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The Diagnosis: Disseminated Coccidioidomycosis

Fungi of the genus Coccidioides cause coccidioidomycosis and live in the soil of endemic areas including the southwestern United States (eg, Arizona, New Mexico, California) and Mexico. Coccidioides is a dimorphic fungus with parasitic and infectious saprophytic phases. Each year there are approximately 150,000 new infections of coccidioidomycosis in the United States, almost exclusively in the southwest.¹ Coccidioidomycosis typically is an asymptomatic or mild infection in an immunocompetent patient. Although the lungs are nearly always the primary sites of infection, common sites of dissemination include the skin, meninges, bones, and joints. The skin is the most common site of disseminated, or secondary, coccidioidomycosis.² Less commonly and usually caused by traumatic implantation, the skin is the site of primary infection.

Disseminated coccidioidomycosis occurs in approximately 1 in 200 infected individuals.^2,3 Certain populations of patients are more likely to be affected by disseminated coccidioidomycosis, including specific ethnic groups such as black individuals, Filipinos, and Mexicans^4,5; pregnant women⁶; and immunosuppressed patients such as those with human immunodeficiency virus, hematogenous malignancy, or organ transplantation.^7-9 When skin lesions are present, they usually develop after the initial lung manifestation. The location of the lesion in cutaneous disseminated disease can be highly variable, but the face and head are the most common locations (30%).¹⁰

Cutaneous manifestations of coccidioidomycosis may be classified as being caused by the presence of the organism in the skin (organism specific) or a reactive process. Organism-specific cutaneous lesions are commonly due to systemic disease with secondary skin involvement, but they also may be due to a primary infection. These organism-specific lesions can present as papules, nodules, macules, verrucous plaques, abscesses, or pustules. Reactive cutaneous manifestations are only associated with disseminated disease; do not contain any organisms; and include manifestations such as erythema nodosum, acute exanthem, erythema multiforme, and possibly Sweet syndrome.¹¹

The clinical differential diagnosis of cutaneous coccidioidomycosis includes other

Coccidioidal spherules in the dermis (Periodic acid–Schiff, original magnification ×600).

mycoses such as histoplasmosis and blastomycosis, as well as tuberculosis, sarcoidosis, basal cell and squamous cell carcinoma, and verruca vulgaris. The diagnosis of cutaneous coccidioidomycosis can be made with skin biopsy, culture, and serologic tests. The characteristic spherules can be visualized on routine hematoxylin and eosin stain or more readily with fungal stains (Figure). Spherules are thick walled and distinguishable from other fungi because of the characteristic endospores inside as well as their larger size. Organisms also may be detected via culture within 2 to 5 days.

Distinguishing primary cutaneous from disseminated skin lesions can be challenging but can have notable treatment implications. Although histology typically cannot distinguish primary from disseminated cutaneous infections, clinical history and serologic studies have been found to be useful. In disseminated disease, IgG antibodies are elevated, while in primary cutaneous disease, IgM antibodies are elevated but typically not IgG.¹² Therefore, tube precipitin and latex particle agglutination tests that detect IgM antibodies should be positive in primary infections.¹³ Primary lesions can spontaneously resolve within months to years and may not require treatment if symptomatic, while secondary lesions must be therapeutically addressed.¹² Despite the lack of treatment needed, primary cutaneous infections often are treated with azoles.¹⁴ In contrast, disseminated cutaneous infection requires systemic therapy. Treatment of disseminated infection with cutaneous coccidioidomycosis typically includes amphotericin B until a clinical response is achieved and antibody titers decline. Amphotericin B can then be replaced with an oral azole such as itraconozole or fluconazole.¹⁵

The patient discussed in this case demonstrates the typical clinical presentation of disseminated coccidioidomycosis with classical and diagnostic pathology. This case also highlights the importance of a detailed travel history; in the era of globalization, patients often present with diseases in nonendemic areas. Clinicians must consider the diagnosis of coccidioidomycosis, even in immunocompetent patients in nonendemic areas when their history and presentation are appropriate. The diagnosis should be confirmed with biopsy, culture, and/or serology.

The Diagnosis: Disseminated Coccidioidomycosis

Fungi of the genus Coccidioides cause coccidioidomycosis and live in the soil of endemic areas including the southwestern United States (eg, Arizona, New Mexico, California) and Mexico. Coccidioides is a dimorphic fungus with parasitic and infectious saprophytic phases. Each year there are approximately 150,000 new infections of coccidioidomycosis in the United States, almost exclusively in the southwest.¹ Coccidioidomycosis typically is an asymptomatic or mild infection in an immunocompetent patient. Although the lungs are nearly always the primary sites of infection, common sites of dissemination include the skin, meninges, bones, and joints. The skin is the most common site of disseminated, or secondary, coccidioidomycosis.² Less commonly and usually caused by traumatic implantation, the skin is the site of primary infection.

Disseminated coccidioidomycosis occurs in approximately 1 in 200 infected individuals.^2,3 Certain populations of patients are more likely to be affected by disseminated coccidioidomycosis, including specific ethnic groups such as black individuals, Filipinos, and Mexicans^4,5; pregnant women⁶; and immunosuppressed patients such as those with human immunodeficiency virus, hematogenous malignancy, or organ transplantation.^7-9 When skin lesions are present, they usually develop after the initial lung manifestation. The location of the lesion in cutaneous disseminated disease can be highly variable, but the face and head are the most common locations (30%).¹⁰

Cutaneous manifestations of coccidioidomycosis may be classified as being caused by the presence of the organism in the skin (organism specific) or a reactive process. Organism-specific cutaneous lesions are commonly due to systemic disease with secondary skin involvement, but they also may be due to a primary infection. These organism-specific lesions can present as papules, nodules, macules, verrucous plaques, abscesses, or pustules. Reactive cutaneous manifestations are only associated with disseminated disease; do not contain any organisms; and include manifestations such as erythema nodosum, acute exanthem, erythema multiforme, and possibly Sweet syndrome.¹¹

The clinical differential diagnosis of cutaneous coccidioidomycosis includes other

Coccidioidal spherules in the dermis (Periodic acid–Schiff, original magnification ×600).

mycoses such as histoplasmosis and blastomycosis, as well as tuberculosis, sarcoidosis, basal cell and squamous cell carcinoma, and verruca vulgaris. The diagnosis of cutaneous coccidioidomycosis can be made with skin biopsy, culture, and serologic tests. The characteristic spherules can be visualized on routine hematoxylin and eosin stain or more readily with fungal stains (Figure). Spherules are thick walled and distinguishable from other fungi because of the characteristic endospores inside as well as their larger size. Organisms also may be detected via culture within 2 to 5 days.

Distinguishing primary cutaneous from disseminated skin lesions can be challenging but can have notable treatment implications. Although histology typically cannot distinguish primary from disseminated cutaneous infections, clinical history and serologic studies have been found to be useful. In disseminated disease, IgG antibodies are elevated, while in primary cutaneous disease, IgM antibodies are elevated but typically not IgG.¹² Therefore, tube precipitin and latex particle agglutination tests that detect IgM antibodies should be positive in primary infections.¹³ Primary lesions can spontaneously resolve within months to years and may not require treatment if symptomatic, while secondary lesions must be therapeutically addressed.¹² Despite the lack of treatment needed, primary cutaneous infections often are treated with azoles.¹⁴ In contrast, disseminated cutaneous infection requires systemic therapy. Treatment of disseminated infection with cutaneous coccidioidomycosis typically includes amphotericin B until a clinical response is achieved and antibody titers decline. Amphotericin B can then be replaced with an oral azole such as itraconozole or fluconazole.¹⁵

The patient discussed in this case demonstrates the typical clinical presentation of disseminated coccidioidomycosis with classical and diagnostic pathology. This case also highlights the importance of a detailed travel history; in the era of globalization, patients often present with diseases in nonendemic areas. Clinicians must consider the diagnosis of coccidioidomycosis, even in immunocompetent patients in nonendemic areas when their history and presentation are appropriate. The diagnosis should be confirmed with biopsy, culture, and/or serology.

The Diagnosis: Disseminated Coccidioidomycosis

Fungi of the genus Coccidioides cause coccidioidomycosis and live in the soil of endemic areas including the southwestern United States (eg, Arizona, New Mexico, California) and Mexico. Coccidioides is a dimorphic fungus with parasitic and infectious saprophytic phases. Each year there are approximately 150,000 new infections of coccidioidomycosis in the United States, almost exclusively in the southwest.¹ Coccidioidomycosis typically is an asymptomatic or mild infection in an immunocompetent patient. Although the lungs are nearly always the primary sites of infection, common sites of dissemination include the skin, meninges, bones, and joints. The skin is the most common site of disseminated, or secondary, coccidioidomycosis.² Less commonly and usually caused by traumatic implantation, the skin is the site of primary infection.

Disseminated coccidioidomycosis occurs in approximately 1 in 200 infected individuals.^2,3 Certain populations of patients are more likely to be affected by disseminated coccidioidomycosis, including specific ethnic groups such as black individuals, Filipinos, and Mexicans^4,5; pregnant women⁶; and immunosuppressed patients such as those with human immunodeficiency virus, hematogenous malignancy, or organ transplantation.^7-9 When skin lesions are present, they usually develop after the initial lung manifestation. The location of the lesion in cutaneous disseminated disease can be highly variable, but the face and head are the most common locations (30%).¹⁰

Cutaneous manifestations of coccidioidomycosis may be classified as being caused by the presence of the organism in the skin (organism specific) or a reactive process. Organism-specific cutaneous lesions are commonly due to systemic disease with secondary skin involvement, but they also may be due to a primary infection. These organism-specific lesions can present as papules, nodules, macules, verrucous plaques, abscesses, or pustules. Reactive cutaneous manifestations are only associated with disseminated disease; do not contain any organisms; and include manifestations such as erythema nodosum, acute exanthem, erythema multiforme, and possibly Sweet syndrome.¹¹

The clinical differential diagnosis of cutaneous coccidioidomycosis includes other

Coccidioidal spherules in the dermis (Periodic acid–Schiff, original magnification ×600).

mycoses such as histoplasmosis and blastomycosis, as well as tuberculosis, sarcoidosis, basal cell and squamous cell carcinoma, and verruca vulgaris. The diagnosis of cutaneous coccidioidomycosis can be made with skin biopsy, culture, and serologic tests. The characteristic spherules can be visualized on routine hematoxylin and eosin stain or more readily with fungal stains (Figure). Spherules are thick walled and distinguishable from other fungi because of the characteristic endospores inside as well as their larger size. Organisms also may be detected via culture within 2 to 5 days.

Distinguishing primary cutaneous from disseminated skin lesions can be challenging but can have notable treatment implications. Although histology typically cannot distinguish primary from disseminated cutaneous infections, clinical history and serologic studies have been found to be useful. In disseminated disease, IgG antibodies are elevated, while in primary cutaneous disease, IgM antibodies are elevated but typically not IgG.¹² Therefore, tube precipitin and latex particle agglutination tests that detect IgM antibodies should be positive in primary infections.¹³ Primary lesions can spontaneously resolve within months to years and may not require treatment if symptomatic, while secondary lesions must be therapeutically addressed.¹² Despite the lack of treatment needed, primary cutaneous infections often are treated with azoles.¹⁴ In contrast, disseminated cutaneous infection requires systemic therapy. Treatment of disseminated infection with cutaneous coccidioidomycosis typically includes amphotericin B until a clinical response is achieved and antibody titers decline. Amphotericin B can then be replaced with an oral azole such as itraconozole or fluconazole.¹⁵

The patient discussed in this case demonstrates the typical clinical presentation of disseminated coccidioidomycosis with classical and diagnostic pathology. This case also highlights the importance of a detailed travel history; in the era of globalization, patients often present with diseases in nonendemic areas. Clinicians must consider the diagnosis of coccidioidomycosis, even in immunocompetent patients in nonendemic areas when their history and presentation are appropriate. The diagnosis should be confirmed with biopsy, culture, and/or serology.

The Diagnosis: Prayer Callus

After our patient demonstrated his routine position for prayer (Figure), the

The position of the patient’s left foot while praying.

diagnosis of prayer callus was confirmed. We suggested he use a foam pad under his foot during prayer. The patient did not return for follow-up.

Prayer calluses have been documented in the literature as prayer nodules^1-3 or marks.⁴ Callus is a preferred term, as it implies the act of repeated pressure or friction to an area of the skin. It is more descriptive than marks and avoids the inclusion of nodules caused by different prayer or religious activities such as ritual scarring.⁵

Abanmi et al⁴ studied a large group (N=349) of Muslim patients with regular praying habits and found a high prevalence of what they referred to as prayer marks, defined by lichenification and/or hyperpigmentation, on the knees, forehead, ankles, and dorsal aspects of the feet. They studied the histopathology of 33 marks. No statistical analysis was performed. They reported common histologic findings of compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. In contrast to lichen simplex chronicus, the authors found that the dermal fibrosis did not exhibit collagen bundles perpendicular to the epidermis.⁴

This study found that a higher prevalence of lichenification was observed on the left foot (males, 57%; females, 39%) than the right foot (males, 14%; females, 19%), which was attributed to a more typical prayer position that placed pressure on the left foot.⁴ Our patient only had calluses on his left foot, which was consistent with the prayer position.

Treatment options for prayer calluses include debridement, either mechanical or with topical keratolytic preparations. There is a high likelihood of recurrence if prayer practices are not changed. Optimally, more definitive treatment, which can be combined with initial debridement, would be position adjustment to lessen pressure or friction to the area or protection over the area with a cushion, as we attempted with our patient in the form of a foam pad.

The Diagnosis: Prayer Callus

After our patient demonstrated his routine position for prayer (Figure), the

The position of the patient’s left foot while praying.

diagnosis of prayer callus was confirmed. We suggested he use a foam pad under his foot during prayer. The patient did not return for follow-up.

Prayer calluses have been documented in the literature as prayer nodules^1-3 or marks.⁴ Callus is a preferred term, as it implies the act of repeated pressure or friction to an area of the skin. It is more descriptive than marks and avoids the inclusion of nodules caused by different prayer or religious activities such as ritual scarring.⁵

Abanmi et al⁴ studied a large group (N=349) of Muslim patients with regular praying habits and found a high prevalence of what they referred to as prayer marks, defined by lichenification and/or hyperpigmentation, on the knees, forehead, ankles, and dorsal aspects of the feet. They studied the histopathology of 33 marks. No statistical analysis was performed. They reported common histologic findings of compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. In contrast to lichen simplex chronicus, the authors found that the dermal fibrosis did not exhibit collagen bundles perpendicular to the epidermis.⁴

This study found that a higher prevalence of lichenification was observed on the left foot (males, 57%; females, 39%) than the right foot (males, 14%; females, 19%), which was attributed to a more typical prayer position that placed pressure on the left foot.⁴ Our patient only had calluses on his left foot, which was consistent with the prayer position.

Treatment options for prayer calluses include debridement, either mechanical or with topical keratolytic preparations. There is a high likelihood of recurrence if prayer practices are not changed. Optimally, more definitive treatment, which can be combined with initial debridement, would be position adjustment to lessen pressure or friction to the area or protection over the area with a cushion, as we attempted with our patient in the form of a foam pad.

The Diagnosis: Prayer Callus

After our patient demonstrated his routine position for prayer (Figure), the

The position of the patient’s left foot while praying.

diagnosis of prayer callus was confirmed. We suggested he use a foam pad under his foot during prayer. The patient did not return for follow-up.

Prayer calluses have been documented in the literature as prayer nodules^1-3 or marks.⁴ Callus is a preferred term, as it implies the act of repeated pressure or friction to an area of the skin. It is more descriptive than marks and avoids the inclusion of nodules caused by different prayer or religious activities such as ritual scarring.⁵

Abanmi et al⁴ studied a large group (N=349) of Muslim patients with regular praying habits and found a high prevalence of what they referred to as prayer marks, defined by lichenification and/or hyperpigmentation, on the knees, forehead, ankles, and dorsal aspects of the feet. They studied the histopathology of 33 marks. No statistical analysis was performed. They reported common histologic findings of compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. In contrast to lichen simplex chronicus, the authors found that the dermal fibrosis did not exhibit collagen bundles perpendicular to the epidermis.⁴

This study found that a higher prevalence of lichenification was observed on the left foot (males, 57%; females, 39%) than the right foot (males, 14%; females, 19%), which was attributed to a more typical prayer position that placed pressure on the left foot.⁴ Our patient only had calluses on his left foot, which was consistent with the prayer position.

Treatment options for prayer calluses include debridement, either mechanical or with topical keratolytic preparations. There is a high likelihood of recurrence if prayer practices are not changed. Optimally, more definitive treatment, which can be combined with initial debridement, would be position adjustment to lessen pressure or friction to the area or protection over the area with a cushion, as we attempted with our patient in the form of a foam pad.

The Diagnosis: Atrophic Lupus Erythematosus

Cutaneous lupus erythematosus is divided into acute, subacute, and chronic cutaneous lupus erythematosus (CCLE). There are more than 20 subtypes of CCLE mentioned in the literature including atrophic lupus erythematosus (ALE).¹ The most typical presentation is CCLE with discoid lesions. Most commonly, discoid CCLE is an entirely cutaneous process without systemic involvement.Discoid lesions appear as scaly red macules or papules primarily on the face and scalp.² They may evolve into hyperkeratotic plaques with irregular hyperpigmented borders and develop a central hypopigmented depression with atrophy and scarring.^2,3 Discoid CCLE has a female predominance and commonly occurs between 20 and 30 years of age. Triggers of discoid lesions include UV exposure, trauma, and infection.² 

Our case of multiple atrophic plaques of the face, scalp, trunk, and upper extremities demonstrated a diagnostic challenge. Our patient presented with atrophic facial plaques, which are not typical of discoid lesions of CCLE. Our patient’s findings appeared clinically similar to acne scarring or atrophoderma. Histology showed common features of CCLE, including basal liquefactive degeneration, thickening of the basement membrane zone, increased melanin, and a lymphocytic inflammatory infiltrate (Figure).^2,3 There was no evidence of hyperkeratosis, which often is seen in discoid lesions of CCLE.

Clinicopathologically, our case was consistent with ALE. A review of the literature revealed similar cases documented by Christianson and Mitchell⁴ in 1969; they described annular atrophic plaques of the skin of unknown diagnostic classification. Chorzelski et al⁵ reiterated the difficulty of defining diagnostically similar atrophic plaques of the face showing histopathologic features consistent with lupus and suggested these cases may represent an uncharacteristic presentation of discoid lupus erythematosus. Our patient demonstrated this rare subtype of discoid lupus erythematosus, known as ALE. There are few reports in the literature of ALE; thus we have managed our patient similar to other CCLE patients. Management of CCLE patients includes strict sun protection. Treatment options include corticosteroids, calcineurin inhibitors, antimalarial agents, and thalidomide.² Our patient started using tacrolimus ointment 0.1% daily and hydroxychloroquine 200 mg twice daily. She also was practicing strict photoprotection. The patient was lost to follow-up. Topical steroids are not an option in ALE. It is important for dermatologists to recognize this rare variant of CCLE to prevent disfigurement.

The Diagnosis: Atrophic Lupus Erythematosus

Cutaneous lupus erythematosus is divided into acute, subacute, and chronic cutaneous lupus erythematosus (CCLE). There are more than 20 subtypes of CCLE mentioned in the literature including atrophic lupus erythematosus (ALE).¹ The most typical presentation is CCLE with discoid lesions. Most commonly, discoid CCLE is an entirely cutaneous process without systemic involvement.Discoid lesions appear as scaly red macules or papules primarily on the face and scalp.² They may evolve into hyperkeratotic plaques with irregular hyperpigmented borders and develop a central hypopigmented depression with atrophy and scarring.^2,3 Discoid CCLE has a female predominance and commonly occurs between 20 and 30 years of age. Triggers of discoid lesions include UV exposure, trauma, and infection.² 

Our case of multiple atrophic plaques of the face, scalp, trunk, and upper extremities demonstrated a diagnostic challenge. Our patient presented with atrophic facial plaques, which are not typical of discoid lesions of CCLE. Our patient’s findings appeared clinically similar to acne scarring or atrophoderma. Histology showed common features of CCLE, including basal liquefactive degeneration, thickening of the basement membrane zone, increased melanin, and a lymphocytic inflammatory infiltrate (Figure).^2,3 There was no evidence of hyperkeratosis, which often is seen in discoid lesions of CCLE.

Clinicopathologically, our case was consistent with ALE. A review of the literature revealed similar cases documented by Christianson and Mitchell⁴ in 1969; they described annular atrophic plaques of the skin of unknown diagnostic classification. Chorzelski et al⁵ reiterated the difficulty of defining diagnostically similar atrophic plaques of the face showing histopathologic features consistent with lupus and suggested these cases may represent an uncharacteristic presentation of discoid lupus erythematosus. Our patient demonstrated this rare subtype of discoid lupus erythematosus, known as ALE. There are few reports in the literature of ALE; thus we have managed our patient similar to other CCLE patients. Management of CCLE patients includes strict sun protection. Treatment options include corticosteroids, calcineurin inhibitors, antimalarial agents, and thalidomide.² Our patient started using tacrolimus ointment 0.1% daily and hydroxychloroquine 200 mg twice daily. She also was practicing strict photoprotection. The patient was lost to follow-up. Topical steroids are not an option in ALE. It is important for dermatologists to recognize this rare variant of CCLE to prevent disfigurement.

The Diagnosis: Atrophic Lupus Erythematosus

Cutaneous lupus erythematosus is divided into acute, subacute, and chronic cutaneous lupus erythematosus (CCLE). There are more than 20 subtypes of CCLE mentioned in the literature including atrophic lupus erythematosus (ALE).¹ The most typical presentation is CCLE with discoid lesions. Most commonly, discoid CCLE is an entirely cutaneous process without systemic involvement.Discoid lesions appear as scaly red macules or papules primarily on the face and scalp.² They may evolve into hyperkeratotic plaques with irregular hyperpigmented borders and develop a central hypopigmented depression with atrophy and scarring.^2,3 Discoid CCLE has a female predominance and commonly occurs between 20 and 30 years of age. Triggers of discoid lesions include UV exposure, trauma, and infection.² 

Our case of multiple atrophic plaques of the face, scalp, trunk, and upper extremities demonstrated a diagnostic challenge. Our patient presented with atrophic facial plaques, which are not typical of discoid lesions of CCLE. Our patient’s findings appeared clinically similar to acne scarring or atrophoderma. Histology showed common features of CCLE, including basal liquefactive degeneration, thickening of the basement membrane zone, increased melanin, and a lymphocytic inflammatory infiltrate (Figure).^2,3 There was no evidence of hyperkeratosis, which often is seen in discoid lesions of CCLE.

Clinicopathologically, our case was consistent with ALE. A review of the literature revealed similar cases documented by Christianson and Mitchell⁴ in 1969; they described annular atrophic plaques of the skin of unknown diagnostic classification. Chorzelski et al⁵ reiterated the difficulty of defining diagnostically similar atrophic plaques of the face showing histopathologic features consistent with lupus and suggested these cases may represent an uncharacteristic presentation of discoid lupus erythematosus. Our patient demonstrated this rare subtype of discoid lupus erythematosus, known as ALE. There are few reports in the literature of ALE; thus we have managed our patient similar to other CCLE patients. Management of CCLE patients includes strict sun protection. Treatment options include corticosteroids, calcineurin inhibitors, antimalarial agents, and thalidomide.² Our patient started using tacrolimus ointment 0.1% daily and hydroxychloroquine 200 mg twice daily. She also was practicing strict photoprotection. The patient was lost to follow-up. Topical steroids are not an option in ALE. It is important for dermatologists to recognize this rare variant of CCLE to prevent disfigurement.

The Diagnosis: Eosinophilic Fasciitis (Shulman Syndrome)

In 1984, Shulman¹ reported 2 cases of diffuse fasciitis with hypergammaglobulinemia and eosinophilia, which was later termed eosinophilic fasciitis (EF) by Rodnan et al.² Eosinophilic fasciitis also is commonly known as diffuse fasciitis with eosinophilia³ or Shulman syndrome.^3,4 It is an inflammatory condition of unknown etiology and pathogenesis, though an underlying autoimmune process has been proposed.^3,5 The disorder is characterized by inflammation and subsequent fibrosis of deep fascia² with variable involvement of the underlying muscle. It often is referred to as a sclerodermalike condition^2,5-8 and is considered to be one of a group of fibrosing connective tissue disorders that may be confused with systemic sclerosis.^3,4,6,9 Although the cause of EF is unknown, more than 50% of cases are associated with vigorous exercise or trauma.³ Other reported triggers and associations include Borrelia burgdorferi infection,^5,6,10 arthropod bites,^5,10 lymphoproliferative and hematologic disorders,^5,6,10 inflammatory arthritis,⁶ morphea,³ thyroid dysfunction,^5,6,10 statins,^5,10 and phenytoin.^5,10

There have been more than 250 cases of EF reported in the literature.³ Some authors report more frequent occurrence in males,^3,4 while others report equal occurrence of disease in both males and females.^5,10 Eosinophilic fasciitis has the highest incidence during the second to sixth decades of life,^3,10 though childhood cases have been reported.^3,11 White individuals appear to be affected most often, but sporadic cases in other ethnic groups also have been reported.³

The clinical presentation of EF frequently is characterized by the rapid onset of erythema, pain, and nonpitting edema of the involved areas.^5,7,10,11 Fatigue and itching also are reported symptoms.¹² A cobblestone texture of the skin may be noted, commonly referred to as the peau d’orange effect.^6,10 Woody induration subsequently develops, which may lead to contracture or limited range of motion.^5,7,11-13 The distal extremities, particularly the forearms and calves, are the most common areas affected by EF.³ There usually is symmetric involvement; however, unilateral cases of EF also have been reported.^3,6,10 Linear indentations may form along the vasculature of the involved areas when the extremities are lifted or extended. These indentations serve to demarcate the underlying muscle groups, forming the groove sign or venous furrowing.^3,5,14 The epidermis is not characteristically involved in EF and wrinkling of the skin can be elicited by pinching,³ which may be helpful in clinically distinguishing EF from scleroderma. Sparing of the digits is another characteristic feature of adult-onset EF.^3,10 However, involvement of the digits resulting in painless contracture has been reported in multiple childhood cases and may represent a phenotype specific to children.¹¹ Involvement of the trunk is less frequently observed but may serve as a poor prognostic indicator; indeed, patients demonstrating young age of onset, morphealike skin sclerosis, and trunk involvement are more likely to develop refractory disease.¹⁵

Eosinophilic fasciitis is characterized by various laboratory abnormalities. Peripheral eosinophilia, hypergammaglobulinemia, elevated sedimentation rate,^{3,6,9,10,13,15} and elevated C-reactive protein^3,6 are commonly reported; however, antinuclear antibody, rheumatoid factor, or antibodies associated with systemic sclerosis are not frequently found.^3,6 There are no laboratory abnormalities required to render a diagnosis of EF, and absence of peripheral eosinophilia has been noted in up to 20% of cases.^3,4 An elevation of creatine kinase or aldolase levels may be present if muscle is involved.^3,6 In general, abnormal laboratory findings have not been found to correlate with disease activity^13,15 and do not appear to have prognostic significance.¹⁵

Biopsy of involved tissue characteristically reveals fascial thickening and fibrosis.^10,13,15 A lymphoplasmacytic infiltrate normally is found in the subcutaneous tissues and fascia and may extend to involve the deeper dermis¹⁵ but usually spares the epidermis.³ It is important to note that increased numbers of eosinophils are not always found in the affected fascia, especially in the later stages of the disease and after steroid treatment.^3,15 Muscle involvement is variable. When muscle is involved, histologic features range from mild inflammation with no evidence of necrosis³ to substantial fibrinoid necrosis.¹³

Magnetic resonance imaging has become a valuable tool in the diagnosis and treatment of EF. Magnetic resonance imaging findings in EF patients typically reveal fascial thickening on T1-weighted images, enhancement after the use of contrast, and hyperintensity on T2-weighted images.⁷ Magnetic resonance imaging has proven useful in supporting clinical diagnosis, monitoring disease activity, identifying optimal biopsy location, and determining response to treatment.^3,7,8,11,13 Magnetic resonance imaging also has been proven to be particularly useful with atypical clinical presentations.⁸ Although deep tissue biopsy remains the gold standard for diagnosis,¹³ magnetic resonance imaging may provide equal or superior diagnostic information.

In general, the prognosis is very good, and the majority of patients will achieve complete remission and cure.³ Up to one-third of patients with EF may experience spontaneous remission without any treatment intervention.¹⁰ The condition generally is highly responsive to oral corticosteroids,^6,10,15 and it has been reported that up to 70% of patients will respond to corticosteroid treatment.³ Most patients respond to a daily dose of prednisone (0.5–1.5 mg/kg), which is continued until clinical response is observed and then followed by a slow steroid taper over a period of several months.³ Patients with persistent fibrosis often require adjunctive therapy in addition to corticosteroids. A variety of adjunctive therapies have been reported to be effective, including hydroxychloroquine sulfate,^{5,10,13,15,16} azathioprine,^15,16 ibuprofen,^10,15 D-penicillamine,^5,15 cyclophosphomide,¹⁵ methotrexate,^6,13,15 cyclosporine,^13,15 psoralen plus UVA,^5,6,15 extracorporeal photochemotherapy,^5,6,10,16 colchicine,⁵ cimetidine,^5,6,10,16 infliximab,^5,6 griseofulvin,¹⁶ ketotifen,¹⁶ sulfasalazine,¹³ and dapsone.¹⁶ Physical therapy has been reported to be useful in preventing permanent joint contractures.^3,5,10,13,16 If treatment fails, the possibility of underlying malignancy must be considered³; however, long courses of treatment are not uncommon. Some patients may need 12 to 18 months of treatment for full response, and even refractory cases are likely to eventually achieve full remission.³

The Diagnosis: Eosinophilic Fasciitis (Shulman Syndrome)

In 1984, Shulman¹ reported 2 cases of diffuse fasciitis with hypergammaglobulinemia and eosinophilia, which was later termed eosinophilic fasciitis (EF) by Rodnan et al.² Eosinophilic fasciitis also is commonly known as diffuse fasciitis with eosinophilia³ or Shulman syndrome.^3,4 It is an inflammatory condition of unknown etiology and pathogenesis, though an underlying autoimmune process has been proposed.^3,5 The disorder is characterized by inflammation and subsequent fibrosis of deep fascia² with variable involvement of the underlying muscle. It often is referred to as a sclerodermalike condition^2,5-8 and is considered to be one of a group of fibrosing connective tissue disorders that may be confused with systemic sclerosis.^3,4,6,9 Although the cause of EF is unknown, more than 50% of cases are associated with vigorous exercise or trauma.³ Other reported triggers and associations include Borrelia burgdorferi infection,^5,6,10 arthropod bites,^5,10 lymphoproliferative and hematologic disorders,^5,6,10 inflammatory arthritis,⁶ morphea,³ thyroid dysfunction,^5,6,10 statins,^5,10 and phenytoin.^5,10

There have been more than 250 cases of EF reported in the literature.³ Some authors report more frequent occurrence in males,^3,4 while others report equal occurrence of disease in both males and females.^5,10 Eosinophilic fasciitis has the highest incidence during the second to sixth decades of life,^3,10 though childhood cases have been reported.^3,11 White individuals appear to be affected most often, but sporadic cases in other ethnic groups also have been reported.³

The clinical presentation of EF frequently is characterized by the rapid onset of erythema, pain, and nonpitting edema of the involved areas.^5,7,10,11 Fatigue and itching also are reported symptoms.¹² A cobblestone texture of the skin may be noted, commonly referred to as the peau d’orange effect.^6,10 Woody induration subsequently develops, which may lead to contracture or limited range of motion.^5,7,11-13 The distal extremities, particularly the forearms and calves, are the most common areas affected by EF.³ There usually is symmetric involvement; however, unilateral cases of EF also have been reported.^3,6,10 Linear indentations may form along the vasculature of the involved areas when the extremities are lifted or extended. These indentations serve to demarcate the underlying muscle groups, forming the groove sign or venous furrowing.^3,5,14 The epidermis is not characteristically involved in EF and wrinkling of the skin can be elicited by pinching,³ which may be helpful in clinically distinguishing EF from scleroderma. Sparing of the digits is another characteristic feature of adult-onset EF.^3,10 However, involvement of the digits resulting in painless contracture has been reported in multiple childhood cases and may represent a phenotype specific to children.¹¹ Involvement of the trunk is less frequently observed but may serve as a poor prognostic indicator; indeed, patients demonstrating young age of onset, morphealike skin sclerosis, and trunk involvement are more likely to develop refractory disease.¹⁵

Eosinophilic fasciitis is characterized by various laboratory abnormalities. Peripheral eosinophilia, hypergammaglobulinemia, elevated sedimentation rate,^{3,6,9,10,13,15} and elevated C-reactive protein^3,6 are commonly reported; however, antinuclear antibody, rheumatoid factor, or antibodies associated with systemic sclerosis are not frequently found.^3,6 There are no laboratory abnormalities required to render a diagnosis of EF, and absence of peripheral eosinophilia has been noted in up to 20% of cases.^3,4 An elevation of creatine kinase or aldolase levels may be present if muscle is involved.^3,6 In general, abnormal laboratory findings have not been found to correlate with disease activity^13,15 and do not appear to have prognostic significance.¹⁵

Biopsy of involved tissue characteristically reveals fascial thickening and fibrosis.^10,13,15 A lymphoplasmacytic infiltrate normally is found in the subcutaneous tissues and fascia and may extend to involve the deeper dermis¹⁵ but usually spares the epidermis.³ It is important to note that increased numbers of eosinophils are not always found in the affected fascia, especially in the later stages of the disease and after steroid treatment.^3,15 Muscle involvement is variable. When muscle is involved, histologic features range from mild inflammation with no evidence of necrosis³ to substantial fibrinoid necrosis.¹³

Magnetic resonance imaging has become a valuable tool in the diagnosis and treatment of EF. Magnetic resonance imaging findings in EF patients typically reveal fascial thickening on T1-weighted images, enhancement after the use of contrast, and hyperintensity on T2-weighted images.⁷ Magnetic resonance imaging has proven useful in supporting clinical diagnosis, monitoring disease activity, identifying optimal biopsy location, and determining response to treatment.^3,7,8,11,13 Magnetic resonance imaging also has been proven to be particularly useful with atypical clinical presentations.⁸ Although deep tissue biopsy remains the gold standard for diagnosis,¹³ magnetic resonance imaging may provide equal or superior diagnostic information.

In general, the prognosis is very good, and the majority of patients will achieve complete remission and cure.³ Up to one-third of patients with EF may experience spontaneous remission without any treatment intervention.¹⁰ The condition generally is highly responsive to oral corticosteroids,^6,10,15 and it has been reported that up to 70% of patients will respond to corticosteroid treatment.³ Most patients respond to a daily dose of prednisone (0.5–1.5 mg/kg), which is continued until clinical response is observed and then followed by a slow steroid taper over a period of several months.³ Patients with persistent fibrosis often require adjunctive therapy in addition to corticosteroids. A variety of adjunctive therapies have been reported to be effective, including hydroxychloroquine sulfate,^{5,10,13,15,16} azathioprine,^15,16 ibuprofen,^10,15 D-penicillamine,^5,15 cyclophosphomide,¹⁵ methotrexate,^6,13,15 cyclosporine,^13,15 psoralen plus UVA,^5,6,15 extracorporeal photochemotherapy,^5,6,10,16 colchicine,⁵ cimetidine,^5,6,10,16 infliximab,^5,6 griseofulvin,¹⁶ ketotifen,¹⁶ sulfasalazine,¹³ and dapsone.¹⁶ Physical therapy has been reported to be useful in preventing permanent joint contractures.^3,5,10,13,16 If treatment fails, the possibility of underlying malignancy must be considered³; however, long courses of treatment are not uncommon. Some patients may need 12 to 18 months of treatment for full response, and even refractory cases are likely to eventually achieve full remission.³

The Diagnosis: Eosinophilic Fasciitis (Shulman Syndrome)

In 1984, Shulman¹ reported 2 cases of diffuse fasciitis with hypergammaglobulinemia and eosinophilia, which was later termed eosinophilic fasciitis (EF) by Rodnan et al.² Eosinophilic fasciitis also is commonly known as diffuse fasciitis with eosinophilia³ or Shulman syndrome.^3,4 It is an inflammatory condition of unknown etiology and pathogenesis, though an underlying autoimmune process has been proposed.^3,5 The disorder is characterized by inflammation and subsequent fibrosis of deep fascia² with variable involvement of the underlying muscle. It often is referred to as a sclerodermalike condition^2,5-8 and is considered to be one of a group of fibrosing connective tissue disorders that may be confused with systemic sclerosis.^3,4,6,9 Although the cause of EF is unknown, more than 50% of cases are associated with vigorous exercise or trauma.³ Other reported triggers and associations include Borrelia burgdorferi infection,^5,6,10 arthropod bites,^5,10 lymphoproliferative and hematologic disorders,^5,6,10 inflammatory arthritis,⁶ morphea,³ thyroid dysfunction,^5,6,10 statins,^5,10 and phenytoin.^5,10

There have been more than 250 cases of EF reported in the literature.³ Some authors report more frequent occurrence in males,^3,4 while others report equal occurrence of disease in both males and females.^5,10 Eosinophilic fasciitis has the highest incidence during the second to sixth decades of life,^3,10 though childhood cases have been reported.^3,11 White individuals appear to be affected most often, but sporadic cases in other ethnic groups also have been reported.³

The clinical presentation of EF frequently is characterized by the rapid onset of erythema, pain, and nonpitting edema of the involved areas.^5,7,10,11 Fatigue and itching also are reported symptoms.¹² A cobblestone texture of the skin may be noted, commonly referred to as the peau d’orange effect.^6,10 Woody induration subsequently develops, which may lead to contracture or limited range of motion.^5,7,11-13 The distal extremities, particularly the forearms and calves, are the most common areas affected by EF.³ There usually is symmetric involvement; however, unilateral cases of EF also have been reported.^3,6,10 Linear indentations may form along the vasculature of the involved areas when the extremities are lifted or extended. These indentations serve to demarcate the underlying muscle groups, forming the groove sign or venous furrowing.^3,5,14 The epidermis is not characteristically involved in EF and wrinkling of the skin can be elicited by pinching,³ which may be helpful in clinically distinguishing EF from scleroderma. Sparing of the digits is another characteristic feature of adult-onset EF.^3,10 However, involvement of the digits resulting in painless contracture has been reported in multiple childhood cases and may represent a phenotype specific to children.¹¹ Involvement of the trunk is less frequently observed but may serve as a poor prognostic indicator; indeed, patients demonstrating young age of onset, morphealike skin sclerosis, and trunk involvement are more likely to develop refractory disease.¹⁵

Eosinophilic fasciitis is characterized by various laboratory abnormalities. Peripheral eosinophilia, hypergammaglobulinemia, elevated sedimentation rate,^{3,6,9,10,13,15} and elevated C-reactive protein^3,6 are commonly reported; however, antinuclear antibody, rheumatoid factor, or antibodies associated with systemic sclerosis are not frequently found.^3,6 There are no laboratory abnormalities required to render a diagnosis of EF, and absence of peripheral eosinophilia has been noted in up to 20% of cases.^3,4 An elevation of creatine kinase or aldolase levels may be present if muscle is involved.^3,6 In general, abnormal laboratory findings have not been found to correlate with disease activity^13,15 and do not appear to have prognostic significance.¹⁵

Biopsy of involved tissue characteristically reveals fascial thickening and fibrosis.^10,13,15 A lymphoplasmacytic infiltrate normally is found in the subcutaneous tissues and fascia and may extend to involve the deeper dermis¹⁵ but usually spares the epidermis.³ It is important to note that increased numbers of eosinophils are not always found in the affected fascia, especially in the later stages of the disease and after steroid treatment.^3,15 Muscle involvement is variable. When muscle is involved, histologic features range from mild inflammation with no evidence of necrosis³ to substantial fibrinoid necrosis.¹³

Magnetic resonance imaging has become a valuable tool in the diagnosis and treatment of EF. Magnetic resonance imaging findings in EF patients typically reveal fascial thickening on T1-weighted images, enhancement after the use of contrast, and hyperintensity on T2-weighted images.⁷ Magnetic resonance imaging has proven useful in supporting clinical diagnosis, monitoring disease activity, identifying optimal biopsy location, and determining response to treatment.^3,7,8,11,13 Magnetic resonance imaging also has been proven to be particularly useful with atypical clinical presentations.⁸ Although deep tissue biopsy remains the gold standard for diagnosis,¹³ magnetic resonance imaging may provide equal or superior diagnostic information.

In general, the prognosis is very good, and the majority of patients will achieve complete remission and cure.³ Up to one-third of patients with EF may experience spontaneous remission without any treatment intervention.¹⁰ The condition generally is highly responsive to oral corticosteroids,^6,10,15 and it has been reported that up to 70% of patients will respond to corticosteroid treatment.³ Most patients respond to a daily dose of prednisone (0.5–1.5 mg/kg), which is continued until clinical response is observed and then followed by a slow steroid taper over a period of several months.³ Patients with persistent fibrosis often require adjunctive therapy in addition to corticosteroids. A variety of adjunctive therapies have been reported to be effective, including hydroxychloroquine sulfate,^{5,10,13,15,16} azathioprine,^15,16 ibuprofen,^10,15 D-penicillamine,^5,15 cyclophosphomide,¹⁵ methotrexate,^6,13,15 cyclosporine,^13,15 psoralen plus UVA,^5,6,15 extracorporeal photochemotherapy,^5,6,10,16 colchicine,⁵ cimetidine,^5,6,10,16 infliximab,^5,6 griseofulvin,¹⁶ ketotifen,¹⁶ sulfasalazine,¹³ and dapsone.¹⁶ Physical therapy has been reported to be useful in preventing permanent joint contractures.^3,5,10,13,16 If treatment fails, the possibility of underlying malignancy must be considered³; however, long courses of treatment are not uncommon. Some patients may need 12 to 18 months of treatment for full response, and even refractory cases are likely to eventually achieve full remission.³