Patient Presentation
A 47-year-old African-American female presented to our clinic with a 1-month history of a “rash” in her axillae. She denied any change in personal hygiene products around the time the eruption appeared. She was otherwise healthy, had no known history of allergies and was taking no medications. The patient used topical Neosporin Ointment (Polymyxin B-Sulfate-Bacitracin Zinc-Neomycin Sulfate) on both axillae for 2 weeks, which caused the axillary skin changes to become slightly more pronounced. Upon physical examination, there were hyperkeratotic, hyperpigmented plaques measuring approximately 3 cm by 2 cm in her left axilla. The right axilla had similar smaller plaques. A biopsy was performed to confirm the diagnosis. ____________________________
Diagnosis: Axillary Granular Parakeratosis
Axillary granular parakeratosis (AGP), also known as granular parakeratosis and intertriginous granular parakeratosis, is a rare disorder of the keratinization process resulting in dark red pigmented or erythematous keratotic plaques. These plaques develop most commonly in the axillae.1,2,3,4,5,6 Less frequently, AGP has been described in intertriginous areas other than axillae, such as the groin and submammary folds, leading some authors to exclude the word “axillary” from the name. AGP is predominantly seen in women and shows no significant difference in incidence between age of onset and ethnic groups. AGP was relatively recently described in 1991 by Northcutt and colleagues,7 who initially proposed it to be caused by contact with an irritant such as deodorant.
Clinical Features
Clinically, AGP presents as dark red, brownish, or erythematous hyperkeratotic papules or plaques. Commonly occurring in the axillae, it is also seen in other intertriginous areas such as inframammary folds and the groin. A crust may be evident on the affected area, and sparse papules in the surrounding area may be present. Patients may experience pruritus along with a burning sensation — especially if erosion or fissures are present. Patients may also report that heat, humidity and perspiration are aggravating factors. The lesions usually last for at least a month, but they may last longer and may recur after intermittent resolution.8,9,10,11
Pathogenesis
The mechanism of AGP is related to the inhibition of the metabolism of profilaggrin to filaggrin during the process of cornification, resulting in disruption of the keratinization process. The defect leads to a buildup of keratohyalin granules in the stratum corneum, producing a thick, granular appearance. Filaggrin is an adhesion molecule essential to the cornification process. Without it, keratohyaline granules are not degraded and keratin filaments aggregate in corneocytes. Studies show that filaggrin is absent in keratinocytes affected with AGP.12 The original etiologic proposition of AGP pointed to deodorants or other hygiene products as potential culprits. However, many studies have presented evidence opposing this theory.2,4 For example, a substantial number of cases have been reported without an aggravating topical product, unilateral intertriginous involvement, and no improvement upon discontinuation of current topical products.4,6 Therefore, this theory is no longer widely supported as a complete explanation of cause. Several studies continue to correlate AGP with deodorant or other topical irritants in addition to constant warmth and humidity, as is often seen in intertriginous areas of obese patients. The current consensus seems to be that while topical skin care products may aggravate AGP, they are not the cause.6 Infantile AGP presents on the inguinal folds and is thought to be aggravated by an irritant in diapers. Finally, AGP may present in conjunction with obesity and has also recently been linked to dermatophytosis.4,6,7
Histologic Features
The typical histopathology of AGP demonstrates thickened, granular-appearing eosinophilic staining stratum corneum. These findings represent retention of basophilic keratohyalin granules, vascular proliferation and compact parakeratosis. These unique histological features are necessary for a diagnosis. Histological samples may also show an inflammatory infiltrate containing CD4+ T cells in the upper dermis accompanied by moderate capillary dilation and proliferation. Histological examination of the stratum corneum is definitively diagnostic, and any method of biopsy that includes the stratum conrneum can be sufficient for diagnosis. The stratum granulosum is usually of normal thickness and intact, but may show focal vacuolization.6,12 Our patient’s biopsy specimen exhibited mild to moderate acanthosis with mild papillomatosis with confluent parakeratosis and retention of the underlying granular cell layer. These findings were consistent with the diagnosis of granular parakeratosis.
Differential Diagnosis
A number of common diseases may appear to be clinically similar to AGP, giving the unique histological appearance of AGP importance. Several diseases to consider in a differential diagnosis are: seborrheic dermatitis, Hailey-Hailey disease, Darier’s disease, pemphigus vegetans, lichen planus, and acanthosis nigricans.3,4,5,6,7,8 Seborrheic dermatitis is a disorder affecting areas of skin rich in sebaceous glands, such as the scalp, face and axilla, causing erythematous, greasy and scaly patches accompanied by pruritus. The cause is unknown, but it is thought to be an inflammatory response to yeast.13 Hailey-Hailey disease (HH), also known as familial benign pemphigus, is a genodermatosis due to a ATP2C1 genetic defect that has an autosomal dominant inheritance pattern. The average age of onset of HH is 30 to 40 years old. Patients present with blisters, often on an erythematous base, erosions and crusts. Infection and malodor frequently accompany the eruption. The lesions are often pruritic with burning sensations. HH lesions are common in the axillary folds and other intertriginous areas. Histological samples of skin will show prominent acantholysis. HH is a chronic disease with common remittance and relapse, whereas AGP usually heals with treatment and does not typically reoccur. Darier’s disease (DD) is a genetic disorder of the keratinizing process due to a genetic defect of ATP2A2. In the early stages, patients will typically present with small, dark red to brown papules, especially in seborrheic areas. A hallmark of DD seen on a histological sample is dyskeratosis with corps ronds accompanied by acantholysis. Nail and palmar abnormalities are also characteristic of DD.14 Pemphigus vegetans (PV) is a rare variant of the autoimmune disease pemphigus. It is characterized by vegetating plaques in the intertriginous areas, which can be distinguished from AGP by use of direct immunofluorescence showing IgG and C3 deposited on keratinocytes of the dermis. PV also involves a cellular infiltrate in the dermis of neutrophils, eosinophils and lymphocytes. Lichen planus (LP) is an autoimmune disease characterized by cytotoxic CD8+ T-Cells targeting an antigen in the basal epithelium. Patients present with pruritic, exfoliative plaques that are violaceous in color. Plaques range from subacute to chronic and may appear on any cutaneous area.8,9,10 Histological samples show hypergranulosis, hyperkeratosis, acanthosis, and elongation of the rete pegs. This is distinguished from the typical AGP histological sample with a normal stratum granulosum (but with possible vacuolization) and no acanthosis or elongated rete pegs. Other conditions to be considered in the differential diagnosis include acanthosis nigricans, intertrigo, allergic and irritant contact dermatitis, tinea cruris, candidiasis and erythrasma.
Treatment
Currently there is no gold standard therapy for AGP. Some authors have reported successful resolution of AGP lesions with topical corticosteroids, topical vitamin D analogues, and oral and topical retinoids such as isotretinoin, tretinoin and tazarotene. Retinoids function by modulation of cell growth as well as regulate appropriate epidermal maturation and cornification by binding to the retinoic acid receptor and the retinoic receptor, leading to expression of various effectors. The result is that keratinocytes are more easily exfoliated. Ammonium lactate, with its keratolytic properties, is also a viable treatment option for AGP.10 Antibiotics, antifungals, cryotherapy and botulinum toxin injections have also been reported as successful in some cases.10,11 Lesions may clear spontaneously in some cases, but this does not preclude the patient from experiencing relapses, although relapses are rare. Our patient was treated with tazarotene (Tazorac 0.05%) cream once a day, which cleared the plaques in approximately 2 months.
Ms. Southwell is a medical student at the University of North Carolina School of Medicine, Chapel Hill. Dr. Lockshin is in private practice in Silver Spring, MD, and with the Department of Dermatology, Johns Hopkins University, Baltimore, MD. Dr. Blyumin is with the Miller School of Medicine at the University of Miami. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY.
Patient Presentation
A 47-year-old African-American female presented to our clinic with a 1-month history of a “rash” in her axillae. She denied any change in personal hygiene products around the time the eruption appeared. She was otherwise healthy, had no known history of allergies and was taking no medications. The patient used topical Neosporin Ointment (Polymyxin B-Sulfate-Bacitracin Zinc-Neomycin Sulfate) on both axillae for 2 weeks, which caused the axillary skin changes to become slightly more pronounced. Upon physical examination, there were hyperkeratotic, hyperpigmented plaques measuring approximately 3 cm by 2 cm in her left axilla. The right axilla had similar smaller plaques. A biopsy was performed to confirm the diagnosis. ____________________________
Diagnosis: Axillary Granular Parakeratosis
Axillary granular parakeratosis (AGP), also known as granular parakeratosis and intertriginous granular parakeratosis, is a rare disorder of the keratinization process resulting in dark red pigmented or erythematous keratotic plaques. These plaques develop most commonly in the axillae.1,2,3,4,5,6 Less frequently, AGP has been described in intertriginous areas other than axillae, such as the groin and submammary folds, leading some authors to exclude the word “axillary” from the name. AGP is predominantly seen in women and shows no significant difference in incidence between age of onset and ethnic groups. AGP was relatively recently described in 1991 by Northcutt and colleagues,7 who initially proposed it to be caused by contact with an irritant such as deodorant.
Clinical Features
Clinically, AGP presents as dark red, brownish, or erythematous hyperkeratotic papules or plaques. Commonly occurring in the axillae, it is also seen in other intertriginous areas such as inframammary folds and the groin. A crust may be evident on the affected area, and sparse papules in the surrounding area may be present. Patients may experience pruritus along with a burning sensation — especially if erosion or fissures are present. Patients may also report that heat, humidity and perspiration are aggravating factors. The lesions usually last for at least a month, but they may last longer and may recur after intermittent resolution.8,9,10,11
Pathogenesis
The mechanism of AGP is related to the inhibition of the metabolism of profilaggrin to filaggrin during the process of cornification, resulting in disruption of the keratinization process. The defect leads to a buildup of keratohyalin granules in the stratum corneum, producing a thick, granular appearance. Filaggrin is an adhesion molecule essential to the cornification process. Without it, keratohyaline granules are not degraded and keratin filaments aggregate in corneocytes. Studies show that filaggrin is absent in keratinocytes affected with AGP.12 The original etiologic proposition of AGP pointed to deodorants or other hygiene products as potential culprits. However, many studies have presented evidence opposing this theory.2,4 For example, a substantial number of cases have been reported without an aggravating topical product, unilateral intertriginous involvement, and no improvement upon discontinuation of current topical products.4,6 Therefore, this theory is no longer widely supported as a complete explanation of cause. Several studies continue to correlate AGP with deodorant or other topical irritants in addition to constant warmth and humidity, as is often seen in intertriginous areas of obese patients. The current consensus seems to be that while topical skin care products may aggravate AGP, they are not the cause.6 Infantile AGP presents on the inguinal folds and is thought to be aggravated by an irritant in diapers. Finally, AGP may present in conjunction with obesity and has also recently been linked to dermatophytosis.4,6,7
Histologic Features
The typical histopathology of AGP demonstrates thickened, granular-appearing eosinophilic staining stratum corneum. These findings represent retention of basophilic keratohyalin granules, vascular proliferation and compact parakeratosis. These unique histological features are necessary for a diagnosis. Histological samples may also show an inflammatory infiltrate containing CD4+ T cells in the upper dermis accompanied by moderate capillary dilation and proliferation. Histological examination of the stratum corneum is definitively diagnostic, and any method of biopsy that includes the stratum conrneum can be sufficient for diagnosis. The stratum granulosum is usually of normal thickness and intact, but may show focal vacuolization.6,12 Our patient’s biopsy specimen exhibited mild to moderate acanthosis with mild papillomatosis with confluent parakeratosis and retention of the underlying granular cell layer. These findings were consistent with the diagnosis of granular parakeratosis.
Differential Diagnosis
A number of common diseases may appear to be clinically similar to AGP, giving the unique histological appearance of AGP importance. Several diseases to consider in a differential diagnosis are: seborrheic dermatitis, Hailey-Hailey disease, Darier’s disease, pemphigus vegetans, lichen planus, and acanthosis nigricans.3,4,5,6,7,8 Seborrheic dermatitis is a disorder affecting areas of skin rich in sebaceous glands, such as the scalp, face and axilla, causing erythematous, greasy and scaly patches accompanied by pruritus. The cause is unknown, but it is thought to be an inflammatory response to yeast.13 Hailey-Hailey disease (HH), also known as familial benign pemphigus, is a genodermatosis due to a ATP2C1 genetic defect that has an autosomal dominant inheritance pattern. The average age of onset of HH is 30 to 40 years old. Patients present with blisters, often on an erythematous base, erosions and crusts. Infection and malodor frequently accompany the eruption. The lesions are often pruritic with burning sensations. HH lesions are common in the axillary folds and other intertriginous areas. Histological samples of skin will show prominent acantholysis. HH is a chronic disease with common remittance and relapse, whereas AGP usually heals with treatment and does not typically reoccur. Darier’s disease (DD) is a genetic disorder of the keratinizing process due to a genetic defect of ATP2A2. In the early stages, patients will typically present with small, dark red to brown papules, especially in seborrheic areas. A hallmark of DD seen on a histological sample is dyskeratosis with corps ronds accompanied by acantholysis. Nail and palmar abnormalities are also characteristic of DD.14 Pemphigus vegetans (PV) is a rare variant of the autoimmune disease pemphigus. It is characterized by vegetating plaques in the intertriginous areas, which can be distinguished from AGP by use of direct immunofluorescence showing IgG and C3 deposited on keratinocytes of the dermis. PV also involves a cellular infiltrate in the dermis of neutrophils, eosinophils and lymphocytes. Lichen planus (LP) is an autoimmune disease characterized by cytotoxic CD8+ T-Cells targeting an antigen in the basal epithelium. Patients present with pruritic, exfoliative plaques that are violaceous in color. Plaques range from subacute to chronic and may appear on any cutaneous area.8,9,10 Histological samples show hypergranulosis, hyperkeratosis, acanthosis, and elongation of the rete pegs. This is distinguished from the typical AGP histological sample with a normal stratum granulosum (but with possible vacuolization) and no acanthosis or elongated rete pegs. Other conditions to be considered in the differential diagnosis include acanthosis nigricans, intertrigo, allergic and irritant contact dermatitis, tinea cruris, candidiasis and erythrasma.
Treatment
Currently there is no gold standard therapy for AGP. Some authors have reported successful resolution of AGP lesions with topical corticosteroids, topical vitamin D analogues, and oral and topical retinoids such as isotretinoin, tretinoin and tazarotene. Retinoids function by modulation of cell growth as well as regulate appropriate epidermal maturation and cornification by binding to the retinoic acid receptor and the retinoic receptor, leading to expression of various effectors. The result is that keratinocytes are more easily exfoliated. Ammonium lactate, with its keratolytic properties, is also a viable treatment option for AGP.10 Antibiotics, antifungals, cryotherapy and botulinum toxin injections have also been reported as successful in some cases.10,11 Lesions may clear spontaneously in some cases, but this does not preclude the patient from experiencing relapses, although relapses are rare. Our patient was treated with tazarotene (Tazorac 0.05%) cream once a day, which cleared the plaques in approximately 2 months.
Ms. Southwell is a medical student at the University of North Carolina School of Medicine, Chapel Hill. Dr. Lockshin is in private practice in Silver Spring, MD, and with the Department of Dermatology, Johns Hopkins University, Baltimore, MD. Dr. Blyumin is with the Miller School of Medicine at the University of Miami. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY.
Patient Presentation
A 47-year-old African-American female presented to our clinic with a 1-month history of a “rash” in her axillae. She denied any change in personal hygiene products around the time the eruption appeared. She was otherwise healthy, had no known history of allergies and was taking no medications. The patient used topical Neosporin Ointment (Polymyxin B-Sulfate-Bacitracin Zinc-Neomycin Sulfate) on both axillae for 2 weeks, which caused the axillary skin changes to become slightly more pronounced. Upon physical examination, there were hyperkeratotic, hyperpigmented plaques measuring approximately 3 cm by 2 cm in her left axilla. The right axilla had similar smaller plaques. A biopsy was performed to confirm the diagnosis. ____________________________
Diagnosis: Axillary Granular Parakeratosis
Axillary granular parakeratosis (AGP), also known as granular parakeratosis and intertriginous granular parakeratosis, is a rare disorder of the keratinization process resulting in dark red pigmented or erythematous keratotic plaques. These plaques develop most commonly in the axillae.1,2,3,4,5,6 Less frequently, AGP has been described in intertriginous areas other than axillae, such as the groin and submammary folds, leading some authors to exclude the word “axillary” from the name. AGP is predominantly seen in women and shows no significant difference in incidence between age of onset and ethnic groups. AGP was relatively recently described in 1991 by Northcutt and colleagues,7 who initially proposed it to be caused by contact with an irritant such as deodorant.
Clinical Features
Clinically, AGP presents as dark red, brownish, or erythematous hyperkeratotic papules or plaques. Commonly occurring in the axillae, it is also seen in other intertriginous areas such as inframammary folds and the groin. A crust may be evident on the affected area, and sparse papules in the surrounding area may be present. Patients may experience pruritus along with a burning sensation — especially if erosion or fissures are present. Patients may also report that heat, humidity and perspiration are aggravating factors. The lesions usually last for at least a month, but they may last longer and may recur after intermittent resolution.8,9,10,11
Pathogenesis
The mechanism of AGP is related to the inhibition of the metabolism of profilaggrin to filaggrin during the process of cornification, resulting in disruption of the keratinization process. The defect leads to a buildup of keratohyalin granules in the stratum corneum, producing a thick, granular appearance. Filaggrin is an adhesion molecule essential to the cornification process. Without it, keratohyaline granules are not degraded and keratin filaments aggregate in corneocytes. Studies show that filaggrin is absent in keratinocytes affected with AGP.12 The original etiologic proposition of AGP pointed to deodorants or other hygiene products as potential culprits. However, many studies have presented evidence opposing this theory.2,4 For example, a substantial number of cases have been reported without an aggravating topical product, unilateral intertriginous involvement, and no improvement upon discontinuation of current topical products.4,6 Therefore, this theory is no longer widely supported as a complete explanation of cause. Several studies continue to correlate AGP with deodorant or other topical irritants in addition to constant warmth and humidity, as is often seen in intertriginous areas of obese patients. The current consensus seems to be that while topical skin care products may aggravate AGP, they are not the cause.6 Infantile AGP presents on the inguinal folds and is thought to be aggravated by an irritant in diapers. Finally, AGP may present in conjunction with obesity and has also recently been linked to dermatophytosis.4,6,7
Histologic Features
The typical histopathology of AGP demonstrates thickened, granular-appearing eosinophilic staining stratum corneum. These findings represent retention of basophilic keratohyalin granules, vascular proliferation and compact parakeratosis. These unique histological features are necessary for a diagnosis. Histological samples may also show an inflammatory infiltrate containing CD4+ T cells in the upper dermis accompanied by moderate capillary dilation and proliferation. Histological examination of the stratum corneum is definitively diagnostic, and any method of biopsy that includes the stratum conrneum can be sufficient for diagnosis. The stratum granulosum is usually of normal thickness and intact, but may show focal vacuolization.6,12 Our patient’s biopsy specimen exhibited mild to moderate acanthosis with mild papillomatosis with confluent parakeratosis and retention of the underlying granular cell layer. These findings were consistent with the diagnosis of granular parakeratosis.
Differential Diagnosis
A number of common diseases may appear to be clinically similar to AGP, giving the unique histological appearance of AGP importance. Several diseases to consider in a differential diagnosis are: seborrheic dermatitis, Hailey-Hailey disease, Darier’s disease, pemphigus vegetans, lichen planus, and acanthosis nigricans.3,4,5,6,7,8 Seborrheic dermatitis is a disorder affecting areas of skin rich in sebaceous glands, such as the scalp, face and axilla, causing erythematous, greasy and scaly patches accompanied by pruritus. The cause is unknown, but it is thought to be an inflammatory response to yeast.13 Hailey-Hailey disease (HH), also known as familial benign pemphigus, is a genodermatosis due to a ATP2C1 genetic defect that has an autosomal dominant inheritance pattern. The average age of onset of HH is 30 to 40 years old. Patients present with blisters, often on an erythematous base, erosions and crusts. Infection and malodor frequently accompany the eruption. The lesions are often pruritic with burning sensations. HH lesions are common in the axillary folds and other intertriginous areas. Histological samples of skin will show prominent acantholysis. HH is a chronic disease with common remittance and relapse, whereas AGP usually heals with treatment and does not typically reoccur. Darier’s disease (DD) is a genetic disorder of the keratinizing process due to a genetic defect of ATP2A2. In the early stages, patients will typically present with small, dark red to brown papules, especially in seborrheic areas. A hallmark of DD seen on a histological sample is dyskeratosis with corps ronds accompanied by acantholysis. Nail and palmar abnormalities are also characteristic of DD.14 Pemphigus vegetans (PV) is a rare variant of the autoimmune disease pemphigus. It is characterized by vegetating plaques in the intertriginous areas, which can be distinguished from AGP by use of direct immunofluorescence showing IgG and C3 deposited on keratinocytes of the dermis. PV also involves a cellular infiltrate in the dermis of neutrophils, eosinophils and lymphocytes. Lichen planus (LP) is an autoimmune disease characterized by cytotoxic CD8+ T-Cells targeting an antigen in the basal epithelium. Patients present with pruritic, exfoliative plaques that are violaceous in color. Plaques range from subacute to chronic and may appear on any cutaneous area.8,9,10 Histological samples show hypergranulosis, hyperkeratosis, acanthosis, and elongation of the rete pegs. This is distinguished from the typical AGP histological sample with a normal stratum granulosum (but with possible vacuolization) and no acanthosis or elongated rete pegs. Other conditions to be considered in the differential diagnosis include acanthosis nigricans, intertrigo, allergic and irritant contact dermatitis, tinea cruris, candidiasis and erythrasma.
Treatment
Currently there is no gold standard therapy for AGP. Some authors have reported successful resolution of AGP lesions with topical corticosteroids, topical vitamin D analogues, and oral and topical retinoids such as isotretinoin, tretinoin and tazarotene. Retinoids function by modulation of cell growth as well as regulate appropriate epidermal maturation and cornification by binding to the retinoic acid receptor and the retinoic receptor, leading to expression of various effectors. The result is that keratinocytes are more easily exfoliated. Ammonium lactate, with its keratolytic properties, is also a viable treatment option for AGP.10 Antibiotics, antifungals, cryotherapy and botulinum toxin injections have also been reported as successful in some cases.10,11 Lesions may clear spontaneously in some cases, but this does not preclude the patient from experiencing relapses, although relapses are rare. Our patient was treated with tazarotene (Tazorac 0.05%) cream once a day, which cleared the plaques in approximately 2 months.
Ms. Southwell is a medical student at the University of North Carolina School of Medicine, Chapel Hill. Dr. Lockshin is in private practice in Silver Spring, MD, and with the Department of Dermatology, Johns Hopkins University, Baltimore, MD. Dr. Blyumin is with the Miller School of Medicine at the University of Miami. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY.
