ARs, though prevalence of ARs is still low. In Thailand, Chularojanamontri et al³ reported 13.8 per 100,000 individuals developed a cutaneous AR to PPIs, and the ARs most frequently were attributed to omeprazole. They found that drug exanthems were the most common cutaneous ARs.³ However, more severe hypersensitivity reactions have been reported, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and autoimmune eruptions such as cutaneous lupus erythematosus.^3,4 Other systemic reactions to PPIs include increased risks for urticaria, pneumonia, Clostridium difficile infections, and acute interstitial nephritis.^4,5

To the Editor:

A 34-year-old woman presented with a generalized pustular eruption with subjective fevers, chills, night sweats, and light-headedness. Ten days prior to admission she developed a generalized erythematous and pruritic rash; she had started pantoprazole for reflux 4 days prior to the rash. On admission, skin examination revealed facial edema and diffuse erythema covering 80% of the total body surface area with multiple 1- to 4-mm pustules coalescing into lakes of pus on the trunk as well as bilateral upper and lower arms and legs sparing the palms and soles. Desquamation and serous drainage with crust were observed on the skin of the head, upper trunk, and thighs (Figure 1). Vital signs were notable for hypotension. Laboratory tests on admission were remarkable for leukocytosis (white blood cell count: 22.5×10³/μL [reference range, 4.5–11×10³/μL]) with absolute eosinophilia but no neutrophilia. C-reactive protein (CRP) was elevated (237.9 mg/L [reference range, 5.0–9.9 mg/L]). Renal and hepatic functions were normal. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). Further infectious disease workup for viral and fungal pathogens was negative.

Skin biopsy from the left thigh revealed subcorneal, pustular, acute spongiotic dermatitis with marked intraepidermal spongiosis and papillary edema; exocytosis of eosinophils; and single cell necrosis of keratinocytes (Figure 2). These findings were consistent with acute generalized exanthematous pustulosis (AGEP). Pantoprazole was discontinued, and cardiovascular support and antibiotic therapy for MSSA bacteremia were initiated. Respiratory, kidney, and liver functions remained normal throughout the 11-day hospitalization, and the pustular dermatitis, MSSA bacteremia, and cardiovascular symptoms resolved within 10 days.

Acute generalized exanthematous pustulosis is an uncommon, self-limited, generalized sterile pustular eruption notable for the usual absence of systemic symptoms and extracutaneous organ involvement. Hotz et al¹ found that mean peripheral neutrophil counts (mean, 21.5×10³/μL) and CRP levels (mean, 241.6 mg/L) were notably elevated in patients with systemic (ie, hepatic, pulmonary, renal, bone marrow) involvement. In our patient, only the CRP approached the elevated value reported by Hotz et al.¹ However, the patient exhibited only cardiovascular instability in the context of secondary bacteremia and no other systemic symptoms. The combination of highly elevated neutrophilia and CRP may be a better marker for AGEP-precipitated extracutaneous organ involvement.

Although infectious pathogens such as Epstein-Barr virus and cytomegalovirus have been implicated, the majority of AGEP cases are adverse reactions (ARs) to medications, such as β-lactam antibiotics. In our patient, the widely prescribed proton pump inhibitor (PPI) pantoprazole was the most likely cause. Acute generalized exanthematous pustulosis was reported in a patient taking another PPI, omeprazole.² However, PPIs are recognized to cause many cutaneous and other organ ARs, though prevalence of ARs is still low. In Thailand, Chularojanamontri et al³ reported 13.8 per 100,000 individuals developed a cutaneous AR to PPIs, and the ARs most frequently were attributed to omeprazole. They found that drug exanthems were the most common cutaneous ARs.³ However, more severe hypersensitivity reactions have been reported, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and autoimmune eruptions such as cutaneous lupus erythematosus.^3,4 Other systemic reactions to PPIs include increased risks for urticaria, pneumonia, Clostridium difficile infections, and acute interstitial nephritis.^4,5

To the Editor:

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare disorder that often is associated with systemic disease. It has been shown to manifest in the presence of systemic lupus erythematosus; rheumatoid arthritis; Wegener granulomatosis; and other diseases, mainly autoimmune conditions. Interstitial granulomatous dermatitis (IGD) associated with arthritis was first described by Ackerman et al¹ in 1993. In 1994, IGD was placed among the spectrum of PNGD by Chu et al.² The disease entities included in the spectrum of PNGD of the immune complex disease are Churg-Strauss granuloma, cutaneous extravascular necrotizing granuloma, rheumatoid papules, superficial ulcerating rheumatoid necrobiosis, and IGD with arthritis.² It has been suggested that IGD has a distinct clinical presentation with associated histopathology, while others suggest it still is part of the PNGD spectrum.^2,3 We present 2 cases of granulomatous dermatitis and their findings related to IGD and PNGD.

A 58-year-old woman presented with recurrent painful lesions on the trunk, arms, and legs of 2 years’ duration. The lesions spontaneously resolved without scarring or hyperpigmentation but would recur in different areas on the trunk. She was diagnosed with rheumatoid arthritis following a recent autoimmune workup. At presentation, physical examination revealed tender erythematous edematous plaques on the bilateral upper back (Figure 1) and erythematous nodules on the bilateral upper arms. The patient previously had an antinuclear antibody titer of 1:320 with a speckled pattern. A repeat antinuclear antibody titer taken 1 year later was negative. Her rheumatoid factor initially was positive and remained positive upon repeat testing. Punch biopsies were performed for histologic evaluation of the lesions and immunofluorescence. Biopsies examined with hematoxylin and eosin stain revealed perivascular and interstitial mixed (lymphocytic, neutrophilic, eosinophilic) bottom-heavy inflammation with nuclear dust and basophilic degeneration of collagen (Figure 2). Immunofluorescence studies were negative. The patient deferred treatment.

A 74-year-old man presented with a rash on the flank and back with associated pruritus and occasional pain of 2 months’ duration. His primary care physician prescribed a course of cephalexin, but the rash did not improve. Review of systems was positive for intermittent swelling of the hands, feet, and lips, and negative for arthritis. His medical history included 2 episodes of rheumatic fever, one complicated by pneumonia. His medications included finasteride, simvastatin, bisoprolol-hydrochlorothiazide, aspirin, tiotropium, vitamin D, and fish oil. At presentation, physical examination revealed tender violaceous plaques with induration and central clearing distributed on the left side of the back, left side of the flank, and left axilla. The lesion on the axilla measured 30.0×3.5 cm and the lesions on the left side of the back measured 30.0×9.0 cm. The rims of the lesions were elevated and consistent with the rope sign (Figure 3). A punch biopsy of the lesion on the left axilla showed perivascular and interstitial infiltrate of lymphocytes, neutrophils, histiocytes, and eosinophils. There was no evidence of fibrin deposition in the blood vessels. Small areas of necrobiotic collagen surrounded by multinucleated giant cells and lymphocytes were noted (Figure 4). The rash improved spontaneously at the time of suture removal. No treatment was initiated.

Granulomatous dermatitis in the presence of an autoimmune disorder can present as IGD or PNGD. Both forms of granulomatous dermatitis are rare conditions and considered to be part of the same clinicopathological spectrum. These conditions can be difficult to distinguish clinically but are histologically unique.

Interstitial granulomatous dermatitis and PNGD can have a variable clinical expression. Palisaded neutrophilic granulomatous dermatitis generally presents as flesh-colored to erythematous papules or plaques, most commonly located on the upper arms. The lesions may have a central umbilication with perforation and ulceration.⁴ Interstitial granulomatous dermatitis most commonly presents as erythematous plaques and papules. The lesions are symmetric and asymptomatic. They most commonly appear on the trunk, axillae, buttocks, thighs, and groin. Subcutaneous linear cords (the rope sign) is a characteristic associated with IGD.^3,5 However, the rope sign also has been reported in a patient with PNGD with systemic lupus,⁶ which further demonstrates the overlapping spectrum of clinical expression seen in these 2 forms of granulomatous dermatitis. Therefore, a diagnosis cannot be made by clinical expression alone; histologic findings are needed for confirmation.

When differentiating IGD and PNGD histologically, it is important to keep in mind that these features exist on a spectrum and depend on the age of the lesion. Deposition of the immune complex around the dermal blood vessel initiates the pathogenesis. Early lesions of PNGD show a neutrophilic infiltrate, focal leukocytoclastic vasculitis, and dense nuclear dust. Developed lesions show zones of basophilic degenerated collagen surrounded by palisades of histiocytes, neutrophils, and nuclear debris.² The histologic pattern of IGD features smaller areas of palisading histiocytes surrounding foci of degenerated collagen. Neutrophils and eosinophils are seen among the degenerated collagen. There is no evidence of vasculitis and dermal mucin usually is absent.⁷

Palisaded neutrophilic granulomatous dermatitis has been reported to improve with systemic steroids and dapsone.⁸ The lesions may resolve spontaneously and with treatment of the underlying systemic disease. Similarly, IGD has been reported to resolve with systemic or topical steroids.^3,5 The rash in our patient with IGD (patient 2) spontaneously resolved. Our patient with PNGD (patient 1) reported that her lesions would spontaneously resolve, then recur. She had deferred all other treatment.

Some authors have disputed the spectrum that Chu et al² had determined in their study and proposed IGD is a separate entity from the PNGD spectrum. Verneuil et al⁹ stated that the clinical presentations in Chu et al’s² study (symmetric papules of the extremities) had not been reported in a patient with IGD. However, in a study of IGD by Peroni et al,³ 7 of 12 patients presented with symmetrical papules of the extremities. We believe that the spectrum proposed by Chu et al² still holds true.

These 2 reports demonstrate the diverse presentation of IGD and PNGD. It is important for dermatologists to keep in mind the PNGD spectrum when a patient presents with granulomatous dermatitis in the presence of an autoimmune disorder.

To the Editor:

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare disorder that often is associated with systemic disease. It has been shown to manifest in the presence of systemic lupus erythematosus; rheumatoid arthritis; Wegener granulomatosis; and other diseases, mainly autoimmune conditions. Interstitial granulomatous dermatitis (IGD) associated with arthritis was first described by Ackerman et al¹ in 1993. In 1994, IGD was placed among the spectrum of PNGD by Chu et al.² The disease entities included in the spectrum of PNGD of the immune complex disease are Churg-Strauss granuloma, cutaneous extravascular necrotizing granuloma, rheumatoid papules, superficial ulcerating rheumatoid necrobiosis, and IGD with arthritis.² It has been suggested that IGD has a distinct clinical presentation with associated histopathology, while others suggest it still is part of the PNGD spectrum.^2,3 We present 2 cases of granulomatous dermatitis and their findings related to IGD and PNGD.

A 58-year-old woman presented with recurrent painful lesions on the trunk, arms, and legs of 2 years’ duration. The lesions spontaneously resolved without scarring or hyperpigmentation but would recur in different areas on the trunk. She was diagnosed with rheumatoid arthritis following a recent autoimmune workup. At presentation, physical examination revealed tender erythematous edematous plaques on the bilateral upper back (Figure 1) and erythematous nodules on the bilateral upper arms. The patient previously had an antinuclear antibody titer of 1:320 with a speckled pattern. A repeat antinuclear antibody titer taken 1 year later was negative. Her rheumatoid factor initially was positive and remained positive upon repeat testing. Punch biopsies were performed for histologic evaluation of the lesions and immunofluorescence. Biopsies examined with hematoxylin and eosin stain revealed perivascular and interstitial mixed (lymphocytic, neutrophilic, eosinophilic) bottom-heavy inflammation with nuclear dust and basophilic degeneration of collagen (Figure 2). Immunofluorescence studies were negative. The patient deferred treatment.

A 74-year-old man presented with a rash on the flank and back with associated pruritus and occasional pain of 2 months’ duration. His primary care physician prescribed a course of cephalexin, but the rash did not improve. Review of systems was positive for intermittent swelling of the hands, feet, and lips, and negative for arthritis. His medical history included 2 episodes of rheumatic fever, one complicated by pneumonia. His medications included finasteride, simvastatin, bisoprolol-hydrochlorothiazide, aspirin, tiotropium, vitamin D, and fish oil. At presentation, physical examination revealed tender violaceous plaques with induration and central clearing distributed on the left side of the back, left side of the flank, and left axilla. The lesion on the axilla measured 30.0×3.5 cm and the lesions on the left side of the back measured 30.0×9.0 cm. The rims of the lesions were elevated and consistent with the rope sign (Figure 3). A punch biopsy of the lesion on the left axilla showed perivascular and interstitial infiltrate of lymphocytes, neutrophils, histiocytes, and eosinophils. There was no evidence of fibrin deposition in the blood vessels. Small areas of necrobiotic collagen surrounded by multinucleated giant cells and lymphocytes were noted (Figure 4). The rash improved spontaneously at the time of suture removal. No treatment was initiated.

Granulomatous dermatitis in the presence of an autoimmune disorder can present as IGD or PNGD. Both forms of granulomatous dermatitis are rare conditions and considered to be part of the same clinicopathological spectrum. These conditions can be difficult to distinguish clinically but are histologically unique.

Interstitial granulomatous dermatitis and PNGD can have a variable clinical expression. Palisaded neutrophilic granulomatous dermatitis generally presents as flesh-colored to erythematous papules or plaques, most commonly located on the upper arms. The lesions may have a central umbilication with perforation and ulceration.⁴ Interstitial granulomatous dermatitis most commonly presents as erythematous plaques and papules. The lesions are symmetric and asymptomatic. They most commonly appear on the trunk, axillae, buttocks, thighs, and groin. Subcutaneous linear cords (the rope sign) is a characteristic associated with IGD.^3,5 However, the rope sign also has been reported in a patient with PNGD with systemic lupus,⁶ which further demonstrates the overlapping spectrum of clinical expression seen in these 2 forms of granulomatous dermatitis. Therefore, a diagnosis cannot be made by clinical expression alone; histologic findings are needed for confirmation.

When differentiating IGD and PNGD histologically, it is important to keep in mind that these features exist on a spectrum and depend on the age of the lesion. Deposition of the immune complex around the dermal blood vessel initiates the pathogenesis. Early lesions of PNGD show a neutrophilic infiltrate, focal leukocytoclastic vasculitis, and dense nuclear dust. Developed lesions show zones of basophilic degenerated collagen surrounded by palisades of histiocytes, neutrophils, and nuclear debris.² The histologic pattern of IGD features smaller areas of palisading histiocytes surrounding foci of degenerated collagen. Neutrophils and eosinophils are seen among the degenerated collagen. There is no evidence of vasculitis and dermal mucin usually is absent.⁷

Palisaded neutrophilic granulomatous dermatitis has been reported to improve with systemic steroids and dapsone.⁸ The lesions may resolve spontaneously and with treatment of the underlying systemic disease. Similarly, IGD has been reported to resolve with systemic or topical steroids.^3,5 The rash in our patient with IGD (patient 2) spontaneously resolved. Our patient with PNGD (patient 1) reported that her lesions would spontaneously resolve, then recur. She had deferred all other treatment.

Some authors have disputed the spectrum that Chu et al² had determined in their study and proposed IGD is a separate entity from the PNGD spectrum. Verneuil et al⁹ stated that the clinical presentations in Chu et al’s² study (symmetric papules of the extremities) had not been reported in a patient with IGD. However, in a study of IGD by Peroni et al,³ 7 of 12 patients presented with symmetrical papules of the extremities. We believe that the spectrum proposed by Chu et al² still holds true.

These 2 reports demonstrate the diverse presentation of IGD and PNGD. It is important for dermatologists to keep in mind the PNGD spectrum when a patient presents with granulomatous dermatitis in the presence of an autoimmune disorder.

To the Editor:

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare disorder that often is associated with systemic disease. It has been shown to manifest in the presence of systemic lupus erythematosus; rheumatoid arthritis; Wegener granulomatosis; and other diseases, mainly autoimmune conditions. Interstitial granulomatous dermatitis (IGD) associated with arthritis was first described by Ackerman et al¹ in 1993. In 1994, IGD was placed among the spectrum of PNGD by Chu et al.² The disease entities included in the spectrum of PNGD of the immune complex disease are Churg-Strauss granuloma, cutaneous extravascular necrotizing granuloma, rheumatoid papules, superficial ulcerating rheumatoid necrobiosis, and IGD with arthritis.² It has been suggested that IGD has a distinct clinical presentation with associated histopathology, while others suggest it still is part of the PNGD spectrum.^2,3 We present 2 cases of granulomatous dermatitis and their findings related to IGD and PNGD.

A 58-year-old woman presented with recurrent painful lesions on the trunk, arms, and legs of 2 years’ duration. The lesions spontaneously resolved without scarring or hyperpigmentation but would recur in different areas on the trunk. She was diagnosed with rheumatoid arthritis following a recent autoimmune workup. At presentation, physical examination revealed tender erythematous edematous plaques on the bilateral upper back (Figure 1) and erythematous nodules on the bilateral upper arms. The patient previously had an antinuclear antibody titer of 1:320 with a speckled pattern. A repeat antinuclear antibody titer taken 1 year later was negative. Her rheumatoid factor initially was positive and remained positive upon repeat testing. Punch biopsies were performed for histologic evaluation of the lesions and immunofluorescence. Biopsies examined with hematoxylin and eosin stain revealed perivascular and interstitial mixed (lymphocytic, neutrophilic, eosinophilic) bottom-heavy inflammation with nuclear dust and basophilic degeneration of collagen (Figure 2). Immunofluorescence studies were negative. The patient deferred treatment.

A 74-year-old man presented with a rash on the flank and back with associated pruritus and occasional pain of 2 months’ duration. His primary care physician prescribed a course of cephalexin, but the rash did not improve. Review of systems was positive for intermittent swelling of the hands, feet, and lips, and negative for arthritis. His medical history included 2 episodes of rheumatic fever, one complicated by pneumonia. His medications included finasteride, simvastatin, bisoprolol-hydrochlorothiazide, aspirin, tiotropium, vitamin D, and fish oil. At presentation, physical examination revealed tender violaceous plaques with induration and central clearing distributed on the left side of the back, left side of the flank, and left axilla. The lesion on the axilla measured 30.0×3.5 cm and the lesions on the left side of the back measured 30.0×9.0 cm. The rims of the lesions were elevated and consistent with the rope sign (Figure 3). A punch biopsy of the lesion on the left axilla showed perivascular and interstitial infiltrate of lymphocytes, neutrophils, histiocytes, and eosinophils. There was no evidence of fibrin deposition in the blood vessels. Small areas of necrobiotic collagen surrounded by multinucleated giant cells and lymphocytes were noted (Figure 4). The rash improved spontaneously at the time of suture removal. No treatment was initiated.

Granulomatous dermatitis in the presence of an autoimmune disorder can present as IGD or PNGD. Both forms of granulomatous dermatitis are rare conditions and considered to be part of the same clinicopathological spectrum. These conditions can be difficult to distinguish clinically but are histologically unique.

Interstitial granulomatous dermatitis and PNGD can have a variable clinical expression. Palisaded neutrophilic granulomatous dermatitis generally presents as flesh-colored to erythematous papules or plaques, most commonly located on the upper arms. The lesions may have a central umbilication with perforation and ulceration.⁴ Interstitial granulomatous dermatitis most commonly presents as erythematous plaques and papules. The lesions are symmetric and asymptomatic. They most commonly appear on the trunk, axillae, buttocks, thighs, and groin. Subcutaneous linear cords (the rope sign) is a characteristic associated with IGD.^3,5 However, the rope sign also has been reported in a patient with PNGD with systemic lupus,⁶ which further demonstrates the overlapping spectrum of clinical expression seen in these 2 forms of granulomatous dermatitis. Therefore, a diagnosis cannot be made by clinical expression alone; histologic findings are needed for confirmation.

When differentiating IGD and PNGD histologically, it is important to keep in mind that these features exist on a spectrum and depend on the age of the lesion. Deposition of the immune complex around the dermal blood vessel initiates the pathogenesis. Early lesions of PNGD show a neutrophilic infiltrate, focal leukocytoclastic vasculitis, and dense nuclear dust. Developed lesions show zones of basophilic degenerated collagen surrounded by palisades of histiocytes, neutrophils, and nuclear debris.² The histologic pattern of IGD features smaller areas of palisading histiocytes surrounding foci of degenerated collagen. Neutrophils and eosinophils are seen among the degenerated collagen. There is no evidence of vasculitis and dermal mucin usually is absent.⁷

Palisaded neutrophilic granulomatous dermatitis has been reported to improve with systemic steroids and dapsone.⁸ The lesions may resolve spontaneously and with treatment of the underlying systemic disease. Similarly, IGD has been reported to resolve with systemic or topical steroids.^3,5 The rash in our patient with IGD (patient 2) spontaneously resolved. Our patient with PNGD (patient 1) reported that her lesions would spontaneously resolve, then recur. She had deferred all other treatment.

Some authors have disputed the spectrum that Chu et al² had determined in their study and proposed IGD is a separate entity from the PNGD spectrum. Verneuil et al⁹ stated that the clinical presentations in Chu et al’s² study (symmetric papules of the extremities) had not been reported in a patient with IGD. However, in a study of IGD by Peroni et al,³ 7 of 12 patients presented with symmetrical papules of the extremities. We believe that the spectrum proposed by Chu et al² still holds true.

These 2 reports demonstrate the diverse presentation of IGD and PNGD. It is important for dermatologists to keep in mind the PNGD spectrum when a patient presents with granulomatous dermatitis in the presence of an autoimmune disorder.

To the Editor:

Angiokeratoma is a benign vascular tumor characterized by several dilated vessels in the superficial dermis accompanied by epidermal hyperplasia and hyperkeratosis.¹ Angiokeratoma of the vulva is a rare clinical finding, usually involving multiple lesions as part of the Fordyce type.² Solitary angiokeratoma occurs predominantly on the lower legs,³ and although other locations have been described, the presence of a solitary angiokeratoma on the vulva is rare.⁴ We report 2 cases of solitary angiokeratoma on the vulva that was misdiagnosed as malignant melanoma. Both patients were referred to our center for evaluation and excision.

A 65-year-old woman (patient 1) and a 67-year-old woman (patient 2) presented with a bluish black, growing, asymptomatic lesion on the right (Figure 1) and left labia majora, respectively. Both patients were referred by outside physicians for excision because of suspected malignant melanoma. Physical examinations revealed bluish black globular nodules that measured 0.5 and 0.3 cm in diameter, respectively. Dermoscopy (patient 1) revealed dark lacunae. Histopathologic examination of the vulvar lesion (patient 2) showed dilated, blood-filled, vascular spaces in the papillary dermis, accompanied by overlying acanthosis, hyperkeratosis, and papillomatosis that was consistent with angiokeratoma (Figure 2).

Angiokeratoma, particularly the solitary type, often is misdiagnosed. Clinical differential diagnoses may include a wide range of pathologic conditions, including condyloma acuminata, basal cell carcinoma, pyogenic granuloma, lymphangioma, nevi, condyloma lata, nodular prurigo, seborrheic keratosis, granuloma inguinale, and deep fungal infection.^2,5 However, due to its quickly growing nature and its dark complexion, malignant melanoma often is initially diagnosed. Because patients affected by angiokeratoma of the vulva usually are aged 20 to 40 years,⁵ and vulvar melanoma is typical for middle-aged women (median age, 68 years),⁶ this misdiagnosis is more likely in older patients. It should be noted that a high index of suspicion for melanoma often is present when examining the vulva, considering that this area is difficult to monitor, and there is an especially poor prognosis of vulvar melanoma due to its late detection.^6,7

In the past, biopsy was considered mandatory for confirming the diagnosis of vulvar angiokeratoma.^5,8,9 However, dermoscopy has emerged as a valuable tool for diagnosis of angiokeratoma¹⁰ and also was helpful as a diagnostic aid in one of our patients (patient 1). Therefore, we believe that dermoscopy should be performed prior to a biopsy of angiokeratomas of the vulva.

To the Editor:

Angiokeratoma is a benign vascular tumor characterized by several dilated vessels in the superficial dermis accompanied by epidermal hyperplasia and hyperkeratosis.¹ Angiokeratoma of the vulva is a rare clinical finding, usually involving multiple lesions as part of the Fordyce type.² Solitary angiokeratoma occurs predominantly on the lower legs,³ and although other locations have been described, the presence of a solitary angiokeratoma on the vulva is rare.⁴ We report 2 cases of solitary angiokeratoma on the vulva that was misdiagnosed as malignant melanoma. Both patients were referred to our center for evaluation and excision.

A 65-year-old woman (patient 1) and a 67-year-old woman (patient 2) presented with a bluish black, growing, asymptomatic lesion on the right (Figure 1) and left labia majora, respectively. Both patients were referred by outside physicians for excision because of suspected malignant melanoma. Physical examinations revealed bluish black globular nodules that measured 0.5 and 0.3 cm in diameter, respectively. Dermoscopy (patient 1) revealed dark lacunae. Histopathologic examination of the vulvar lesion (patient 2) showed dilated, blood-filled, vascular spaces in the papillary dermis, accompanied by overlying acanthosis, hyperkeratosis, and papillomatosis that was consistent with angiokeratoma (Figure 2).

Angiokeratoma, particularly the solitary type, often is misdiagnosed. Clinical differential diagnoses may include a wide range of pathologic conditions, including condyloma acuminata, basal cell carcinoma, pyogenic granuloma, lymphangioma, nevi, condyloma lata, nodular prurigo, seborrheic keratosis, granuloma inguinale, and deep fungal infection.^2,5 However, due to its quickly growing nature and its dark complexion, malignant melanoma often is initially diagnosed. Because patients affected by angiokeratoma of the vulva usually are aged 20 to 40 years,⁵ and vulvar melanoma is typical for middle-aged women (median age, 68 years),⁶ this misdiagnosis is more likely in older patients. It should be noted that a high index of suspicion for melanoma often is present when examining the vulva, considering that this area is difficult to monitor, and there is an especially poor prognosis of vulvar melanoma due to its late detection.^6,7

In the past, biopsy was considered mandatory for confirming the diagnosis of vulvar angiokeratoma.^5,8,9 However, dermoscopy has emerged as a valuable tool for diagnosis of angiokeratoma¹⁰ and also was helpful as a diagnostic aid in one of our patients (patient 1). Therefore, we believe that dermoscopy should be performed prior to a biopsy of angiokeratomas of the vulva.

To the Editor:

Angiokeratoma is a benign vascular tumor characterized by several dilated vessels in the superficial dermis accompanied by epidermal hyperplasia and hyperkeratosis.¹ Angiokeratoma of the vulva is a rare clinical finding, usually involving multiple lesions as part of the Fordyce type.² Solitary angiokeratoma occurs predominantly on the lower legs,³ and although other locations have been described, the presence of a solitary angiokeratoma on the vulva is rare.⁴ We report 2 cases of solitary angiokeratoma on the vulva that was misdiagnosed as malignant melanoma. Both patients were referred to our center for evaluation and excision.

A 65-year-old woman (patient 1) and a 67-year-old woman (patient 2) presented with a bluish black, growing, asymptomatic lesion on the right (Figure 1) and left labia majora, respectively. Both patients were referred by outside physicians for excision because of suspected malignant melanoma. Physical examinations revealed bluish black globular nodules that measured 0.5 and 0.3 cm in diameter, respectively. Dermoscopy (patient 1) revealed dark lacunae. Histopathologic examination of the vulvar lesion (patient 2) showed dilated, blood-filled, vascular spaces in the papillary dermis, accompanied by overlying acanthosis, hyperkeratosis, and papillomatosis that was consistent with angiokeratoma (Figure 2).

Angiokeratoma, particularly the solitary type, often is misdiagnosed. Clinical differential diagnoses may include a wide range of pathologic conditions, including condyloma acuminata, basal cell carcinoma, pyogenic granuloma, lymphangioma, nevi, condyloma lata, nodular prurigo, seborrheic keratosis, granuloma inguinale, and deep fungal infection.^2,5 However, due to its quickly growing nature and its dark complexion, malignant melanoma often is initially diagnosed. Because patients affected by angiokeratoma of the vulva usually are aged 20 to 40 years,⁵ and vulvar melanoma is typical for middle-aged women (median age, 68 years),⁶ this misdiagnosis is more likely in older patients. It should be noted that a high index of suspicion for melanoma often is present when examining the vulva, considering that this area is difficult to monitor, and there is an especially poor prognosis of vulvar melanoma due to its late detection.^6,7

In the past, biopsy was considered mandatory for confirming the diagnosis of vulvar angiokeratoma.^5,8,9 However, dermoscopy has emerged as a valuable tool for diagnosis of angiokeratoma¹⁰ and also was helpful as a diagnostic aid in one of our patients (patient 1). Therefore, we believe that dermoscopy should be performed prior to a biopsy of angiokeratomas of the vulva.

SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.

In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.

After examining her skin, Dr. Femia became immediately concerned.

“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.

These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.

“That is a form of dermatomyositis that you cannot miss,” she said.

The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.

Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.

“We want to treat these patients aggressively in order to avoid this.”

SOURCE: Femia A. CCR 2018.

SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.

In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.

After examining her skin, Dr. Femia became immediately concerned.

“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.

These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.

“That is a form of dermatomyositis that you cannot miss,” she said.

The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.

Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.

“We want to treat these patients aggressively in order to avoid this.”

SOURCE: Femia A. CCR 2018.

SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.

In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.

After examining her skin, Dr. Femia became immediately concerned.

“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.

These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.

“That is a form of dermatomyositis that you cannot miss,” she said.

The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.

Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.

“We want to treat these patients aggressively in order to avoid this.”

SOURCE: Femia A. CCR 2018.

The Diagnosis: Cutaneous Collagenous Vasculopathy

Histopathologic examination revealed ectatic blood vessels lined with unremarkable endothelial cells and thickened, hyalinized vessel walls scattered within the papillary dermis (Figure 1). The epidermis was unremarkable. There was minimal associated inflammation and no extravasation of erythrocytes. The hyalinized material was weakly positive on periodic acid-Schiff staining (Figure 2) and negative on Congo red staining, which supported of a diagnosis of cutaneous collagenous vasculopathy (CCV).

The patient previously had been given a suspected diagnosis of generalized essential telangiectasia by an outside dermatologist several years prior to the current presentation, as CCV had yet to be recognized as its own entity and therefore few cases had been described in the literature. She had a known history of obesity, hypertension, hyperlipidemia, and type 2 diabetes mellitus, which are associated with the condition. Multiple specialists concluded that the disease was too extensive for laser treatment. A review of PubMed articles indexed for MEDLINE yielded no established treatment options.

Cutaneous collagenous vasculopathy is a rare acquired microangiopathy involving the small vessels of the skin. Its clinical presentation is indistinguishable from that of generalized essential telangiectasia (GET). Patients generally present with asymptomatic, widespread, blanching, symmetric telangiectasias that classically begin on the legs and steadily progress upward with classic sparing of the face (Figure 3). Whereas GET has been reported to involve the oral and conjunctival mucosa, mucosal involvement is not typically observed in CCV and is considered to be a distinguishing factor between the 2 conditions.^1,2 However, our patient reported oral symptoms, and oral erosions were seen on multiple physical examinations; therefore, ours is a rare case of mucosal involvement in conjunction with CCV. Given this finding, it is possible that more cases of CCV with mucosal involvement may exist but have been clinically misdiagnosed as GET.

First described by Salama and Rosenthal³ in 2000, CCV remains a rarely reported entity, with approximately 33 reported cases in the worldwide literature.^2,4-7 The condition typically arises in adults with an equal predilection for males and females.² The true incidence of CCV is unknown and likely is underreported given its close similarities to GET, which often is diagnosed clinically. The unique histopathologic finding of superficial ectatic vascular spaces with eosinophilic hyalinized vessel walls in CCV is key to distinguishing these similar entities, and even this finding can be subtle and is easily overlooked. Inflammation is sparse to absent. Deposited material is positive on periodic acid-Schiff and cytokeratin IV staining (representing reduplicated basement membrane-type collagen) and is diastase resistant. Smooth muscle actin staining is diminished or absent. Ultrastructural examination reveals reduplicated, laminated basement membrane; Luse bodies (abnormally long, widely spaced collagen fibers); and a decrease in or loss of pericytes. Of note, Luse bodies are nonspecific and their absence does not exclude a diagnosis of CCV.¹

The etiology of CCV is unclear, and multiple pathogenetic mechanisms have been proposed. Ultimately, this entity is thought to arise from repeated endothelial cell damage, although the trigger for the endothelial cell injury is not completely understood. Diabetes mellitus sometimes is associated with microangiopathy and may be a confounding but not causative factor in some cases.¹ Some investigators believe CCV is caused by a genetic defect that alters collagen production in the small vessels of the skin.⁵ Others have hypothesized that it is a secondary manifestation of an underlying disease or is associated with a medication; however, no disease or drug has been convincingly implicated in CCV.⁸

Cutaneous collagenous vasculopathy is limited to the skin, with no known reports of systemic involvement in the literature.⁷ There are no recommended laboratory studies to aid in diagnosis.¹ It is critical to exclude hereditary hemorrhagic telangiectasia (HHT), as these patients can have life-threatening systemic involvement. Patients with CCV generally have no history of a bleeding diathesis, patients with HHT classically report recurrent epistaxis and gastrointestinal bleeding.⁷ A family history of HHT also is helpful for diagnosis, as the condition is autosomal dominant.¹ Neither HHT or telangiectasia macularis eruptiva perstans, which also can be included in the differential diagnosis, demonstrate vessel wall hyalinization. 

Treatment options for CCV are limited. Basso et al⁶ reported notable improvement in a patient with CCV treated with a combined 595-nm pulsed dye laser and 1064-nm Nd:YAG laser and optimized pulsed light. In one patient, treatment with a 585-nm pulsed dye laser produced a blanching response, suggesting that this may be a potential treatment option.⁷ Treatment with sclerotherapy has been ineffective.²

It is critical for both dermatologists and dermatopathologists to recognize and report this newly described entity, as the unique finding of vessel wall hyalinization in CCV may be indicative of a certain pathogenetic mechanism and effective treatment avenue that has yet to be established due to the relatively few number of reports that currently exist in the literature.

The Diagnosis: Cutaneous Collagenous Vasculopathy

Histopathologic examination revealed ectatic blood vessels lined with unremarkable endothelial cells and thickened, hyalinized vessel walls scattered within the papillary dermis (Figure 1). The epidermis was unremarkable. There was minimal associated inflammation and no extravasation of erythrocytes. The hyalinized material was weakly positive on periodic acid-Schiff staining (Figure 2) and negative on Congo red staining, which supported of a diagnosis of cutaneous collagenous vasculopathy (CCV).

The patient previously had been given a suspected diagnosis of generalized essential telangiectasia by an outside dermatologist several years prior to the current presentation, as CCV had yet to be recognized as its own entity and therefore few cases had been described in the literature. She had a known history of obesity, hypertension, hyperlipidemia, and type 2 diabetes mellitus, which are associated with the condition. Multiple specialists concluded that the disease was too extensive for laser treatment. A review of PubMed articles indexed for MEDLINE yielded no established treatment options.

Cutaneous collagenous vasculopathy is a rare acquired microangiopathy involving the small vessels of the skin. Its clinical presentation is indistinguishable from that of generalized essential telangiectasia (GET). Patients generally present with asymptomatic, widespread, blanching, symmetric telangiectasias that classically begin on the legs and steadily progress upward with classic sparing of the face (Figure 3). Whereas GET has been reported to involve the oral and conjunctival mucosa, mucosal involvement is not typically observed in CCV and is considered to be a distinguishing factor between the 2 conditions.^1,2 However, our patient reported oral symptoms, and oral erosions were seen on multiple physical examinations; therefore, ours is a rare case of mucosal involvement in conjunction with CCV. Given this finding, it is possible that more cases of CCV with mucosal involvement may exist but have been clinically misdiagnosed as GET.

First described by Salama and Rosenthal³ in 2000, CCV remains a rarely reported entity, with approximately 33 reported cases in the worldwide literature.^2,4-7 The condition typically arises in adults with an equal predilection for males and females.² The true incidence of CCV is unknown and likely is underreported given its close similarities to GET, which often is diagnosed clinically. The unique histopathologic finding of superficial ectatic vascular spaces with eosinophilic hyalinized vessel walls in CCV is key to distinguishing these similar entities, and even this finding can be subtle and is easily overlooked. Inflammation is sparse to absent. Deposited material is positive on periodic acid-Schiff and cytokeratin IV staining (representing reduplicated basement membrane-type collagen) and is diastase resistant. Smooth muscle actin staining is diminished or absent. Ultrastructural examination reveals reduplicated, laminated basement membrane; Luse bodies (abnormally long, widely spaced collagen fibers); and a decrease in or loss of pericytes. Of note, Luse bodies are nonspecific and their absence does not exclude a diagnosis of CCV.¹

The etiology of CCV is unclear, and multiple pathogenetic mechanisms have been proposed. Ultimately, this entity is thought to arise from repeated endothelial cell damage, although the trigger for the endothelial cell injury is not completely understood. Diabetes mellitus sometimes is associated with microangiopathy and may be a confounding but not causative factor in some cases.¹ Some investigators believe CCV is caused by a genetic defect that alters collagen production in the small vessels of the skin.⁵ Others have hypothesized that it is a secondary manifestation of an underlying disease or is associated with a medication; however, no disease or drug has been convincingly implicated in CCV.⁸

Cutaneous collagenous vasculopathy is limited to the skin, with no known reports of systemic involvement in the literature.⁷ There are no recommended laboratory studies to aid in diagnosis.¹ It is critical to exclude hereditary hemorrhagic telangiectasia (HHT), as these patients can have life-threatening systemic involvement. Patients with CCV generally have no history of a bleeding diathesis, patients with HHT classically report recurrent epistaxis and gastrointestinal bleeding.⁷ A family history of HHT also is helpful for diagnosis, as the condition is autosomal dominant.¹ Neither HHT or telangiectasia macularis eruptiva perstans, which also can be included in the differential diagnosis, demonstrate vessel wall hyalinization. 

Treatment options for CCV are limited. Basso et al⁶ reported notable improvement in a patient with CCV treated with a combined 595-nm pulsed dye laser and 1064-nm Nd:YAG laser and optimized pulsed light. In one patient, treatment with a 585-nm pulsed dye laser produced a blanching response, suggesting that this may be a potential treatment option.⁷ Treatment with sclerotherapy has been ineffective.²

It is critical for both dermatologists and dermatopathologists to recognize and report this newly described entity, as the unique finding of vessel wall hyalinization in CCV may be indicative of a certain pathogenetic mechanism and effective treatment avenue that has yet to be established due to the relatively few number of reports that currently exist in the literature.

The Diagnosis: Cutaneous Collagenous Vasculopathy

Histopathologic examination revealed ectatic blood vessels lined with unremarkable endothelial cells and thickened, hyalinized vessel walls scattered within the papillary dermis (Figure 1). The epidermis was unremarkable. There was minimal associated inflammation and no extravasation of erythrocytes. The hyalinized material was weakly positive on periodic acid-Schiff staining (Figure 2) and negative on Congo red staining, which supported of a diagnosis of cutaneous collagenous vasculopathy (CCV).

The patient previously had been given a suspected diagnosis of generalized essential telangiectasia by an outside dermatologist several years prior to the current presentation, as CCV had yet to be recognized as its own entity and therefore few cases had been described in the literature. She had a known history of obesity, hypertension, hyperlipidemia, and type 2 diabetes mellitus, which are associated with the condition. Multiple specialists concluded that the disease was too extensive for laser treatment. A review of PubMed articles indexed for MEDLINE yielded no established treatment options.

Cutaneous collagenous vasculopathy is a rare acquired microangiopathy involving the small vessels of the skin. Its clinical presentation is indistinguishable from that of generalized essential telangiectasia (GET). Patients generally present with asymptomatic, widespread, blanching, symmetric telangiectasias that classically begin on the legs and steadily progress upward with classic sparing of the face (Figure 3). Whereas GET has been reported to involve the oral and conjunctival mucosa, mucosal involvement is not typically observed in CCV and is considered to be a distinguishing factor between the 2 conditions.^1,2 However, our patient reported oral symptoms, and oral erosions were seen on multiple physical examinations; therefore, ours is a rare case of mucosal involvement in conjunction with CCV. Given this finding, it is possible that more cases of CCV with mucosal involvement may exist but have been clinically misdiagnosed as GET.

First described by Salama and Rosenthal³ in 2000, CCV remains a rarely reported entity, with approximately 33 reported cases in the worldwide literature.^2,4-7 The condition typically arises in adults with an equal predilection for males and females.² The true incidence of CCV is unknown and likely is underreported given its close similarities to GET, which often is diagnosed clinically. The unique histopathologic finding of superficial ectatic vascular spaces with eosinophilic hyalinized vessel walls in CCV is key to distinguishing these similar entities, and even this finding can be subtle and is easily overlooked. Inflammation is sparse to absent. Deposited material is positive on periodic acid-Schiff and cytokeratin IV staining (representing reduplicated basement membrane-type collagen) and is diastase resistant. Smooth muscle actin staining is diminished or absent. Ultrastructural examination reveals reduplicated, laminated basement membrane; Luse bodies (abnormally long, widely spaced collagen fibers); and a decrease in or loss of pericytes. Of note, Luse bodies are nonspecific and their absence does not exclude a diagnosis of CCV.¹

The etiology of CCV is unclear, and multiple pathogenetic mechanisms have been proposed. Ultimately, this entity is thought to arise from repeated endothelial cell damage, although the trigger for the endothelial cell injury is not completely understood. Diabetes mellitus sometimes is associated with microangiopathy and may be a confounding but not causative factor in some cases.¹ Some investigators believe CCV is caused by a genetic defect that alters collagen production in the small vessels of the skin.⁵ Others have hypothesized that it is a secondary manifestation of an underlying disease or is associated with a medication; however, no disease or drug has been convincingly implicated in CCV.⁸

Cutaneous collagenous vasculopathy is limited to the skin, with no known reports of systemic involvement in the literature.⁷ There are no recommended laboratory studies to aid in diagnosis.¹ It is critical to exclude hereditary hemorrhagic telangiectasia (HHT), as these patients can have life-threatening systemic involvement. Patients with CCV generally have no history of a bleeding diathesis, patients with HHT classically report recurrent epistaxis and gastrointestinal bleeding.⁷ A family history of HHT also is helpful for diagnosis, as the condition is autosomal dominant.¹ Neither HHT or telangiectasia macularis eruptiva perstans, which also can be included in the differential diagnosis, demonstrate vessel wall hyalinization. 

Treatment options for CCV are limited. Basso et al⁶ reported notable improvement in a patient with CCV treated with a combined 595-nm pulsed dye laser and 1064-nm Nd:YAG laser and optimized pulsed light. In one patient, treatment with a 585-nm pulsed dye laser produced a blanching response, suggesting that this may be a potential treatment option.⁷ Treatment with sclerotherapy has been ineffective.²

It is critical for both dermatologists and dermatopathologists to recognize and report this newly described entity, as the unique finding of vessel wall hyalinization in CCV may be indicative of a certain pathogenetic mechanism and effective treatment avenue that has yet to be established due to the relatively few number of reports that currently exist in the literature.