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The Diagnosis: Bullous Henoch-Schönlein Purpura

Laboratory tests in this patient showed no abnormalities for complete blood cell count, immunoglobulins, anti–double-stranded DNA, antinuclear antibody, p–antineutrophil cytoplasmic antibodies, lupus anticoagulant, Sjögren antibodies, liver enzymes, and erythrocyte sedimentation rate. Urinalysis was normal. Punch biopsies were obtained and a histologic examination showed an intense inflammatory infiltrate of neutrophils around blood vessels within the dermis (Figure). These blood vessels showed swollen endothelium and narrowing of the vessel lumina with leukocytoclasia. Direct immunofluorescence revealed granular IgA, C3, fibrin, and weak IgM deposits in blood vessels in the papillary dermis consistent with Henoch-Schönlein purpura (HSP).

Henoch-Schönlein purpura is the most common vasculitis in children.^1-6 However, its bullous variant is rare, with few pediatric cases reported. Bullous HSP affects arterioles through an IgA-mediated pathway.^1-6 It is believed that the bullae are formed secondary to neutrophilic release of matrix metalloproteinase 9 (MMP-9), which degrades extracellular collagen.² Additionally, bullous fluid from HSP has been noted to have markedly elevated levels of soluble CD23, a form of the CD23 B-cell surface receptor used in antibody feedback regulation and B-cell recruitment, which also has been found to be elevated in the fluid of bullous pemphigoid, suggesting a similar pathogenesis of exaggerated humoral immunity.³

The most common sign of HSP is palpable purpura; however, other cutaneous findings can be present including targetoid plaques, macules, papules, petechiae, and bullae that may become hemorrhagic, ulcerated, necrotic, or scarred.^1-6 Bullae appear in the most dependent parts of the body, such as the feet and lower legs. Hydrostatic pressure may play a role in the pathogenesis of this phenomenon.¹ When other classic signs of HSP are absent, the presence of bullae clouds the diagnosis and creates controversy regarding treatment, as there is a dearth of literature on proper therapy for severe cutaneous manifestations of HSP.⁶

Our patient was treated with morphine for pain management along with topical mupirocin and nonadherent dressings for wound care. She also received pulse intravenous methylprednisolone 2 mg/kg daily for 3 days and then was transitioned to oral prednisone 1 mg/kg daily, which was tapered over 3 weeks after discharge. This regimen resulted in resolution of symptoms with rapid regression of bullae and subsequent postinflammatory hyperpigmentation. Prior reports have noted that the presence of bullae does not alter the prognosis or predict probability of renal involvement of this self-limited disease, leading to controversy in determining if treatment offers more favorable outcomes.^1,3 One study suggested that steroids only improve symptoms, arthralgia, and abdominal pain, but they do not aid in the resolution of cutaneous lesions or prevent the progression of renal disease.³ Contrarily, others have suggested that the presence of bullae and renal disease is an indication to start treatment.⁶ This claim is based on the mechanistic finding that immunosuppression with corticosteroids decreases inflammation by inhibiting activator protein 1, a transcription factor for MMP-9, thereby reducing MMP-9 activity and the formation of bullae.⁴ Clinical anecdotes, including our own, that demonstrate dramatic improvement of hemorrhagic bullae with the administration of corticosteroids substantiate this mechanism. Through the inhibition of neutrophil interactions and IgA production, other anti-inflammatory and immunosuppressive medications such as colchicine, dapsone, and azathioprine also have been reported to aid in resolution of the cutaneous lesions.^1,5,6 Although there is a clear drawback to the lack of controlled trials and prospective studies regarding the treatment of bullous HSP, it is nearly impossible to expect such studies to be carried out given the rare and unpredictable nature of the disease. For now, claims derived from case series and case reports guide our understanding of treatment efficacy.

Acknowledgment—Quiz photograph courtesy of Steve Taylor, BS, Phoenix, Arizona.

The Diagnosis: Bullous Henoch-Schönlein Purpura

Laboratory tests in this patient showed no abnormalities for complete blood cell count, immunoglobulins, anti–double-stranded DNA, antinuclear antibody, p–antineutrophil cytoplasmic antibodies, lupus anticoagulant, Sjögren antibodies, liver enzymes, and erythrocyte sedimentation rate. Urinalysis was normal. Punch biopsies were obtained and a histologic examination showed an intense inflammatory infiltrate of neutrophils around blood vessels within the dermis (Figure). These blood vessels showed swollen endothelium and narrowing of the vessel lumina with leukocytoclasia. Direct immunofluorescence revealed granular IgA, C3, fibrin, and weak IgM deposits in blood vessels in the papillary dermis consistent with Henoch-Schönlein purpura (HSP).

Henoch-Schönlein purpura is the most common vasculitis in children.^1-6 However, its bullous variant is rare, with few pediatric cases reported. Bullous HSP affects arterioles through an IgA-mediated pathway.^1-6 It is believed that the bullae are formed secondary to neutrophilic release of matrix metalloproteinase 9 (MMP-9), which degrades extracellular collagen.² Additionally, bullous fluid from HSP has been noted to have markedly elevated levels of soluble CD23, a form of the CD23 B-cell surface receptor used in antibody feedback regulation and B-cell recruitment, which also has been found to be elevated in the fluid of bullous pemphigoid, suggesting a similar pathogenesis of exaggerated humoral immunity.³

The most common sign of HSP is palpable purpura; however, other cutaneous findings can be present including targetoid plaques, macules, papules, petechiae, and bullae that may become hemorrhagic, ulcerated, necrotic, or scarred.^1-6 Bullae appear in the most dependent parts of the body, such as the feet and lower legs. Hydrostatic pressure may play a role in the pathogenesis of this phenomenon.¹ When other classic signs of HSP are absent, the presence of bullae clouds the diagnosis and creates controversy regarding treatment, as there is a dearth of literature on proper therapy for severe cutaneous manifestations of HSP.⁶

Our patient was treated with morphine for pain management along with topical mupirocin and nonadherent dressings for wound care. She also received pulse intravenous methylprednisolone 2 mg/kg daily for 3 days and then was transitioned to oral prednisone 1 mg/kg daily, which was tapered over 3 weeks after discharge. This regimen resulted in resolution of symptoms with rapid regression of bullae and subsequent postinflammatory hyperpigmentation. Prior reports have noted that the presence of bullae does not alter the prognosis or predict probability of renal involvement of this self-limited disease, leading to controversy in determining if treatment offers more favorable outcomes.^1,3 One study suggested that steroids only improve symptoms, arthralgia, and abdominal pain, but they do not aid in the resolution of cutaneous lesions or prevent the progression of renal disease.³ Contrarily, others have suggested that the presence of bullae and renal disease is an indication to start treatment.⁶ This claim is based on the mechanistic finding that immunosuppression with corticosteroids decreases inflammation by inhibiting activator protein 1, a transcription factor for MMP-9, thereby reducing MMP-9 activity and the formation of bullae.⁴ Clinical anecdotes, including our own, that demonstrate dramatic improvement of hemorrhagic bullae with the administration of corticosteroids substantiate this mechanism. Through the inhibition of neutrophil interactions and IgA production, other anti-inflammatory and immunosuppressive medications such as colchicine, dapsone, and azathioprine also have been reported to aid in resolution of the cutaneous lesions.^1,5,6 Although there is a clear drawback to the lack of controlled trials and prospective studies regarding the treatment of bullous HSP, it is nearly impossible to expect such studies to be carried out given the rare and unpredictable nature of the disease. For now, claims derived from case series and case reports guide our understanding of treatment efficacy.

Acknowledgment—Quiz photograph courtesy of Steve Taylor, BS, Phoenix, Arizona.

The Diagnosis: Bullous Henoch-Schönlein Purpura

Laboratory tests in this patient showed no abnormalities for complete blood cell count, immunoglobulins, anti–double-stranded DNA, antinuclear antibody, p–antineutrophil cytoplasmic antibodies, lupus anticoagulant, Sjögren antibodies, liver enzymes, and erythrocyte sedimentation rate. Urinalysis was normal. Punch biopsies were obtained and a histologic examination showed an intense inflammatory infiltrate of neutrophils around blood vessels within the dermis (Figure). These blood vessels showed swollen endothelium and narrowing of the vessel lumina with leukocytoclasia. Direct immunofluorescence revealed granular IgA, C3, fibrin, and weak IgM deposits in blood vessels in the papillary dermis consistent with Henoch-Schönlein purpura (HSP).

Henoch-Schönlein purpura is the most common vasculitis in children.^1-6 However, its bullous variant is rare, with few pediatric cases reported. Bullous HSP affects arterioles through an IgA-mediated pathway.^1-6 It is believed that the bullae are formed secondary to neutrophilic release of matrix metalloproteinase 9 (MMP-9), which degrades extracellular collagen.² Additionally, bullous fluid from HSP has been noted to have markedly elevated levels of soluble CD23, a form of the CD23 B-cell surface receptor used in antibody feedback regulation and B-cell recruitment, which also has been found to be elevated in the fluid of bullous pemphigoid, suggesting a similar pathogenesis of exaggerated humoral immunity.³

The most common sign of HSP is palpable purpura; however, other cutaneous findings can be present including targetoid plaques, macules, papules, petechiae, and bullae that may become hemorrhagic, ulcerated, necrotic, or scarred.^1-6 Bullae appear in the most dependent parts of the body, such as the feet and lower legs. Hydrostatic pressure may play a role in the pathogenesis of this phenomenon.¹ When other classic signs of HSP are absent, the presence of bullae clouds the diagnosis and creates controversy regarding treatment, as there is a dearth of literature on proper therapy for severe cutaneous manifestations of HSP.⁶

Our patient was treated with morphine for pain management along with topical mupirocin and nonadherent dressings for wound care. She also received pulse intravenous methylprednisolone 2 mg/kg daily for 3 days and then was transitioned to oral prednisone 1 mg/kg daily, which was tapered over 3 weeks after discharge. This regimen resulted in resolution of symptoms with rapid regression of bullae and subsequent postinflammatory hyperpigmentation. Prior reports have noted that the presence of bullae does not alter the prognosis or predict probability of renal involvement of this self-limited disease, leading to controversy in determining if treatment offers more favorable outcomes.^1,3 One study suggested that steroids only improve symptoms, arthralgia, and abdominal pain, but they do not aid in the resolution of cutaneous lesions or prevent the progression of renal disease.³ Contrarily, others have suggested that the presence of bullae and renal disease is an indication to start treatment.⁶ This claim is based on the mechanistic finding that immunosuppression with corticosteroids decreases inflammation by inhibiting activator protein 1, a transcription factor for MMP-9, thereby reducing MMP-9 activity and the formation of bullae.⁴ Clinical anecdotes, including our own, that demonstrate dramatic improvement of hemorrhagic bullae with the administration of corticosteroids substantiate this mechanism. Through the inhibition of neutrophil interactions and IgA production, other anti-inflammatory and immunosuppressive medications such as colchicine, dapsone, and azathioprine also have been reported to aid in resolution of the cutaneous lesions.^1,5,6 Although there is a clear drawback to the lack of controlled trials and prospective studies regarding the treatment of bullous HSP, it is nearly impossible to expect such studies to be carried out given the rare and unpredictable nature of the disease. For now, claims derived from case series and case reports guide our understanding of treatment efficacy.

Acknowledgment—Quiz photograph courtesy of Steve Taylor, BS, Phoenix, Arizona.

The Diagnosis: Plexiform Neurofibroma as a Manifestation of Neurofibromatosis Type I

Physical examination revealed a large 10×8-cm subcutaneous nodule that was boggy and resembled a bag of worms on palpation. It was covered by slightly hyperpigmented skin. He also had numerous (>20) café au lait spots measuring 2 to 3 cm across the body and several others on the axillae. There were no gross eye findings. Otherwise the examination was unremarkable on the rest of the body. The patient’s paternal grandfather and aunt had similar macules and multiple nodules. The patient had mild to moderate learning difficulties. He was subsequently referred for genetic and ophthalmology evaluation.

Plexiform neurofibromas are usually benign nerve sheath tumors that are elongated and are multinodular, forming when the tumor involves either multiple trunks of a plexus or multiple fascicles of a large nerve such as the sciatic. Some plexiform neurofibromas resemble a bag of worms; others produce a massive ropy enlargement of the nerve.^1,2 Plexiform neurofibromas are associated with cases of neurofibromatosis type I (NFI) and are themselves one of the diagnostic criteria for NFI.¹

Plexiform neurofibromas are benign tumors that are the result of a genetic mutation in which loss of heterozygosity occurs, as is the case with the other predominant neoplasms of NFI, that results in unrestricted cell growth.^3,4 Some patients have a loss of heterozygosity of this tumor suppression gene with overgrowth of neurofibromatosis on a Blaschko segment. One study in mouse models showed that stromal mast cells were involved in promoting inflammation and increasing tumor growth by mediation of mitogenic signals involved in vascular ingrowth, collagen deposition, and cellular proliferation.⁵ Plexiform neurofibromas are a presenting feature in 30% of NFI cases within the first year of life. They are extensive nerve sheath tumors with an unpredictable growth pattern that can involve multiple fascicles (ie, large nerves and their branches). Five percent become malignant and the transformation is often heralded by rapid growth and pain.⁶ If malignant transformation is suspected, biopsy is diagnostic. Magnetic resonance imaging with and without contrast can categorize them into 3 growth categories: superficial, displacing, and invasive.⁷ Because plexiform neurofibromas are rare tumors, it previously was common practice to delay surgical intervention until disfigurement or disability arose. Complete surgical resection at more advanced stages is nearly impossible given the networklike growth pattern that commonly encapsulates vital structures.^8,9 Therefore, surgery has been used in the past for debulking the large growths that eventually will recur. A study of 9 small superficial plexiform neurofibromas in children aged 3 to 15 years documented treatment with early surgical resection, which showed complete resection and no relapse at 4 years. This study showed a promising strategy to prevent future extension of these fast-growing tumors into vital structures.⁸ There also are current clinical trials investigating sirolimus and peginterferon alfa-2b in patients with more invasive plexiform neurofibromas that are unable to undergo surgical resection due to encapsulation or proximity to essential anatomical structures (registered at www.clinicaltrials.gov with the identifiers NCT00652990 and NCT00678951, respectively).

Pain, development of a neurologic deficit, or enlargement of a preexisting plexiform neurofibroma may signal a malignant peripheral nerve sheath tumor (MPNST) and require immediate evaluation.¹⁰ Examination by magnetic resonance imaging and positron emission tomography is useful in distinguishing benign and MPNSTs,^8,11,12 but definitive differentiation can only be made by histologic examination of the tumor. Complete surgical excision, when possible, is the only treatment that offers the possibility of cure of MPNSTs. Adjuvant chemotherapy or radiotherapy also is sometimes used, though benefit has not been clearly established.^8,9,13,14

Death certificate and population-based studies have shown that approximately 10% of patients with NFI have a reduced life expectancy due to MPNSTs; indeed, these tumors arising from plexiform neurofibromas are the main cause of death in adults with NFI. In 2003, Mautner et al⁷ studied 50 individuals with NFI. The objective was to establish magnetic resonance imaging criteria for MPNST and to test their usefulness in detecting early malignant change in plexiform neurofibromas. This study found that MPNST in patients with NFI frequently showed inhomogeneous contrast enhancement. This inhomogeneity was due to necrosis and hemorrhage, as shown by macroscopic and histologic analysis of amputated limbs in 2 patients within the study. The investigators found it to be possible to detect malignant transformation at an early stage in patients with no overt clinical signs of progression.⁷ Careful follow-up will determine how frequently early malignancy can be detected and if it is worthwhile carrying out magnetic resonance imaging at defined intervals.^2,7,10,15,16

The Diagnosis: Plexiform Neurofibroma as a Manifestation of Neurofibromatosis Type I

Physical examination revealed a large 10×8-cm subcutaneous nodule that was boggy and resembled a bag of worms on palpation. It was covered by slightly hyperpigmented skin. He also had numerous (>20) café au lait spots measuring 2 to 3 cm across the body and several others on the axillae. There were no gross eye findings. Otherwise the examination was unremarkable on the rest of the body. The patient’s paternal grandfather and aunt had similar macules and multiple nodules. The patient had mild to moderate learning difficulties. He was subsequently referred for genetic and ophthalmology evaluation.

Plexiform neurofibromas are usually benign nerve sheath tumors that are elongated and are multinodular, forming when the tumor involves either multiple trunks of a plexus or multiple fascicles of a large nerve such as the sciatic. Some plexiform neurofibromas resemble a bag of worms; others produce a massive ropy enlargement of the nerve.^1,2 Plexiform neurofibromas are associated with cases of neurofibromatosis type I (NFI) and are themselves one of the diagnostic criteria for NFI.¹

Plexiform neurofibromas are benign tumors that are the result of a genetic mutation in which loss of heterozygosity occurs, as is the case with the other predominant neoplasms of NFI, that results in unrestricted cell growth.^3,4 Some patients have a loss of heterozygosity of this tumor suppression gene with overgrowth of neurofibromatosis on a Blaschko segment. One study in mouse models showed that stromal mast cells were involved in promoting inflammation and increasing tumor growth by mediation of mitogenic signals involved in vascular ingrowth, collagen deposition, and cellular proliferation.⁵ Plexiform neurofibromas are a presenting feature in 30% of NFI cases within the first year of life. They are extensive nerve sheath tumors with an unpredictable growth pattern that can involve multiple fascicles (ie, large nerves and their branches). Five percent become malignant and the transformation is often heralded by rapid growth and pain.⁶ If malignant transformation is suspected, biopsy is diagnostic. Magnetic resonance imaging with and without contrast can categorize them into 3 growth categories: superficial, displacing, and invasive.⁷ Because plexiform neurofibromas are rare tumors, it previously was common practice to delay surgical intervention until disfigurement or disability arose. Complete surgical resection at more advanced stages is nearly impossible given the networklike growth pattern that commonly encapsulates vital structures.^8,9 Therefore, surgery has been used in the past for debulking the large growths that eventually will recur. A study of 9 small superficial plexiform neurofibromas in children aged 3 to 15 years documented treatment with early surgical resection, which showed complete resection and no relapse at 4 years. This study showed a promising strategy to prevent future extension of these fast-growing tumors into vital structures.⁸ There also are current clinical trials investigating sirolimus and peginterferon alfa-2b in patients with more invasive plexiform neurofibromas that are unable to undergo surgical resection due to encapsulation or proximity to essential anatomical structures (registered at www.clinicaltrials.gov with the identifiers NCT00652990 and NCT00678951, respectively).

Pain, development of a neurologic deficit, or enlargement of a preexisting plexiform neurofibroma may signal a malignant peripheral nerve sheath tumor (MPNST) and require immediate evaluation.¹⁰ Examination by magnetic resonance imaging and positron emission tomography is useful in distinguishing benign and MPNSTs,^8,11,12 but definitive differentiation can only be made by histologic examination of the tumor. Complete surgical excision, when possible, is the only treatment that offers the possibility of cure of MPNSTs. Adjuvant chemotherapy or radiotherapy also is sometimes used, though benefit has not been clearly established.^8,9,13,14

Death certificate and population-based studies have shown that approximately 10% of patients with NFI have a reduced life expectancy due to MPNSTs; indeed, these tumors arising from plexiform neurofibromas are the main cause of death in adults with NFI. In 2003, Mautner et al⁷ studied 50 individuals with NFI. The objective was to establish magnetic resonance imaging criteria for MPNST and to test their usefulness in detecting early malignant change in plexiform neurofibromas. This study found that MPNST in patients with NFI frequently showed inhomogeneous contrast enhancement. This inhomogeneity was due to necrosis and hemorrhage, as shown by macroscopic and histologic analysis of amputated limbs in 2 patients within the study. The investigators found it to be possible to detect malignant transformation at an early stage in patients with no overt clinical signs of progression.⁷ Careful follow-up will determine how frequently early malignancy can be detected and if it is worthwhile carrying out magnetic resonance imaging at defined intervals.^2,7,10,15,16

The Diagnosis: Plexiform Neurofibroma as a Manifestation of Neurofibromatosis Type I

Physical examination revealed a large 10×8-cm subcutaneous nodule that was boggy and resembled a bag of worms on palpation. It was covered by slightly hyperpigmented skin. He also had numerous (>20) café au lait spots measuring 2 to 3 cm across the body and several others on the axillae. There were no gross eye findings. Otherwise the examination was unremarkable on the rest of the body. The patient’s paternal grandfather and aunt had similar macules and multiple nodules. The patient had mild to moderate learning difficulties. He was subsequently referred for genetic and ophthalmology evaluation.

Plexiform neurofibromas are usually benign nerve sheath tumors that are elongated and are multinodular, forming when the tumor involves either multiple trunks of a plexus or multiple fascicles of a large nerve such as the sciatic. Some plexiform neurofibromas resemble a bag of worms; others produce a massive ropy enlargement of the nerve.^1,2 Plexiform neurofibromas are associated with cases of neurofibromatosis type I (NFI) and are themselves one of the diagnostic criteria for NFI.¹

Plexiform neurofibromas are benign tumors that are the result of a genetic mutation in which loss of heterozygosity occurs, as is the case with the other predominant neoplasms of NFI, that results in unrestricted cell growth.^3,4 Some patients have a loss of heterozygosity of this tumor suppression gene with overgrowth of neurofibromatosis on a Blaschko segment. One study in mouse models showed that stromal mast cells were involved in promoting inflammation and increasing tumor growth by mediation of mitogenic signals involved in vascular ingrowth, collagen deposition, and cellular proliferation.⁵ Plexiform neurofibromas are a presenting feature in 30% of NFI cases within the first year of life. They are extensive nerve sheath tumors with an unpredictable growth pattern that can involve multiple fascicles (ie, large nerves and their branches). Five percent become malignant and the transformation is often heralded by rapid growth and pain.⁶ If malignant transformation is suspected, biopsy is diagnostic. Magnetic resonance imaging with and without contrast can categorize them into 3 growth categories: superficial, displacing, and invasive.⁷ Because plexiform neurofibromas are rare tumors, it previously was common practice to delay surgical intervention until disfigurement or disability arose. Complete surgical resection at more advanced stages is nearly impossible given the networklike growth pattern that commonly encapsulates vital structures.^8,9 Therefore, surgery has been used in the past for debulking the large growths that eventually will recur. A study of 9 small superficial plexiform neurofibromas in children aged 3 to 15 years documented treatment with early surgical resection, which showed complete resection and no relapse at 4 years. This study showed a promising strategy to prevent future extension of these fast-growing tumors into vital structures.⁸ There also are current clinical trials investigating sirolimus and peginterferon alfa-2b in patients with more invasive plexiform neurofibromas that are unable to undergo surgical resection due to encapsulation or proximity to essential anatomical structures (registered at www.clinicaltrials.gov with the identifiers NCT00652990 and NCT00678951, respectively).

Pain, development of a neurologic deficit, or enlargement of a preexisting plexiform neurofibroma may signal a malignant peripheral nerve sheath tumor (MPNST) and require immediate evaluation.¹⁰ Examination by magnetic resonance imaging and positron emission tomography is useful in distinguishing benign and MPNSTs,^8,11,12 but definitive differentiation can only be made by histologic examination of the tumor. Complete surgical excision, when possible, is the only treatment that offers the possibility of cure of MPNSTs. Adjuvant chemotherapy or radiotherapy also is sometimes used, though benefit has not been clearly established.^8,9,13,14

Death certificate and population-based studies have shown that approximately 10% of patients with NFI have a reduced life expectancy due to MPNSTs; indeed, these tumors arising from plexiform neurofibromas are the main cause of death in adults with NFI. In 2003, Mautner et al⁷ studied 50 individuals with NFI. The objective was to establish magnetic resonance imaging criteria for MPNST and to test their usefulness in detecting early malignant change in plexiform neurofibromas. This study found that MPNST in patients with NFI frequently showed inhomogeneous contrast enhancement. This inhomogeneity was due to necrosis and hemorrhage, as shown by macroscopic and histologic analysis of amputated limbs in 2 patients within the study. The investigators found it to be possible to detect malignant transformation at an early stage in patients with no overt clinical signs of progression.⁷ Careful follow-up will determine how frequently early malignancy can be detected and if it is worthwhile carrying out magnetic resonance imaging at defined intervals.^2,7,10,15,16

The Diagnosis: Mycosis Fungoides

Physical examination revealed erythematous polycyclic and arcuate plaques with fine overlying scale on the right arm and shoulder (Figure 1). Mild wrinkling and telangiectasias were noted on the skin surrounding the lesions. Laboratory tests showed normal values for antinuclear antibodies, anti–Sjögren syndrome–related antigen A, and anti–Sjögren syndrome–related antigen B.

A skin biopsy of a plaque on the right upper arm showed enlarged pleomorphic lymphocytes arranged along the basal layer and in focal collections within the epidermis (Figure 2). Within the dermis were wiry bundles of collagen, a sparse superficial and patchy infiltrate of lymphocytes, and scattered large mononuclear cells (Figure 3). Immunoperoxidase staining revealed large intraepidermal lymphocytes positive for CD4 (Figure 4A) and CD5. Notably, these lymphocytes also stained positive for CD30 (Figure 4B). Staining for CD8, CD1a, CD56, and anaplastic lymphoma kinase was negative, with aberrant loss of CD3. The morphology and pattern of immunoreactivity supported the diagnosis of mycosis fungoides (MF).

Mycosis fungoides is the most common form of cutaneous T-cell lymphoma.¹ Its progression is classified in 3 stages: (1) early (patch) stage, (2) plaque stage, and (3) tumor stage. Conclusive diagnosis of early stage MF often is difficult due to its clinical features that are similar to more common benign dermatoses (eg, atopic dermatitis, psoriasis, lichen planus), leading to shortcomings in determining prognosis and selecting an appropriate treatment regimen. With this diagnositic difficulty in mind, guidelines have been created to aid in the diagnosis of early stage MF.²

Clinical features consistent with early stage MF include multiple erythematous, well-demarcated lesions with varying shapes that typically are greater than 5 cm in diameter.² Lesions usually are flat or thinly elevated and may exhibit slight scaling. As was noted in our patient, poikiloderma of the surrounding skin is fairly specific for early stage MF, as it is not a feature associated with common clinical mimics of MF (eg, atopic dermatitis, psoriasis, lichen planus). The distribution of skin lesions in non–sun-exposed areas is common. The eruption is persistent, though it may wax and wane in severity.²
 

Histopathologic examination is necessary to confirm a diagnosis of MF. Typically, early stage MF is marked by enlarged T lymphocytes within the epidermis as well as the papillary and superficial reticular dermis. Cerebriform nuclei are a key finding in the diagnosis of MF. Lymphocytes frequently are arranged linearly along the basal layer of the epidermis. Within the epidermis, clusters of atypical lymphocytes (Pautrier microabscesses) without spongiosis are uncommon but are a characteristic finding of MF if present.¹ Papillary dermal fibrosis also may be evident.²
 

Figure 4. Large intraepidermal lymphocytes were highlighted on CD4 (A) and CD30 immunostaining (B)(original magnification ×200 and ×200).

Immunostaining typically reveals positivity for CD3 and CD4, as well as for lymphocyte antigens CD2 and CD5.¹ CD30 positivity in early stage MF rarely has been reported in the literature.^3,4 Such cases appear histologically similarly to CD30‒negative cases in other respects. One study showed that the presence of CD30-positive lymphocytes does not alter the clinical course of MF.³ Another study found that, while epidermal CD30-postive lymphocytes had no prognostic relevance, an increased percentage of dermal CD30-positive cells was linked to a higher stage at diagnosis and worse overall prognosis.⁵ Pathogenesis underlying CD30 positivity in early MF is unknown. It is important to note that CD30-positive cells commonly are seen in lymphomatoid papulosis and anaplastic large cell lymphoma, as well as a variety of nonneoplastic conditions.^3,6,7

The Diagnosis: Mycosis Fungoides

Physical examination revealed erythematous polycyclic and arcuate plaques with fine overlying scale on the right arm and shoulder (Figure 1). Mild wrinkling and telangiectasias were noted on the skin surrounding the lesions. Laboratory tests showed normal values for antinuclear antibodies, anti–Sjögren syndrome–related antigen A, and anti–Sjögren syndrome–related antigen B.

A skin biopsy of a plaque on the right upper arm showed enlarged pleomorphic lymphocytes arranged along the basal layer and in focal collections within the epidermis (Figure 2). Within the dermis were wiry bundles of collagen, a sparse superficial and patchy infiltrate of lymphocytes, and scattered large mononuclear cells (Figure 3). Immunoperoxidase staining revealed large intraepidermal lymphocytes positive for CD4 (Figure 4A) and CD5. Notably, these lymphocytes also stained positive for CD30 (Figure 4B). Staining for CD8, CD1a, CD56, and anaplastic lymphoma kinase was negative, with aberrant loss of CD3. The morphology and pattern of immunoreactivity supported the diagnosis of mycosis fungoides (MF).

Mycosis fungoides is the most common form of cutaneous T-cell lymphoma.¹ Its progression is classified in 3 stages: (1) early (patch) stage, (2) plaque stage, and (3) tumor stage. Conclusive diagnosis of early stage MF often is difficult due to its clinical features that are similar to more common benign dermatoses (eg, atopic dermatitis, psoriasis, lichen planus), leading to shortcomings in determining prognosis and selecting an appropriate treatment regimen. With this diagnositic difficulty in mind, guidelines have been created to aid in the diagnosis of early stage MF.²

Clinical features consistent with early stage MF include multiple erythematous, well-demarcated lesions with varying shapes that typically are greater than 5 cm in diameter.² Lesions usually are flat or thinly elevated and may exhibit slight scaling. As was noted in our patient, poikiloderma of the surrounding skin is fairly specific for early stage MF, as it is not a feature associated with common clinical mimics of MF (eg, atopic dermatitis, psoriasis, lichen planus). The distribution of skin lesions in non–sun-exposed areas is common. The eruption is persistent, though it may wax and wane in severity.²
 

Histopathologic examination is necessary to confirm a diagnosis of MF. Typically, early stage MF is marked by enlarged T lymphocytes within the epidermis as well as the papillary and superficial reticular dermis. Cerebriform nuclei are a key finding in the diagnosis of MF. Lymphocytes frequently are arranged linearly along the basal layer of the epidermis. Within the epidermis, clusters of atypical lymphocytes (Pautrier microabscesses) without spongiosis are uncommon but are a characteristic finding of MF if present.¹ Papillary dermal fibrosis also may be evident.²
 

Figure 4. Large intraepidermal lymphocytes were highlighted on CD4 (A) and CD30 immunostaining (B)(original magnification ×200 and ×200).

Immunostaining typically reveals positivity for CD3 and CD4, as well as for lymphocyte antigens CD2 and CD5.¹ CD30 positivity in early stage MF rarely has been reported in the literature.^3,4 Such cases appear histologically similarly to CD30‒negative cases in other respects. One study showed that the presence of CD30-positive lymphocytes does not alter the clinical course of MF.³ Another study found that, while epidermal CD30-postive lymphocytes had no prognostic relevance, an increased percentage of dermal CD30-positive cells was linked to a higher stage at diagnosis and worse overall prognosis.⁵ Pathogenesis underlying CD30 positivity in early MF is unknown. It is important to note that CD30-positive cells commonly are seen in lymphomatoid papulosis and anaplastic large cell lymphoma, as well as a variety of nonneoplastic conditions.^3,6,7

The Diagnosis: Mycosis Fungoides

Physical examination revealed erythematous polycyclic and arcuate plaques with fine overlying scale on the right arm and shoulder (Figure 1). Mild wrinkling and telangiectasias were noted on the skin surrounding the lesions. Laboratory tests showed normal values for antinuclear antibodies, anti–Sjögren syndrome–related antigen A, and anti–Sjögren syndrome–related antigen B.

A skin biopsy of a plaque on the right upper arm showed enlarged pleomorphic lymphocytes arranged along the basal layer and in focal collections within the epidermis (Figure 2). Within the dermis were wiry bundles of collagen, a sparse superficial and patchy infiltrate of lymphocytes, and scattered large mononuclear cells (Figure 3). Immunoperoxidase staining revealed large intraepidermal lymphocytes positive for CD4 (Figure 4A) and CD5. Notably, these lymphocytes also stained positive for CD30 (Figure 4B). Staining for CD8, CD1a, CD56, and anaplastic lymphoma kinase was negative, with aberrant loss of CD3. The morphology and pattern of immunoreactivity supported the diagnosis of mycosis fungoides (MF).

Mycosis fungoides is the most common form of cutaneous T-cell lymphoma.¹ Its progression is classified in 3 stages: (1) early (patch) stage, (2) plaque stage, and (3) tumor stage. Conclusive diagnosis of early stage MF often is difficult due to its clinical features that are similar to more common benign dermatoses (eg, atopic dermatitis, psoriasis, lichen planus), leading to shortcomings in determining prognosis and selecting an appropriate treatment regimen. With this diagnositic difficulty in mind, guidelines have been created to aid in the diagnosis of early stage MF.²

Clinical features consistent with early stage MF include multiple erythematous, well-demarcated lesions with varying shapes that typically are greater than 5 cm in diameter.² Lesions usually are flat or thinly elevated and may exhibit slight scaling. As was noted in our patient, poikiloderma of the surrounding skin is fairly specific for early stage MF, as it is not a feature associated with common clinical mimics of MF (eg, atopic dermatitis, psoriasis, lichen planus). The distribution of skin lesions in non–sun-exposed areas is common. The eruption is persistent, though it may wax and wane in severity.²
 

Histopathologic examination is necessary to confirm a diagnosis of MF. Typically, early stage MF is marked by enlarged T lymphocytes within the epidermis as well as the papillary and superficial reticular dermis. Cerebriform nuclei are a key finding in the diagnosis of MF. Lymphocytes frequently are arranged linearly along the basal layer of the epidermis. Within the epidermis, clusters of atypical lymphocytes (Pautrier microabscesses) without spongiosis are uncommon but are a characteristic finding of MF if present.¹ Papillary dermal fibrosis also may be evident.²
 

Figure 4. Large intraepidermal lymphocytes were highlighted on CD4 (A) and CD30 immunostaining (B)(original magnification ×200 and ×200).

Immunostaining typically reveals positivity for CD3 and CD4, as well as for lymphocyte antigens CD2 and CD5.¹ CD30 positivity in early stage MF rarely has been reported in the literature.^3,4 Such cases appear histologically similarly to CD30‒negative cases in other respects. One study showed that the presence of CD30-positive lymphocytes does not alter the clinical course of MF.³ Another study found that, while epidermal CD30-postive lymphocytes had no prognostic relevance, an increased percentage of dermal CD30-positive cells was linked to a higher stage at diagnosis and worse overall prognosis.⁵ Pathogenesis underlying CD30 positivity in early MF is unknown. It is important to note that CD30-positive cells commonly are seen in lymphomatoid papulosis and anaplastic large cell lymphoma, as well as a variety of nonneoplastic conditions.^3,6,7

The Diagnosis: Neutrophilic Dermatosis of the Dorsal Hands

Neutrophilic dermatosis of the dorsal hands (NDDH) is considered to be an uncommon localized variant of Sweet syndrome (SS). The term pustular vasculitis originally was used to describe this condition by Strutton et al¹ in 1995 due to the presence of leukocytoclastic vasculitis on histology. In 2000, Galaria et al² suggested this eruption was a localized variant of SS based on clinical presentations that demonstrated associated fever and lack of necrotizing vasculitis and proposed the term neutrophilic dermatosis of the dorsal hands to describe the condition. Cases of similar cutaneous eruptions on the hands associated with fever, leukocytosis, elevated erythrocyte sedimentation rate, and leukocytoclasis have since been reported.^3-5 Some authors have concluded that these eruptions, previously termed atypical pyoderma gangrenosum and pustular vasculitis of the hands, represent a single disease entity and should be designated as NDDH.^3,4

Neutrophilic dermatosis of the dorsal hands characteristically presents with hemorrhagic pustular ulcerations limited to or predominantly located on the dorsal hands, as seen in our patient. Histopathologically, NDDH demonstrates a neutrophil-predominant infiltrate of the upper dermis and marked papillary dermal edema; a punch biopsy specimen from our patient was consistent with these features (Figure). Two punch biopsies were performed and were negative for fungus and acid-fast bacteria and positive for methicillin-sensitive Staphylococcus aureus. Vasculitis, if present, is more commonly seen in eruptions of longer duration (ie, months to years) and is thought to be secondary to the dense neutrophilic infiltrate and not a primary vasculitis.^3,6,7 Similar to classic SS, NDDH is inherently responsive to corticosteroid therapy. Successful treatment also has been reported with dapsone, colchicine, sulfapyridine, potassium iodide, intralesional and topical corticosteroids, and topical tacrolimus.^2-8 Oral minocycline has shown variable results.^3,4

Numerous case series have demonstrated that a majority of cases of NDDH are associated with hematologic or solid organ malignancies, myelodysplastic syndrome (MDS), inflammatory bowel disease, or other underlying systemic diseases.^3,5,9 It is important for dermatologists to recognize NDDH, distinguish it from localized infection, and perform the appropriate workup (eg, basic laboratory tests [complete blood count, complete metabolic panel], age-appropriate malignancy screening, colonoscopy, bone marrow biopsy) to exclude associated systemic diseases.

Our patient demonstrated characteristic clinical and histopathologic findings of NDDH in association with early MDS and possible common bile duct (CBD) malignancy. The lesions showed a rapid response to topical corticosteroid therapy. The initial differential diagnoses included NDDH or other neutrophilic dermatosis, phototoxic drug eruption, and atypical mycobacterial or fungal infection (cultures were negative in our patient). Physical examination and histopathologic findings along with the patient’s clinical course and rapid response to topical corticosteroid therapy supported the diagnosis of NDDH. Our patient’s multiple comorbidities, including macrocytic anemia, MDS, and potential CBD malignancy, presented a therapeutic challenge. Oral dapsone, an ideal steroid-sparing agent for neutrophilic dermatoses including NDDH, was avoided given its associated hematologic side effects including hemolysis, methemoglobinemia, and possible agranulocytosis. To date, the patient has not received any further treatment for MDS or the CBD mass and continues regular follow-up with hematology, gastroenterology, and dermatology.

This case highlights the importance of including NDDH in the differential diagnosis of papules and plaques on the hands, especially in patients with known malignancies, and emphasizes the association of neutrophilic dermatoses with malignancy and systemic disease. 

The Diagnosis: Neutrophilic Dermatosis of the Dorsal Hands

Neutrophilic dermatosis of the dorsal hands (NDDH) is considered to be an uncommon localized variant of Sweet syndrome (SS). The term pustular vasculitis originally was used to describe this condition by Strutton et al¹ in 1995 due to the presence of leukocytoclastic vasculitis on histology. In 2000, Galaria et al² suggested this eruption was a localized variant of SS based on clinical presentations that demonstrated associated fever and lack of necrotizing vasculitis and proposed the term neutrophilic dermatosis of the dorsal hands to describe the condition. Cases of similar cutaneous eruptions on the hands associated with fever, leukocytosis, elevated erythrocyte sedimentation rate, and leukocytoclasis have since been reported.^3-5 Some authors have concluded that these eruptions, previously termed atypical pyoderma gangrenosum and pustular vasculitis of the hands, represent a single disease entity and should be designated as NDDH.^3,4

Neutrophilic dermatosis of the dorsal hands characteristically presents with hemorrhagic pustular ulcerations limited to or predominantly located on the dorsal hands, as seen in our patient. Histopathologically, NDDH demonstrates a neutrophil-predominant infiltrate of the upper dermis and marked papillary dermal edema; a punch biopsy specimen from our patient was consistent with these features (Figure). Two punch biopsies were performed and were negative for fungus and acid-fast bacteria and positive for methicillin-sensitive Staphylococcus aureus. Vasculitis, if present, is more commonly seen in eruptions of longer duration (ie, months to years) and is thought to be secondary to the dense neutrophilic infiltrate and not a primary vasculitis.^3,6,7 Similar to classic SS, NDDH is inherently responsive to corticosteroid therapy. Successful treatment also has been reported with dapsone, colchicine, sulfapyridine, potassium iodide, intralesional and topical corticosteroids, and topical tacrolimus.^2-8 Oral minocycline has shown variable results.^3,4

Numerous case series have demonstrated that a majority of cases of NDDH are associated with hematologic or solid organ malignancies, myelodysplastic syndrome (MDS), inflammatory bowel disease, or other underlying systemic diseases.^3,5,9 It is important for dermatologists to recognize NDDH, distinguish it from localized infection, and perform the appropriate workup (eg, basic laboratory tests [complete blood count, complete metabolic panel], age-appropriate malignancy screening, colonoscopy, bone marrow biopsy) to exclude associated systemic diseases.

Our patient demonstrated characteristic clinical and histopathologic findings of NDDH in association with early MDS and possible common bile duct (CBD) malignancy. The lesions showed a rapid response to topical corticosteroid therapy. The initial differential diagnoses included NDDH or other neutrophilic dermatosis, phototoxic drug eruption, and atypical mycobacterial or fungal infection (cultures were negative in our patient). Physical examination and histopathologic findings along with the patient’s clinical course and rapid response to topical corticosteroid therapy supported the diagnosis of NDDH. Our patient’s multiple comorbidities, including macrocytic anemia, MDS, and potential CBD malignancy, presented a therapeutic challenge. Oral dapsone, an ideal steroid-sparing agent for neutrophilic dermatoses including NDDH, was avoided given its associated hematologic side effects including hemolysis, methemoglobinemia, and possible agranulocytosis. To date, the patient has not received any further treatment for MDS or the CBD mass and continues regular follow-up with hematology, gastroenterology, and dermatology.

This case highlights the importance of including NDDH in the differential diagnosis of papules and plaques on the hands, especially in patients with known malignancies, and emphasizes the association of neutrophilic dermatoses with malignancy and systemic disease. 

The Diagnosis: Neutrophilic Dermatosis of the Dorsal Hands

Neutrophilic dermatosis of the dorsal hands (NDDH) is considered to be an uncommon localized variant of Sweet syndrome (SS). The term pustular vasculitis originally was used to describe this condition by Strutton et al¹ in 1995 due to the presence of leukocytoclastic vasculitis on histology. In 2000, Galaria et al² suggested this eruption was a localized variant of SS based on clinical presentations that demonstrated associated fever and lack of necrotizing vasculitis and proposed the term neutrophilic dermatosis of the dorsal hands to describe the condition. Cases of similar cutaneous eruptions on the hands associated with fever, leukocytosis, elevated erythrocyte sedimentation rate, and leukocytoclasis have since been reported.^3-5 Some authors have concluded that these eruptions, previously termed atypical pyoderma gangrenosum and pustular vasculitis of the hands, represent a single disease entity and should be designated as NDDH.^3,4

Neutrophilic dermatosis of the dorsal hands characteristically presents with hemorrhagic pustular ulcerations limited to or predominantly located on the dorsal hands, as seen in our patient. Histopathologically, NDDH demonstrates a neutrophil-predominant infiltrate of the upper dermis and marked papillary dermal edema; a punch biopsy specimen from our patient was consistent with these features (Figure). Two punch biopsies were performed and were negative for fungus and acid-fast bacteria and positive for methicillin-sensitive Staphylococcus aureus. Vasculitis, if present, is more commonly seen in eruptions of longer duration (ie, months to years) and is thought to be secondary to the dense neutrophilic infiltrate and not a primary vasculitis.^3,6,7 Similar to classic SS, NDDH is inherently responsive to corticosteroid therapy. Successful treatment also has been reported with dapsone, colchicine, sulfapyridine, potassium iodide, intralesional and topical corticosteroids, and topical tacrolimus.^2-8 Oral minocycline has shown variable results.^3,4

Numerous case series have demonstrated that a majority of cases of NDDH are associated with hematologic or solid organ malignancies, myelodysplastic syndrome (MDS), inflammatory bowel disease, or other underlying systemic diseases.^3,5,9 It is important for dermatologists to recognize NDDH, distinguish it from localized infection, and perform the appropriate workup (eg, basic laboratory tests [complete blood count, complete metabolic panel], age-appropriate malignancy screening, colonoscopy, bone marrow biopsy) to exclude associated systemic diseases.

Our patient demonstrated characteristic clinical and histopathologic findings of NDDH in association with early MDS and possible common bile duct (CBD) malignancy. The lesions showed a rapid response to topical corticosteroid therapy. The initial differential diagnoses included NDDH or other neutrophilic dermatosis, phototoxic drug eruption, and atypical mycobacterial or fungal infection (cultures were negative in our patient). Physical examination and histopathologic findings along with the patient’s clinical course and rapid response to topical corticosteroid therapy supported the diagnosis of NDDH. Our patient’s multiple comorbidities, including macrocytic anemia, MDS, and potential CBD malignancy, presented a therapeutic challenge. Oral dapsone, an ideal steroid-sparing agent for neutrophilic dermatoses including NDDH, was avoided given its associated hematologic side effects including hemolysis, methemoglobinemia, and possible agranulocytosis. To date, the patient has not received any further treatment for MDS or the CBD mass and continues regular follow-up with hematology, gastroenterology, and dermatology.

This case highlights the importance of including NDDH in the differential diagnosis of papules and plaques on the hands, especially in patients with known malignancies, and emphasizes the association of neutrophilic dermatoses with malignancy and systemic disease. 

The Diagnosis: Hyperkeratosis Lenticularis Perstans

A shave biopsy of a lesion on the right leg was performed. Histopathology revealed a discrete papule with overlying compact hyperkeratosis. There was parakeratosis with an absent granular layer and a lichenoid lymphocytic infiltrate within the papillary dermis (Figure). Given the clinical context, these changes were consistent with a diagnosis of hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease.

The patient was started on tretinoin cream 0.1% nightly for 3 months and triamcinolone ointment 0.1% as needed for pruritus but showed no clinical response. Given the benign nature of the condition and because the lesions were asymptomatic, additional treatment options were not pursued.

Originally described by Flegel¹ in 1958, HLP is a rare skin disorder commonly seen in white individuals with onset in the fourth or fifth decades of life.^1,2 While most cases are sporadic,^3-6 HLP also has been associated with autosomal dominant inheritance.^7-10

Patients with HLP typically present with multiple 1- to 5-mm reddish-brown, hyperkeratotic, scaly papules that reveal a moist, erythematous base with pinpoint bleeding upon removal of the scale. Lesions usually are distributed symmetrically and most commonly present on the extensor surfaces of the lower legs and dorsal feet.^1,2,7 Lesions also may appear on the extensor surfaces of the arms, pinna, periocular region, antecubital and popliteal fossae, and oral mucosa and also may present as pits on the palms and soles.^2,4,7,8 Furthermore, unilateral and localized variants of HLP have been described.^11,12 Hyperkeratosis lenticularis perstans usually is asymptomatic but can present with mild pruritus or burning.^3,5,13

The etiology and pathogenesis of HLP are unknown. Exposure to UV light has been implicated as an inciting factor¹⁴; however, reports of spontaneous resolution in the summer¹³ and upon treatment with psoralen plus UVA therapy¹⁵ make the role of UV light unclear. Furthermore, investigators disagree as to whether the primary pathogenic event in HLP is an inflammatory process or one of abnormal keratinization.^1,3,7,10 Fernandez-Flores and Manjon¹⁶ suggested HLP is an inflammatory process with periods of exacerbations and remissions after finding mounds of parakeratosis with neutrophils arranged in different strata in the stratum corneum.

Histologically, compact hyperkeratosis usually is noted, often with associated parakeratosis, epidermal atrophy with thinning or absence of the granular layer, and a bandlike lymphohistiocytic infiltrate in the papillary dermis.^1-3 Histopathologic differences between recent-onset versus longstanding lesions have been found, with old lesions lacking an inflammatory infiltrate.³ Furthermore, new lesions often show abnormalities in quantity and/or morphology of membrane-coating granules, also known as Odland bodies, in keratinocytes on electron microscopy,^3,10,17 while old lesions do not.³ Odland bodies are involved in normal desquamation, leading some to speculate on their role in HLP.¹⁰ Currently, it is unclear whether abnormalities in these organelles cause the retention hyperkeratosis seen in HLP or if such abnormalities are a secondary phenomenon.^3,17

There are questionable associations between HLP and diabetes mellitus type 2, hyperthyroidism, basal and squamous cell carcinomas of the skin, and gastrointestinal malignancy.^4,9,18 Our patient had a history of basal cell carcinoma on the face, diet-controlled diabetes mellitus, and hypothyroidism. Given the high prevalence of these diseases in the general population, however, it is difficult to ascertain whether a true association with HLP exists.

While HLP can slowly progress to involve additional body sites, it is overall a benign condition that does not require treatment. Therapeutic options are based on case reports, with no single treatment showing a consistent response. From review of the literature, therapies that have been most effective include dermabrasion, excision,¹⁹ topical 5-fluorouracil,^2,17,20 and oral retinoids.⁸ Hyperkeratosis lenticularis perstans generally is resistant to topical steroids, retinoids, and vitamin D₃ analogs, although success with betamethasone dipropionate,⁵ isotretinoin  
gel 0.05%,¹¹ and calcipotriol have been reported.⁶ A case of HLP with clinical response to psoralen plus UVA therapy also has been described.¹⁵

The Diagnosis: Hyperkeratosis Lenticularis Perstans

A shave biopsy of a lesion on the right leg was performed. Histopathology revealed a discrete papule with overlying compact hyperkeratosis. There was parakeratosis with an absent granular layer and a lichenoid lymphocytic infiltrate within the papillary dermis (Figure). Given the clinical context, these changes were consistent with a diagnosis of hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease.

The patient was started on tretinoin cream 0.1% nightly for 3 months and triamcinolone ointment 0.1% as needed for pruritus but showed no clinical response. Given the benign nature of the condition and because the lesions were asymptomatic, additional treatment options were not pursued.

Originally described by Flegel¹ in 1958, HLP is a rare skin disorder commonly seen in white individuals with onset in the fourth or fifth decades of life.^1,2 While most cases are sporadic,^3-6 HLP also has been associated with autosomal dominant inheritance.^7-10

Patients with HLP typically present with multiple 1- to 5-mm reddish-brown, hyperkeratotic, scaly papules that reveal a moist, erythematous base with pinpoint bleeding upon removal of the scale. Lesions usually are distributed symmetrically and most commonly present on the extensor surfaces of the lower legs and dorsal feet.^1,2,7 Lesions also may appear on the extensor surfaces of the arms, pinna, periocular region, antecubital and popliteal fossae, and oral mucosa and also may present as pits on the palms and soles.^2,4,7,8 Furthermore, unilateral and localized variants of HLP have been described.^11,12 Hyperkeratosis lenticularis perstans usually is asymptomatic but can present with mild pruritus or burning.^3,5,13

The etiology and pathogenesis of HLP are unknown. Exposure to UV light has been implicated as an inciting factor¹⁴; however, reports of spontaneous resolution in the summer¹³ and upon treatment with psoralen plus UVA therapy¹⁵ make the role of UV light unclear. Furthermore, investigators disagree as to whether the primary pathogenic event in HLP is an inflammatory process or one of abnormal keratinization.^1,3,7,10 Fernandez-Flores and Manjon¹⁶ suggested HLP is an inflammatory process with periods of exacerbations and remissions after finding mounds of parakeratosis with neutrophils arranged in different strata in the stratum corneum.

Histologically, compact hyperkeratosis usually is noted, often with associated parakeratosis, epidermal atrophy with thinning or absence of the granular layer, and a bandlike lymphohistiocytic infiltrate in the papillary dermis.^1-3 Histopathologic differences between recent-onset versus longstanding lesions have been found, with old lesions lacking an inflammatory infiltrate.³ Furthermore, new lesions often show abnormalities in quantity and/or morphology of membrane-coating granules, also known as Odland bodies, in keratinocytes on electron microscopy,^3,10,17 while old lesions do not.³ Odland bodies are involved in normal desquamation, leading some to speculate on their role in HLP.¹⁰ Currently, it is unclear whether abnormalities in these organelles cause the retention hyperkeratosis seen in HLP or if such abnormalities are a secondary phenomenon.^3,17

There are questionable associations between HLP and diabetes mellitus type 2, hyperthyroidism, basal and squamous cell carcinomas of the skin, and gastrointestinal malignancy.^4,9,18 Our patient had a history of basal cell carcinoma on the face, diet-controlled diabetes mellitus, and hypothyroidism. Given the high prevalence of these diseases in the general population, however, it is difficult to ascertain whether a true association with HLP exists.

While HLP can slowly progress to involve additional body sites, it is overall a benign condition that does not require treatment. Therapeutic options are based on case reports, with no single treatment showing a consistent response. From review of the literature, therapies that have been most effective include dermabrasion, excision,¹⁹ topical 5-fluorouracil,^2,17,20 and oral retinoids.⁸ Hyperkeratosis lenticularis perstans generally is resistant to topical steroids, retinoids, and vitamin D₃ analogs, although success with betamethasone dipropionate,⁵ isotretinoin  
gel 0.05%,¹¹ and calcipotriol have been reported.⁶ A case of HLP with clinical response to psoralen plus UVA therapy also has been described.¹⁵

The Diagnosis: Hyperkeratosis Lenticularis Perstans

A shave biopsy of a lesion on the right leg was performed. Histopathology revealed a discrete papule with overlying compact hyperkeratosis. There was parakeratosis with an absent granular layer and a lichenoid lymphocytic infiltrate within the papillary dermis (Figure). Given the clinical context, these changes were consistent with a diagnosis of hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease.

The patient was started on tretinoin cream 0.1% nightly for 3 months and triamcinolone ointment 0.1% as needed for pruritus but showed no clinical response. Given the benign nature of the condition and because the lesions were asymptomatic, additional treatment options were not pursued.

Originally described by Flegel¹ in 1958, HLP is a rare skin disorder commonly seen in white individuals with onset in the fourth or fifth decades of life.^1,2 While most cases are sporadic,^3-6 HLP also has been associated with autosomal dominant inheritance.^7-10

Patients with HLP typically present with multiple 1- to 5-mm reddish-brown, hyperkeratotic, scaly papules that reveal a moist, erythematous base with pinpoint bleeding upon removal of the scale. Lesions usually are distributed symmetrically and most commonly present on the extensor surfaces of the lower legs and dorsal feet.^1,2,7 Lesions also may appear on the extensor surfaces of the arms, pinna, periocular region, antecubital and popliteal fossae, and oral mucosa and also may present as pits on the palms and soles.^2,4,7,8 Furthermore, unilateral and localized variants of HLP have been described.^11,12 Hyperkeratosis lenticularis perstans usually is asymptomatic but can present with mild pruritus or burning.^3,5,13

The etiology and pathogenesis of HLP are unknown. Exposure to UV light has been implicated as an inciting factor¹⁴; however, reports of spontaneous resolution in the summer¹³ and upon treatment with psoralen plus UVA therapy¹⁵ make the role of UV light unclear. Furthermore, investigators disagree as to whether the primary pathogenic event in HLP is an inflammatory process or one of abnormal keratinization.^1,3,7,10 Fernandez-Flores and Manjon¹⁶ suggested HLP is an inflammatory process with periods of exacerbations and remissions after finding mounds of parakeratosis with neutrophils arranged in different strata in the stratum corneum.

Histologically, compact hyperkeratosis usually is noted, often with associated parakeratosis, epidermal atrophy with thinning or absence of the granular layer, and a bandlike lymphohistiocytic infiltrate in the papillary dermis.^1-3 Histopathologic differences between recent-onset versus longstanding lesions have been found, with old lesions lacking an inflammatory infiltrate.³ Furthermore, new lesions often show abnormalities in quantity and/or morphology of membrane-coating granules, also known as Odland bodies, in keratinocytes on electron microscopy,^3,10,17 while old lesions do not.³ Odland bodies are involved in normal desquamation, leading some to speculate on their role in HLP.¹⁰ Currently, it is unclear whether abnormalities in these organelles cause the retention hyperkeratosis seen in HLP or if such abnormalities are a secondary phenomenon.^3,17

There are questionable associations between HLP and diabetes mellitus type 2, hyperthyroidism, basal and squamous cell carcinomas of the skin, and gastrointestinal malignancy.^4,9,18 Our patient had a history of basal cell carcinoma on the face, diet-controlled diabetes mellitus, and hypothyroidism. Given the high prevalence of these diseases in the general population, however, it is difficult to ascertain whether a true association with HLP exists.

While HLP can slowly progress to involve additional body sites, it is overall a benign condition that does not require treatment. Therapeutic options are based on case reports, with no single treatment showing a consistent response. From review of the literature, therapies that have been most effective include dermabrasion, excision,¹⁹ topical 5-fluorouracil,^2,17,20 and oral retinoids.⁸ Hyperkeratosis lenticularis perstans generally is resistant to topical steroids, retinoids, and vitamin D₃ analogs, although success with betamethasone dipropionate,⁵ isotretinoin  
gel 0.05%,¹¹ and calcipotriol have been reported.⁶ A case of HLP with clinical response to psoralen plus UVA therapy also has been described.¹⁵

The Diagnosis: Herpes Zoster

Herpes zoster is a common infection that clinically presents with moderate to intense pain in the involved dermatome (1–3 days before the outbreak¹) followed by a unilateral dermatomal eruption. The most common sites of involvement include the trunk (dermatomes T3–L2) and upper face (dermatome V1).² Herpes zoster characteristically begins as erythematous macules and papules that progress to vesicles and sometimes pustules, which subsequently crust over (7–10 days after the initial outbreak).¹ Regional lymphadenopathy is present in most cases. Due to the classic presentation of herpes zoster, clinical diagnosis is the mainstay for most cases. Although it can present in any age group, herpes zoster is most commonly associated with advancing age.³

During the course of primary varicella infection, the herpes virus spreads from infected lesions to the contiguous endings of sensory nerves and travels to the dorsal root ganglion cells where it remains latent.¹ It is hypothesized that cell-mediated immunity suppresses viral activity and maintains viral latency. A decline in varicella zoster virus–specific cell-mediated immunity can result in reactivation of the latent virus.¹ The virus is then transported to the skin from the dorsal root ganglion via myelinated nerves, which terminate at the isthmus of hair follicles, and subsequent infection of the folliculosebaceous unit occurs.⁴

Laboratory tests that can assist in the diagnosis of herpes zoster, especially atypical cases, include Tzanck smear and viral culture of the vesicle fluid.¹ When vesicles are not present, biopsy of the lesion followed by immunohistochemical staining and polymerase chain reaction assay can aid in the diagnosis. The differential diagnosis for our patient included pseudolymphoma, herpes simplex virus, lymphomatoid papulosis, sarcoidosis, trigeminal trophic syndrome, and Sweet syndrome.

Vesicles were not present in our patient, but the dermatomal nature of the eruption and the pain she experienced made the clinical scenario suspicious for herpes zoster. A 4-mm punch biopsy of a single folliculosebaceous unit revealed herpetic, cytopathic features including prominent keratinocyte necrosis involving sebaceous, isthmic, and infundibular epithelium; ballooning of epithelial cells with steel gray nuclei; and multinucleation with nuclear molding (Figure 1). Strong nuclear and cytoplasmic staining was seen in the affected keratinocytes under anti–varicella zoster virus immunohistochemical analysis (Figure 2). Staining for herpes simplex virus types 1 and 2 was negative. Within days of starting valacyclovir 1000 mg (every 8 hours for 1 week), the patient’s symptoms resolved.
 

Atypical presentations of herpes zoster (eg, presentations that are not completely dermatomal) are becoming more common. Herpetic infections should always be in the differential diagnosis for cutaneous ulcerations. Misdiagnosis of herpes zoster due to atypical features is common and can delay prompt and adequate treatment.

The Diagnosis: Herpes Zoster

Herpes zoster is a common infection that clinically presents with moderate to intense pain in the involved dermatome (1–3 days before the outbreak¹) followed by a unilateral dermatomal eruption. The most common sites of involvement include the trunk (dermatomes T3–L2) and upper face (dermatome V1).² Herpes zoster characteristically begins as erythematous macules and papules that progress to vesicles and sometimes pustules, which subsequently crust over (7–10 days after the initial outbreak).¹ Regional lymphadenopathy is present in most cases. Due to the classic presentation of herpes zoster, clinical diagnosis is the mainstay for most cases. Although it can present in any age group, herpes zoster is most commonly associated with advancing age.³

During the course of primary varicella infection, the herpes virus spreads from infected lesions to the contiguous endings of sensory nerves and travels to the dorsal root ganglion cells where it remains latent.¹ It is hypothesized that cell-mediated immunity suppresses viral activity and maintains viral latency. A decline in varicella zoster virus–specific cell-mediated immunity can result in reactivation of the latent virus.¹ The virus is then transported to the skin from the dorsal root ganglion via myelinated nerves, which terminate at the isthmus of hair follicles, and subsequent infection of the folliculosebaceous unit occurs.⁴

Laboratory tests that can assist in the diagnosis of herpes zoster, especially atypical cases, include Tzanck smear and viral culture of the vesicle fluid.¹ When vesicles are not present, biopsy of the lesion followed by immunohistochemical staining and polymerase chain reaction assay can aid in the diagnosis. The differential diagnosis for our patient included pseudolymphoma, herpes simplex virus, lymphomatoid papulosis, sarcoidosis, trigeminal trophic syndrome, and Sweet syndrome.

Vesicles were not present in our patient, but the dermatomal nature of the eruption and the pain she experienced made the clinical scenario suspicious for herpes zoster. A 4-mm punch biopsy of a single folliculosebaceous unit revealed herpetic, cytopathic features including prominent keratinocyte necrosis involving sebaceous, isthmic, and infundibular epithelium; ballooning of epithelial cells with steel gray nuclei; and multinucleation with nuclear molding (Figure 1). Strong nuclear and cytoplasmic staining was seen in the affected keratinocytes under anti–varicella zoster virus immunohistochemical analysis (Figure 2). Staining for herpes simplex virus types 1 and 2 was negative. Within days of starting valacyclovir 1000 mg (every 8 hours for 1 week), the patient’s symptoms resolved.
 

Atypical presentations of herpes zoster (eg, presentations that are not completely dermatomal) are becoming more common. Herpetic infections should always be in the differential diagnosis for cutaneous ulcerations. Misdiagnosis of herpes zoster due to atypical features is common and can delay prompt and adequate treatment.

The Diagnosis: Herpes Zoster

Herpes zoster is a common infection that clinically presents with moderate to intense pain in the involved dermatome (1–3 days before the outbreak¹) followed by a unilateral dermatomal eruption. The most common sites of involvement include the trunk (dermatomes T3–L2) and upper face (dermatome V1).² Herpes zoster characteristically begins as erythematous macules and papules that progress to vesicles and sometimes pustules, which subsequently crust over (7–10 days after the initial outbreak).¹ Regional lymphadenopathy is present in most cases. Due to the classic presentation of herpes zoster, clinical diagnosis is the mainstay for most cases. Although it can present in any age group, herpes zoster is most commonly associated with advancing age.³

During the course of primary varicella infection, the herpes virus spreads from infected lesions to the contiguous endings of sensory nerves and travels to the dorsal root ganglion cells where it remains latent.¹ It is hypothesized that cell-mediated immunity suppresses viral activity and maintains viral latency. A decline in varicella zoster virus–specific cell-mediated immunity can result in reactivation of the latent virus.¹ The virus is then transported to the skin from the dorsal root ganglion via myelinated nerves, which terminate at the isthmus of hair follicles, and subsequent infection of the folliculosebaceous unit occurs.⁴

Laboratory tests that can assist in the diagnosis of herpes zoster, especially atypical cases, include Tzanck smear and viral culture of the vesicle fluid.¹ When vesicles are not present, biopsy of the lesion followed by immunohistochemical staining and polymerase chain reaction assay can aid in the diagnosis. The differential diagnosis for our patient included pseudolymphoma, herpes simplex virus, lymphomatoid papulosis, sarcoidosis, trigeminal trophic syndrome, and Sweet syndrome.

Vesicles were not present in our patient, but the dermatomal nature of the eruption and the pain she experienced made the clinical scenario suspicious for herpes zoster. A 4-mm punch biopsy of a single folliculosebaceous unit revealed herpetic, cytopathic features including prominent keratinocyte necrosis involving sebaceous, isthmic, and infundibular epithelium; ballooning of epithelial cells with steel gray nuclei; and multinucleation with nuclear molding (Figure 1). Strong nuclear and cytoplasmic staining was seen in the affected keratinocytes under anti–varicella zoster virus immunohistochemical analysis (Figure 2). Staining for herpes simplex virus types 1 and 2 was negative. Within days of starting valacyclovir 1000 mg (every 8 hours for 1 week), the patient’s symptoms resolved.
 

Atypical presentations of herpes zoster (eg, presentations that are not completely dermatomal) are becoming more common. Herpetic infections should always be in the differential diagnosis for cutaneous ulcerations. Misdiagnosis of herpes zoster due to atypical features is common and can delay prompt and adequate treatment.

The Diagnosis: Acrodermatitis Continua of Hallopeau

Acrodermatitis continua of Hallopeau (ACH) is considered to be a form of acropustular psoriasis that presents as a sterile, pustular eruption initially affecting the fingertips and/or toes.¹ The slow-growing pustules typically progress locally and can lead to onychodystrophy and/or osteolysis of the underlying bone.^2,3 Most commonly affecting adult women, ACH often begins following local trauma to or infection of a single digit.⁴ As the disease progresses proximally, the small pustules burst, leaving a shiny, erythematous surface on which new pustules can develop. These pustules have a tendency to amalgamate, leading to the characteristic clinical finding of lakes of pus. Pustules frequently appear on the nail matrix and nail bed presenting as severe onychodystrophy and ultimately anonychia.^5,6 Rarely, ACH can be associated with generalized pustular psoriasis as well as conjunctivitis, balanitis, and fissuring or annulus migrans of the tongue.^2,7

Diagnosis can be established based on clinical findings, biopsy, and bacterial and fungal cultures revealing sterile pustules.^8,9 Histologic findings are similar to those seen in pustular psoriasis, demonstrating subcorneal neutrophilic pustules, Munro microabscesses, and dilated blood vessels with lymphocytic infiltrate in the papillary dermis.¹⁰

Due to the refractory nature of the disease, there are no recommended guidelines for treatment of ACH. Most successful treatment regimens consist of topical psoriasis medications combined with systemic psoriatic therapies such as cyclosporine, methotrexate, acitretin, or biologic therapy.^8,11-16 Our patient achieved satisfactory clinical improvement with clobetasol propionate ointment 0.05% twice daily alternating with calcipotriene cream 0.005% twice daily.

The Diagnosis: Acrodermatitis Continua of Hallopeau

Acrodermatitis continua of Hallopeau (ACH) is considered to be a form of acropustular psoriasis that presents as a sterile, pustular eruption initially affecting the fingertips and/or toes.¹ The slow-growing pustules typically progress locally and can lead to onychodystrophy and/or osteolysis of the underlying bone.^2,3 Most commonly affecting adult women, ACH often begins following local trauma to or infection of a single digit.⁴ As the disease progresses proximally, the small pustules burst, leaving a shiny, erythematous surface on which new pustules can develop. These pustules have a tendency to amalgamate, leading to the characteristic clinical finding of lakes of pus. Pustules frequently appear on the nail matrix and nail bed presenting as severe onychodystrophy and ultimately anonychia.^5,6 Rarely, ACH can be associated with generalized pustular psoriasis as well as conjunctivitis, balanitis, and fissuring or annulus migrans of the tongue.^2,7

Diagnosis can be established based on clinical findings, biopsy, and bacterial and fungal cultures revealing sterile pustules.^8,9 Histologic findings are similar to those seen in pustular psoriasis, demonstrating subcorneal neutrophilic pustules, Munro microabscesses, and dilated blood vessels with lymphocytic infiltrate in the papillary dermis.¹⁰

Due to the refractory nature of the disease, there are no recommended guidelines for treatment of ACH. Most successful treatment regimens consist of topical psoriasis medications combined with systemic psoriatic therapies such as cyclosporine, methotrexate, acitretin, or biologic therapy.^8,11-16 Our patient achieved satisfactory clinical improvement with clobetasol propionate ointment 0.05% twice daily alternating with calcipotriene cream 0.005% twice daily.

The Diagnosis: Acrodermatitis Continua of Hallopeau

Acrodermatitis continua of Hallopeau (ACH) is considered to be a form of acropustular psoriasis that presents as a sterile, pustular eruption initially affecting the fingertips and/or toes.¹ The slow-growing pustules typically progress locally and can lead to onychodystrophy and/or osteolysis of the underlying bone.^2,3 Most commonly affecting adult women, ACH often begins following local trauma to or infection of a single digit.⁴ As the disease progresses proximally, the small pustules burst, leaving a shiny, erythematous surface on which new pustules can develop. These pustules have a tendency to amalgamate, leading to the characteristic clinical finding of lakes of pus. Pustules frequently appear on the nail matrix and nail bed presenting as severe onychodystrophy and ultimately anonychia.^5,6 Rarely, ACH can be associated with generalized pustular psoriasis as well as conjunctivitis, balanitis, and fissuring or annulus migrans of the tongue.^2,7

Diagnosis can be established based on clinical findings, biopsy, and bacterial and fungal cultures revealing sterile pustules.^8,9 Histologic findings are similar to those seen in pustular psoriasis, demonstrating subcorneal neutrophilic pustules, Munro microabscesses, and dilated blood vessels with lymphocytic infiltrate in the papillary dermis.¹⁰

Due to the refractory nature of the disease, there are no recommended guidelines for treatment of ACH. Most successful treatment regimens consist of topical psoriasis medications combined with systemic psoriatic therapies such as cyclosporine, methotrexate, acitretin, or biologic therapy.^8,11-16 Our patient achieved satisfactory clinical improvement with clobetasol propionate ointment 0.05% twice daily alternating with calcipotriene cream 0.005% twice daily.

The Diagnosis: Tinea Corporis

Although contact dermatitis from the metal on the back of the watch was suspected, many modern wrist watches are made with stainless steel rather than nickel, which is a common contact allergen; therefore, other diagnoses were considered in the differential including irritant contact dermatitis, psoriasis, and tinea infection. A potassium hydroxide (KOH) preparation was performed to rule out tinea infection. Unexpectedly, the KOH preparation was positive for fungal hyphae, confirming a diagnosis of tinea corporis. The patient was treated with clotrimazole cream 1% twice daily for 3 weeks during which time the rash completely resolved.

We present this case to stress the importance of performing KOH preparations even when the likelihood of tinea infection seems remote. At our institution, we teach our residents, “If it’s scaly, scrape it.” This adage has served us well. Tinea corporis may be mistaken for many other skin diseases, including eczema, psoriasis, and seborrheic dermatitis.¹ A KOH preparation often is a helpful tool in confirming the diagnosis and should be performed when a dermatophyte infection is suspected. The KOH preparation is the most sensitive diagnostic test used to confirm dermatophyte infection, with 90% of infections showing positive results.^2,3

Tinea infections may occur anywhere on the body, but areas that are prone to excessive heat and/or moisture are particularly susceptible.⁴ Dermatophyte infections typically present as annular, scaly, pruritic patches or plaques often with central clearing and an active border.¹ In our patient, the lesion showed characteristics that were suggestive of a dermatophyte infection but was somewhat atypical in appearance, as it lacked central clearing (Figure). The 3 genera of dermatophytes—Trichophyton, Microsporum, and Epidermophyton—are common causes of fungal infections.² The pathogenesis of dermatophytosis is the synthesis of keratinases that digest keratin and sustain the presence of the fungi. Local factors such as sweating and occlusion facilitate the activity of these organisms.² In our case, the pathogenesis was believed to be due to the entrapment of moisture behind the patient’s watch, creating a favorable environment for fungal growth.

The Diagnosis: Tinea Corporis

Although contact dermatitis from the metal on the back of the watch was suspected, many modern wrist watches are made with stainless steel rather than nickel, which is a common contact allergen; therefore, other diagnoses were considered in the differential including irritant contact dermatitis, psoriasis, and tinea infection. A potassium hydroxide (KOH) preparation was performed to rule out tinea infection. Unexpectedly, the KOH preparation was positive for fungal hyphae, confirming a diagnosis of tinea corporis. The patient was treated with clotrimazole cream 1% twice daily for 3 weeks during which time the rash completely resolved.

We present this case to stress the importance of performing KOH preparations even when the likelihood of tinea infection seems remote. At our institution, we teach our residents, “If it’s scaly, scrape it.” This adage has served us well. Tinea corporis may be mistaken for many other skin diseases, including eczema, psoriasis, and seborrheic dermatitis.¹ A KOH preparation often is a helpful tool in confirming the diagnosis and should be performed when a dermatophyte infection is suspected. The KOH preparation is the most sensitive diagnostic test used to confirm dermatophyte infection, with 90% of infections showing positive results.^2,3

Tinea infections may occur anywhere on the body, but areas that are prone to excessive heat and/or moisture are particularly susceptible.⁴ Dermatophyte infections typically present as annular, scaly, pruritic patches or plaques often with central clearing and an active border.¹ In our patient, the lesion showed characteristics that were suggestive of a dermatophyte infection but was somewhat atypical in appearance, as it lacked central clearing (Figure). The 3 genera of dermatophytes—Trichophyton, Microsporum, and Epidermophyton—are common causes of fungal infections.² The pathogenesis of dermatophytosis is the synthesis of keratinases that digest keratin and sustain the presence of the fungi. Local factors such as sweating and occlusion facilitate the activity of these organisms.² In our case, the pathogenesis was believed to be due to the entrapment of moisture behind the patient’s watch, creating a favorable environment for fungal growth.

The Diagnosis: Tinea Corporis

Although contact dermatitis from the metal on the back of the watch was suspected, many modern wrist watches are made with stainless steel rather than nickel, which is a common contact allergen; therefore, other diagnoses were considered in the differential including irritant contact dermatitis, psoriasis, and tinea infection. A potassium hydroxide (KOH) preparation was performed to rule out tinea infection. Unexpectedly, the KOH preparation was positive for fungal hyphae, confirming a diagnosis of tinea corporis. The patient was treated with clotrimazole cream 1% twice daily for 3 weeks during which time the rash completely resolved.

We present this case to stress the importance of performing KOH preparations even when the likelihood of tinea infection seems remote. At our institution, we teach our residents, “If it’s scaly, scrape it.” This adage has served us well. Tinea corporis may be mistaken for many other skin diseases, including eczema, psoriasis, and seborrheic dermatitis.¹ A KOH preparation often is a helpful tool in confirming the diagnosis and should be performed when a dermatophyte infection is suspected. The KOH preparation is the most sensitive diagnostic test used to confirm dermatophyte infection, with 90% of infections showing positive results.^2,3

Tinea infections may occur anywhere on the body, but areas that are prone to excessive heat and/or moisture are particularly susceptible.⁴ Dermatophyte infections typically present as annular, scaly, pruritic patches or plaques often with central clearing and an active border.¹ In our patient, the lesion showed characteristics that were suggestive of a dermatophyte infection but was somewhat atypical in appearance, as it lacked central clearing (Figure). The 3 genera of dermatophytes—Trichophyton, Microsporum, and Epidermophyton—are common causes of fungal infections.² The pathogenesis of dermatophytosis is the synthesis of keratinases that digest keratin and sustain the presence of the fungi. Local factors such as sweating and occlusion facilitate the activity of these organisms.² In our case, the pathogenesis was believed to be due to the entrapment of moisture behind the patient’s watch, creating a favorable environment for fungal growth.

The Diagnosis: Agminated Blue Nevus

Agminated blue nevus is a rare melanocytic nevus that characteristically presents as a group of multiple small, bluish papules occurring in a well-circumscribed area.¹ It also has been referred to as a plaque-type nevus^2,3 and an eruptive blue nevus.⁴ Originally described by Upshaw et al² in 1947, agminated blue nevi may be congenital or arise in early childhood and almost always occur on the trunk. The skin between the papules often is unaffected or sometimes may show bluish or brown pigmentation.⁴ Agminated blue nevi usually are smaller than 10 cm in diameter; however, rare cases have measured up to 24 cm.^1,4-6 The incidence of agminated blue nevi is 2 times higher in males than in females.¹

A biopsy of the lesion revealed pigmented dendritic melanocytes admixed with melanophages, forming fascicles and bundles (A)(H&E, original magnification ×10). In some areas the dermis was uninvolved. Higher magnification showed dendritic and epithelioid melanocytes extending down along the adnexal structures (B)(H&E, original magnification ×40).

Histopathologically, agminated blue nevi typically demonstrate the features of common and/or cellular blue nevi. Cytologic atypia and mitoses are rare.¹ The degree of cellularity and pigmentation of the lesions is variable, and the presence of subcutaneous cellular nodules also has been described.⁵

In our patient, histologic evaluation revealed foci of diffuse dermal spindle cell proliferation composed of heavily pigmented dendritic melanocytes admixed with melanophages in a fibrotic stroma (Figure, A). The dermis was uninvolved in some areas and the melanocytes were epithelioid and formed fascicles and bundles that extended down adnexal structures in other areas (Figure, B). Junctional involvement of melanocytes, cellular atypia, and mitoses were not identified. Our case demonstrated a combination of histologic findings of a cellular blue nevus as well as features reminiscent of a deep penetrating nevus. The differential diagnosis of agminated blue nevus includes agminated Spitz nevus arising in a speckled lentiginous nevus,⁷ dermal melanocytosis, melanoma, and pilar neurocristic hamartoma. Pilar neurocristic hamartomas may resemble plaque-type blue nevi; however, the former show a predilection for the scalp, histologically demonstrate features that overlap with blue nevi and congenital nevi, and are associated with neural structures that show Schwannian differentiation.⁸ Agminated blue nevi usually are characterized by a benign clinical course, but few cases describing malignant changes with development of malignant melanoma have been reported.^9,10 Therefore, recognition of the clinical and histopathologic spectrum of agminated blue nevus is critical in order to avoid diagnostic pitfalls and confusion with melanoma.

The Diagnosis: Agminated Blue Nevus

Agminated blue nevus is a rare melanocytic nevus that characteristically presents as a group of multiple small, bluish papules occurring in a well-circumscribed area.¹ It also has been referred to as a plaque-type nevus^2,3 and an eruptive blue nevus.⁴ Originally described by Upshaw et al² in 1947, agminated blue nevi may be congenital or arise in early childhood and almost always occur on the trunk. The skin between the papules often is unaffected or sometimes may show bluish or brown pigmentation.⁴ Agminated blue nevi usually are smaller than 10 cm in diameter; however, rare cases have measured up to 24 cm.^1,4-6 The incidence of agminated blue nevi is 2 times higher in males than in females.¹

A biopsy of the lesion revealed pigmented dendritic melanocytes admixed with melanophages, forming fascicles and bundles (A)(H&E, original magnification ×10). In some areas the dermis was uninvolved. Higher magnification showed dendritic and epithelioid melanocytes extending down along the adnexal structures (B)(H&E, original magnification ×40).

Histopathologically, agminated blue nevi typically demonstrate the features of common and/or cellular blue nevi. Cytologic atypia and mitoses are rare.¹ The degree of cellularity and pigmentation of the lesions is variable, and the presence of subcutaneous cellular nodules also has been described.⁵

In our patient, histologic evaluation revealed foci of diffuse dermal spindle cell proliferation composed of heavily pigmented dendritic melanocytes admixed with melanophages in a fibrotic stroma (Figure, A). The dermis was uninvolved in some areas and the melanocytes were epithelioid and formed fascicles and bundles that extended down adnexal structures in other areas (Figure, B). Junctional involvement of melanocytes, cellular atypia, and mitoses were not identified. Our case demonstrated a combination of histologic findings of a cellular blue nevus as well as features reminiscent of a deep penetrating nevus. The differential diagnosis of agminated blue nevus includes agminated Spitz nevus arising in a speckled lentiginous nevus,⁷ dermal melanocytosis, melanoma, and pilar neurocristic hamartoma. Pilar neurocristic hamartomas may resemble plaque-type blue nevi; however, the former show a predilection for the scalp, histologically demonstrate features that overlap with blue nevi and congenital nevi, and are associated with neural structures that show Schwannian differentiation.⁸ Agminated blue nevi usually are characterized by a benign clinical course, but few cases describing malignant changes with development of malignant melanoma have been reported.^9,10 Therefore, recognition of the clinical and histopathologic spectrum of agminated blue nevus is critical in order to avoid diagnostic pitfalls and confusion with melanoma.

The Diagnosis: Agminated Blue Nevus

Agminated blue nevus is a rare melanocytic nevus that characteristically presents as a group of multiple small, bluish papules occurring in a well-circumscribed area.¹ It also has been referred to as a plaque-type nevus^2,3 and an eruptive blue nevus.⁴ Originally described by Upshaw et al² in 1947, agminated blue nevi may be congenital or arise in early childhood and almost always occur on the trunk. The skin between the papules often is unaffected or sometimes may show bluish or brown pigmentation.⁴ Agminated blue nevi usually are smaller than 10 cm in diameter; however, rare cases have measured up to 24 cm.^1,4-6 The incidence of agminated blue nevi is 2 times higher in males than in females.¹

A biopsy of the lesion revealed pigmented dendritic melanocytes admixed with melanophages, forming fascicles and bundles (A)(H&E, original magnification ×10). In some areas the dermis was uninvolved. Higher magnification showed dendritic and epithelioid melanocytes extending down along the adnexal structures (B)(H&E, original magnification ×40).

Histopathologically, agminated blue nevi typically demonstrate the features of common and/or cellular blue nevi. Cytologic atypia and mitoses are rare.¹ The degree of cellularity and pigmentation of the lesions is variable, and the presence of subcutaneous cellular nodules also has been described.⁵

In our patient, histologic evaluation revealed foci of diffuse dermal spindle cell proliferation composed of heavily pigmented dendritic melanocytes admixed with melanophages in a fibrotic stroma (Figure, A). The dermis was uninvolved in some areas and the melanocytes were epithelioid and formed fascicles and bundles that extended down adnexal structures in other areas (Figure, B). Junctional involvement of melanocytes, cellular atypia, and mitoses were not identified. Our case demonstrated a combination of histologic findings of a cellular blue nevus as well as features reminiscent of a deep penetrating nevus. The differential diagnosis of agminated blue nevus includes agminated Spitz nevus arising in a speckled lentiginous nevus,⁷ dermal melanocytosis, melanoma, and pilar neurocristic hamartoma. Pilar neurocristic hamartomas may resemble plaque-type blue nevi; however, the former show a predilection for the scalp, histologically demonstrate features that overlap with blue nevi and congenital nevi, and are associated with neural structures that show Schwannian differentiation.⁸ Agminated blue nevi usually are characterized by a benign clinical course, but few cases describing malignant changes with development of malignant melanoma have been reported.^9,10 Therefore, recognition of the clinical and histopathologic spectrum of agminated blue nevus is critical in order to avoid diagnostic pitfalls and confusion with melanoma.

The Diagnosis: Eccrine Poroma

A shave biopsy of the lesion was performed for definitive diagnosis and demonstrated a well-circumscribed tumor with cords and broad columns composed of uniform basaloid cells extending into the dermis and in areas connecting to the overlying epidermis (Figure). There also were small ducts and cysts admixed in the tumor columns that were embedded in a tumor stroma rich in blood vessels. A diagnosis of eccrine poroma was made based on these characteristic histologic features.

Biopsy revealed a basaloid tumor originating from the epidermis and extending into the dermis (A)(H&E, original magnification ×4). On higher magnification, ducts were evident amongst the tumor cells and a vascular rich stroma was revealed (B)(H&E, original magnification ×10).

First described by Pinkus et al¹ in 1956, eccrine poroma is a benign neoplasm of cells from the intraepidermal ductal portion of the eccrine sweat gland. Eccrine poroma (along with hidroacanthoma simplex, dermal duct tumor, and poroid hidradenoma) is one of the poroid neoplasms, which account for approximately 10% of all primary sweat gland tumors.² Eccrine poroma usually is seen in patients over 40 years of age without any predilection for race or sex.

Characteristically, eccrine poromas clinically manifest as solitary, firm, sharply demarcated papules or nodules that may be sessile or pedunculated and rarely exceed 2 cm in diameter. This entity classically presents on acral, non–hair-bearing areas (eg, palms and soles). Eccrine poromas have a wide range of clinical appearances that can lead to broad differential diagnoses³ and have been described as flesh-colored,³ pink to red,⁴ purple,⁵ and pigmented^3,4 papules or nodules depending on features such as blood vessel proliferation and pigment deposition.

Eccrine poromas also have been reported on hair-bearing areas of the body, including the head,³ neck,^3,6 chest,^4,6 hip,⁷ and pubic area,⁸ despite the paucity of eccrine glands in these areas on the body. These findings suggest that these neoplasms may not be purely eccrine in origin. The wide range of clinical presentations of eccrine poromas has prompted investigation into further classification and delineation of this neoplasm.³ The occurrence of eccrine poromas on areas of the skin known to have few eccrine glands suggests that eccrine poromas may not be purely comprised of eccrine ducts and instead may be of apocrine origin.^3,9,10 Histologic features of eccrine poromas that suggest apocrine origination include sebaceous and follicular differentiation (eg, folliculocentric distribution), the association with the follicular infundibulum, and the presence of follicular germ cells.^3,9,10 Thus, apocrine gland involvement in eccrine poromas may account for their appearance in anatomic areas that do not have high concentrations of eccrine glands, such as the trunk and pubic area.

Based on these findings, eccrine poromas may therefore be of eccrine and/or apocrine origin; however, the nomenclature of this neoplasm remains confusing and possibly misleading, as the term eccrine poroma continues to be accepted even in instances in which the differentiation appears to be largely apocrine. The terms poroma and eccrine poroma often are used interchangeably, which contributes to the confusion by failing to acknowledge the possibility of apocrine influence and possibly causing the clinician to exclude eccrine poromas from the differential diagnosis in areas that do not have high concentrations of eccrine glands.

Because of their high degree of clinical variability, characteristic acral location, and misleading nomenclature, eccrine poromas often are mistakenly confused with a long list of other cutaneous neoplasms, including hemangiomas, pyogenic granulomas, melanocytic nevi, warts, cysts, and other adnexal neoplasms.³ In our case, the lesion was abnormally large and was clinically concerning for an unusual sebaceous nevus. Its location on the lower back is not commonly noted and should remind the clinician of the possibility of apocrine differentiation. Clinicians should be aware of the wide phenotypic diversity of eccrine poromas, and therefore they should consider this diagnosis in their differential diagnosis for solitary papules or nodules occurring in any anatomic area.

The Diagnosis: Eccrine Poroma

A shave biopsy of the lesion was performed for definitive diagnosis and demonstrated a well-circumscribed tumor with cords and broad columns composed of uniform basaloid cells extending into the dermis and in areas connecting to the overlying epidermis (Figure). There also were small ducts and cysts admixed in the tumor columns that were embedded in a tumor stroma rich in blood vessels. A diagnosis of eccrine poroma was made based on these characteristic histologic features.

Biopsy revealed a basaloid tumor originating from the epidermis and extending into the dermis (A)(H&E, original magnification ×4). On higher magnification, ducts were evident amongst the tumor cells and a vascular rich stroma was revealed (B)(H&E, original magnification ×10).

First described by Pinkus et al¹ in 1956, eccrine poroma is a benign neoplasm of cells from the intraepidermal ductal portion of the eccrine sweat gland. Eccrine poroma (along with hidroacanthoma simplex, dermal duct tumor, and poroid hidradenoma) is one of the poroid neoplasms, which account for approximately 10% of all primary sweat gland tumors.² Eccrine poroma usually is seen in patients over 40 years of age without any predilection for race or sex.

Characteristically, eccrine poromas clinically manifest as solitary, firm, sharply demarcated papules or nodules that may be sessile or pedunculated and rarely exceed 2 cm in diameter. This entity classically presents on acral, non–hair-bearing areas (eg, palms and soles). Eccrine poromas have a wide range of clinical appearances that can lead to broad differential diagnoses³ and have been described as flesh-colored,³ pink to red,⁴ purple,⁵ and pigmented^3,4 papules or nodules depending on features such as blood vessel proliferation and pigment deposition.

Eccrine poromas also have been reported on hair-bearing areas of the body, including the head,³ neck,^3,6 chest,^4,6 hip,⁷ and pubic area,⁸ despite the paucity of eccrine glands in these areas on the body. These findings suggest that these neoplasms may not be purely eccrine in origin. The wide range of clinical presentations of eccrine poromas has prompted investigation into further classification and delineation of this neoplasm.³ The occurrence of eccrine poromas on areas of the skin known to have few eccrine glands suggests that eccrine poromas may not be purely comprised of eccrine ducts and instead may be of apocrine origin.^3,9,10 Histologic features of eccrine poromas that suggest apocrine origination include sebaceous and follicular differentiation (eg, folliculocentric distribution), the association with the follicular infundibulum, and the presence of follicular germ cells.^3,9,10 Thus, apocrine gland involvement in eccrine poromas may account for their appearance in anatomic areas that do not have high concentrations of eccrine glands, such as the trunk and pubic area.

Based on these findings, eccrine poromas may therefore be of eccrine and/or apocrine origin; however, the nomenclature of this neoplasm remains confusing and possibly misleading, as the term eccrine poroma continues to be accepted even in instances in which the differentiation appears to be largely apocrine. The terms poroma and eccrine poroma often are used interchangeably, which contributes to the confusion by failing to acknowledge the possibility of apocrine influence and possibly causing the clinician to exclude eccrine poromas from the differential diagnosis in areas that do not have high concentrations of eccrine glands.

Because of their high degree of clinical variability, characteristic acral location, and misleading nomenclature, eccrine poromas often are mistakenly confused with a long list of other cutaneous neoplasms, including hemangiomas, pyogenic granulomas, melanocytic nevi, warts, cysts, and other adnexal neoplasms.³ In our case, the lesion was abnormally large and was clinically concerning for an unusual sebaceous nevus. Its location on the lower back is not commonly noted and should remind the clinician of the possibility of apocrine differentiation. Clinicians should be aware of the wide phenotypic diversity of eccrine poromas, and therefore they should consider this diagnosis in their differential diagnosis for solitary papules or nodules occurring in any anatomic area.

The Diagnosis: Eccrine Poroma

A shave biopsy of the lesion was performed for definitive diagnosis and demonstrated a well-circumscribed tumor with cords and broad columns composed of uniform basaloid cells extending into the dermis and in areas connecting to the overlying epidermis (Figure). There also were small ducts and cysts admixed in the tumor columns that were embedded in a tumor stroma rich in blood vessels. A diagnosis of eccrine poroma was made based on these characteristic histologic features.

Biopsy revealed a basaloid tumor originating from the epidermis and extending into the dermis (A)(H&E, original magnification ×4). On higher magnification, ducts were evident amongst the tumor cells and a vascular rich stroma was revealed (B)(H&E, original magnification ×10).

First described by Pinkus et al¹ in 1956, eccrine poroma is a benign neoplasm of cells from the intraepidermal ductal portion of the eccrine sweat gland. Eccrine poroma (along with hidroacanthoma simplex, dermal duct tumor, and poroid hidradenoma) is one of the poroid neoplasms, which account for approximately 10% of all primary sweat gland tumors.² Eccrine poroma usually is seen in patients over 40 years of age without any predilection for race or sex.

Characteristically, eccrine poromas clinically manifest as solitary, firm, sharply demarcated papules or nodules that may be sessile or pedunculated and rarely exceed 2 cm in diameter. This entity classically presents on acral, non–hair-bearing areas (eg, palms and soles). Eccrine poromas have a wide range of clinical appearances that can lead to broad differential diagnoses³ and have been described as flesh-colored,³ pink to red,⁴ purple,⁵ and pigmented^3,4 papules or nodules depending on features such as blood vessel proliferation and pigment deposition.

Eccrine poromas also have been reported on hair-bearing areas of the body, including the head,³ neck,^3,6 chest,^4,6 hip,⁷ and pubic area,⁸ despite the paucity of eccrine glands in these areas on the body. These findings suggest that these neoplasms may not be purely eccrine in origin. The wide range of clinical presentations of eccrine poromas has prompted investigation into further classification and delineation of this neoplasm.³ The occurrence of eccrine poromas on areas of the skin known to have few eccrine glands suggests that eccrine poromas may not be purely comprised of eccrine ducts and instead may be of apocrine origin.^3,9,10 Histologic features of eccrine poromas that suggest apocrine origination include sebaceous and follicular differentiation (eg, folliculocentric distribution), the association with the follicular infundibulum, and the presence of follicular germ cells.^3,9,10 Thus, apocrine gland involvement in eccrine poromas may account for their appearance in anatomic areas that do not have high concentrations of eccrine glands, such as the trunk and pubic area.

Based on these findings, eccrine poromas may therefore be of eccrine and/or apocrine origin; however, the nomenclature of this neoplasm remains confusing and possibly misleading, as the term eccrine poroma continues to be accepted even in instances in which the differentiation appears to be largely apocrine. The terms poroma and eccrine poroma often are used interchangeably, which contributes to the confusion by failing to acknowledge the possibility of apocrine influence and possibly causing the clinician to exclude eccrine poromas from the differential diagnosis in areas that do not have high concentrations of eccrine glands.

Because of their high degree of clinical variability, characteristic acral location, and misleading nomenclature, eccrine poromas often are mistakenly confused with a long list of other cutaneous neoplasms, including hemangiomas, pyogenic granulomas, melanocytic nevi, warts, cysts, and other adnexal neoplasms.³ In our case, the lesion was abnormally large and was clinically concerning for an unusual sebaceous nevus. Its location on the lower back is not commonly noted and should remind the clinician of the possibility of apocrine differentiation. Clinicians should be aware of the wide phenotypic diversity of eccrine poromas, and therefore they should consider this diagnosis in their differential diagnosis for solitary papules or nodules occurring in any anatomic area.