Cutis

Granuloma faciale (GF) is an uncommon inflammatory condition characterized by reddish brown papules and plaques that usually involve the facial area. Extrafacial lesions are rare. Histologically, the lesions are marked by leukocytoclastic vasculitis and extensive fibrin deposition. There are a variety of treatment options available for GF.

Granuloma faciale (GF) is an uncommon disease of unknown etiology presenting with asymptomatic cutaneous papules, nodules, and plaques of the face. However, there has been some confusion and evolution of the term granuloma faciale. In 1937, the term eosinophilic granuloma of the skin was used to describe ulcerated lesions of the mouth and anus that were associated with tuberculosis.1,2 Cobane et al3 used the term facial granuloma with eosinophilia. Confusion continued until Lever and Leeper4 subdivided eosinophilic granuloma of the skin into 3 groups. The first group consisted of cases with cutaneous lesions associated with and histologically identical to eosinophilic granuloma of the bone (Langerhans cell histiocytosis). The second group included cases with cutaneous lesions consisting of torpid, asymptomatic purplish patches on the face. The last group was cases with a preponderance of eosinophils in a granulomatous infiltrate that were associated with a variety of diseases.1,4 A case described by Wigley5 in 1945 as Sarcoid of Boeck may, in fact, be the first reported case of GF.6 It was Pinkus,7 however, who in 1952 finally suggested the term granuloma faciale.

GF is characterized by papules, nodules, and plaques that are usually solitary, though multiple or disseminated lesions can be seen.8 The lesions usually are soft, elevated, well-circumscribed nodules ranging in size from millimeters to centimeters.3 The lesions can be shades of red, brown, or purple and may darken with sun exposure. Lesions usually have a smooth surface with follicular accentuation but may have telangiectasias. Ulceration or crusting rarely occurs. These lesions usually develop very slowly and remain unchanged, though occasionally they will involute.6 Tenderness, burning, and pruritus also have been reported.9,10

Although extracutaneous involvement is rare, there are reports of oral mucosa/upper airway involvement. GF can occur in patients of any age, sex, or race but is usually found in middle-aged Caucasian men.1,6,11-13 

Materials and Methods

The clinical presentation and treatment of 38 patients with GF was reviewed. Patient information was obtained from a database covering the past 10 years of patient activity at a large dermatopathology laboratory in Michigan. GF was diagnosed by clinical and histologic criteria including an infiltrate composed of lymphocytes, neutrophils, histiocytes, and eosinophils in the superficial and deep dermis and fibrin deposition within dermal blood vessels confirming the presence of vascular damage. The patients were reviewed according to demographics, location, treatment, and prognosis. Follow-up was obtained through a questionnaire sent to each referring physician. To our knowledge, this review represents the largest series of patients with GF ever described. 

Results

The clinical features of the patients are summarized in the Table. Their ages ranged from 28 to 85 years, with a mean age of 51.9 years for men and 55.4 years for women. The study consisted of 24 men and 14 women, which is in concordance with an early study showing a predominance of GF in men.1 One man and one woman (patients 1 and 7) had multiple lesions. Interestingly, five men (patients 19, 22, 25, 29, and 38) had extrafacial lesions; there are very few reported cases of extrafacial GF.

Comment

GF is characterized by solitary nodules and plaques.1 Most lesions are asymptomatic red, brown, or purple nodules that are soft, elevated, well-circumscribed, and slow to develop (Figure 1).

Lesions usually are seen on the face but may occur elsewhere.14 Particularly, lesions may appear on light-exposed areas, and some lesions are photoexacerbated.10 Sites of predilection are the sides (30%) and tip (7%) of the nose, preauricular area (22%), cheeks (22%), forehead (15%), and helix of the ear (4%).10,15 In a clinical and histopathologic review, Pedace and Perry1 described 21 cases of GF seen at the Mayo Clinic from 1945 to 1965. They noted a predominance of the lesions on the face (nose, forehead, malar, preauricular and postauricular areas, and chin) and less frequently on the forearms and elsewhere.

A review of the literature reveals 14 reported cases of extrafacial involvement.14-18 The clinical aspects of facial and extrafacial lesions are similar.8 Extrafacial lesions usually are found on the trunk and proximal extremities.19 Extrafacial lesions have been reported as isolated findings and in conjunction with facial lesions.17,18 The infrequent reports of extrafacial lesions may reflect either the inconspicuous nature of extrafacial lesions or a failure to examine patients specifically for the lesions.8

Extrafacial GF may be difficult to differentiate from erythema elevatum diutinum (EED). In fact, some authors believe EED and GF represent different parts of the spectrum of the same disease.20 Both are rare chronic forms of cutaneous small vessel vasculitis and may share some pathogenic mechanisms, but there are several clinical and histologic differences. EED is characterized by multiple lesions localized on the extensor surfaces of extremities in an acral, bilateral, and symmetrical distribution. Bulla formation and hemorrhagic crusting may be seen. The trunk is usually spared, and facial lesions are rare. Histopathologic features of EED include a dense superficial and deep polymorphous dermal infiltrate where neutrophils are prominent and eosinophils are scanty or absent. A grenz zone of normal collagen beneath the epidermis rarely exists and the epidermis is not always spared. EED may be associated with systemic conditions, primarily gammopathies. EED shows an excellent response to dapsone.15,21,22

There is a relatively large clinical differential diagnosis for GF including lupus erythematosus, polymorphous light eruption, fixed drug eruption, benign and malignant lymphoid proliferations, sarcoidosis, granuloma annulare, foreign body reaction, tinea faciei, insect bite reaction, juvenile xanthogranuloma, mastocytoma, Spitz nevus, EED, mycosis fungoides, basal cell carcinoma, histiocytosis X, and rosacea.1,6,23-26

There is one case report of Trichophyton rubrum causing histologic changes similar to GF.26 There also has been a case of GF mimicking rhinophyma.27

Histologic findings of GF show a normal epidermis that may be thinned and flattened by underlying infiltrate (Figure 2). There is a narrow grenz zone between the epidermis and the dermal inflammatory infiltrate consisting of lymphocytes, eosinophils, and neutrophils with leukocytoclasis (Figure 3). The infiltrate usually is distributed diffusely in the upper two thirds of the dermis. Fibrin deposition around blood vessels is evidence of vasculitis (Figure 4). In the later fibrotic stage, perivascular fibrin deposition predominates, and the number of inflammatory cells is greatly reduced.6

Microscopically, the primary differential diagnosis is EED, insect bite reaction, cutaneous lymphoma, or leukocytoclastic vasculitis. The exact pathogenesis is unclear, but some consider it a variant of leukocytoclastic vasculitis. Immunoglobulins, fibrin, and complement can be found at the dermal-epidermal junction and around blood vessels on direct immunofluorescence.28-30

GF usually lacks systemic symptoms or laboratory findings other than rare peripheral eosinophilia.31 Immunohistochemical analysis revealed the majority of lymphocytes to be helper T-cell lymphocytes. The cells stained strongly with antibodies against IL-2 receptor and with antibodies to lymphocyte functional antigen-1 α. Overlying keratinocytes did not stain with intracellular adhesion molecule-1 or HLA-DR, which may account for the presence of the grenz zone in GF. These findings suggest that a γ–interferon-mediated process may play some role in the pathogenesis of this disorder.32

GF is known to be resistant to therapy. Numerous physical modalities and medical therapeutics have been tried. Laser therapy, including the CO2,33 argon,34 pulsed dye, and long-pulsed tunable dye lasers,35-38 all have been attempted with varying success. A study showed that lesions treated with a CO2 laser and dermabrasion had a more even texture compared with lesions treated with electrosurgery alone. Healing times were similar between lesions treated with electrosurgery and CO2 laser; however, lesions treated with dermabrasion healed more quickly.39 Studies of patients treated with an argon laser resulted in total resolution of plaques of GF but had a remaining white collagenous scar.34

A case report by Elston37 showed complete resolution of 3 lesions of GF when treated with a pulsed dye laser after the patient failed topical corticosteroids and oral dapsone. A case report by Ammirati et al35 of a patient treated with the 585-nm pulsed dye laser showed clinical eradication of the lesion at 6-year follow-up. Another report by Welsh et al36 showed good results when GF was treated with the pulsed dye laser. Recently, the long-pulsed tunable dye laser was used successfully with no scarring.38 Other modalities that have been used include surgical excision,7,10 dermabrasion, superficial ionizing radiation,6,10 topical psoralen plus UV light,40 cryosurgery,41 intralesional corticosteroids,42 combined cryosurgery and intralesional steroid injection,43 and electrodesiccation.10,39

Medical treatment has included intralesional gold, colchicine, isoniazid, corticosteroids, potassium arsenite, testosterone, antimalarials, dapsone, and clofazimine.9,10,25,27,34,39,44-46 Most medical therapies have shown varying success. No controlled trials are available because of the rarity of the condition.

In our review, most patients were treated with topical and intralesional steroids with varying results that ranged from mild improvement to complete resolution. Because there is a lack of scarring with steroid therapy, we recommend this as a good first-line therapy. Although none of the patients were treated with pulsed dye laser therapy, review of the literature demonstrates favorable results with this treatment modality. Pulsed dye laser should be considered as an alternative therapy.

Granuloma faciale (GF) is an uncommon inflammatory condition characterized by reddish brown papules and plaques that usually involve the facial area. Extrafacial lesions are rare. Histologically, the lesions are marked by leukocytoclastic vasculitis and extensive fibrin deposition. There are a variety of treatment options available for GF.

Granuloma faciale (GF) is an uncommon disease of unknown etiology presenting with asymptomatic cutaneous papules, nodules, and plaques of the face. However, there has been some confusion and evolution of the term granuloma faciale. In 1937, the term eosinophilic granuloma of the skin was used to describe ulcerated lesions of the mouth and anus that were associated with tuberculosis.1,2 Cobane et al3 used the term facial granuloma with eosinophilia. Confusion continued until Lever and Leeper4 subdivided eosinophilic granuloma of the skin into 3 groups. The first group consisted of cases with cutaneous lesions associated with and histologically identical to eosinophilic granuloma of the bone (Langerhans cell histiocytosis). The second group included cases with cutaneous lesions consisting of torpid, asymptomatic purplish patches on the face. The last group was cases with a preponderance of eosinophils in a granulomatous infiltrate that were associated with a variety of diseases.1,4 A case described by Wigley5 in 1945 as Sarcoid of Boeck may, in fact, be the first reported case of GF.6 It was Pinkus,7 however, who in 1952 finally suggested the term granuloma faciale.

GF is characterized by papules, nodules, and plaques that are usually solitary, though multiple or disseminated lesions can be seen.8 The lesions usually are soft, elevated, well-circumscribed nodules ranging in size from millimeters to centimeters.3 The lesions can be shades of red, brown, or purple and may darken with sun exposure. Lesions usually have a smooth surface with follicular accentuation but may have telangiectasias. Ulceration or crusting rarely occurs. These lesions usually develop very slowly and remain unchanged, though occasionally they will involute.6 Tenderness, burning, and pruritus also have been reported.9,10

Although extracutaneous involvement is rare, there are reports of oral mucosa/upper airway involvement. GF can occur in patients of any age, sex, or race but is usually found in middle-aged Caucasian men.1,6,11-13 

Materials and Methods

The clinical presentation and treatment of 38 patients with GF was reviewed. Patient information was obtained from a database covering the past 10 years of patient activity at a large dermatopathology laboratory in Michigan. GF was diagnosed by clinical and histologic criteria including an infiltrate composed of lymphocytes, neutrophils, histiocytes, and eosinophils in the superficial and deep dermis and fibrin deposition within dermal blood vessels confirming the presence of vascular damage. The patients were reviewed according to demographics, location, treatment, and prognosis. Follow-up was obtained through a questionnaire sent to each referring physician. To our knowledge, this review represents the largest series of patients with GF ever described. 

Results

The clinical features of the patients are summarized in the Table. Their ages ranged from 28 to 85 years, with a mean age of 51.9 years for men and 55.4 years for women. The study consisted of 24 men and 14 women, which is in concordance with an early study showing a predominance of GF in men.1 One man and one woman (patients 1 and 7) had multiple lesions. Interestingly, five men (patients 19, 22, 25, 29, and 38) had extrafacial lesions; there are very few reported cases of extrafacial GF.

Comment

GF is characterized by solitary nodules and plaques.1 Most lesions are asymptomatic red, brown, or purple nodules that are soft, elevated, well-circumscribed, and slow to develop (Figure 1).

Lesions usually are seen on the face but may occur elsewhere.14 Particularly, lesions may appear on light-exposed areas, and some lesions are photoexacerbated.10 Sites of predilection are the sides (30%) and tip (7%) of the nose, preauricular area (22%), cheeks (22%), forehead (15%), and helix of the ear (4%).10,15 In a clinical and histopathologic review, Pedace and Perry1 described 21 cases of GF seen at the Mayo Clinic from 1945 to 1965. They noted a predominance of the lesions on the face (nose, forehead, malar, preauricular and postauricular areas, and chin) and less frequently on the forearms and elsewhere.

A review of the literature reveals 14 reported cases of extrafacial involvement.14-18 The clinical aspects of facial and extrafacial lesions are similar.8 Extrafacial lesions usually are found on the trunk and proximal extremities.19 Extrafacial lesions have been reported as isolated findings and in conjunction with facial lesions.17,18 The infrequent reports of extrafacial lesions may reflect either the inconspicuous nature of extrafacial lesions or a failure to examine patients specifically for the lesions.8

Extrafacial GF may be difficult to differentiate from erythema elevatum diutinum (EED). In fact, some authors believe EED and GF represent different parts of the spectrum of the same disease.20 Both are rare chronic forms of cutaneous small vessel vasculitis and may share some pathogenic mechanisms, but there are several clinical and histologic differences. EED is characterized by multiple lesions localized on the extensor surfaces of extremities in an acral, bilateral, and symmetrical distribution. Bulla formation and hemorrhagic crusting may be seen. The trunk is usually spared, and facial lesions are rare. Histopathologic features of EED include a dense superficial and deep polymorphous dermal infiltrate where neutrophils are prominent and eosinophils are scanty or absent. A grenz zone of normal collagen beneath the epidermis rarely exists and the epidermis is not always spared. EED may be associated with systemic conditions, primarily gammopathies. EED shows an excellent response to dapsone.15,21,22

There is a relatively large clinical differential diagnosis for GF including lupus erythematosus, polymorphous light eruption, fixed drug eruption, benign and malignant lymphoid proliferations, sarcoidosis, granuloma annulare, foreign body reaction, tinea faciei, insect bite reaction, juvenile xanthogranuloma, mastocytoma, Spitz nevus, EED, mycosis fungoides, basal cell carcinoma, histiocytosis X, and rosacea.1,6,23-26

There is one case report of Trichophyton rubrum causing histologic changes similar to GF.26 There also has been a case of GF mimicking rhinophyma.27

Histologic findings of GF show a normal epidermis that may be thinned and flattened by underlying infiltrate (Figure 2). There is a narrow grenz zone between the epidermis and the dermal inflammatory infiltrate consisting of lymphocytes, eosinophils, and neutrophils with leukocytoclasis (Figure 3). The infiltrate usually is distributed diffusely in the upper two thirds of the dermis. Fibrin deposition around blood vessels is evidence of vasculitis (Figure 4). In the later fibrotic stage, perivascular fibrin deposition predominates, and the number of inflammatory cells is greatly reduced.6

Microscopically, the primary differential diagnosis is EED, insect bite reaction, cutaneous lymphoma, or leukocytoclastic vasculitis. The exact pathogenesis is unclear, but some consider it a variant of leukocytoclastic vasculitis. Immunoglobulins, fibrin, and complement can be found at the dermal-epidermal junction and around blood vessels on direct immunofluorescence.28-30

GF usually lacks systemic symptoms or laboratory findings other than rare peripheral eosinophilia.31 Immunohistochemical analysis revealed the majority of lymphocytes to be helper T-cell lymphocytes. The cells stained strongly with antibodies against IL-2 receptor and with antibodies to lymphocyte functional antigen-1 α. Overlying keratinocytes did not stain with intracellular adhesion molecule-1 or HLA-DR, which may account for the presence of the grenz zone in GF. These findings suggest that a γ–interferon-mediated process may play some role in the pathogenesis of this disorder.32

GF is known to be resistant to therapy. Numerous physical modalities and medical therapeutics have been tried. Laser therapy, including the CO2,33 argon,34 pulsed dye, and long-pulsed tunable dye lasers,35-38 all have been attempted with varying success. A study showed that lesions treated with a CO2 laser and dermabrasion had a more even texture compared with lesions treated with electrosurgery alone. Healing times were similar between lesions treated with electrosurgery and CO2 laser; however, lesions treated with dermabrasion healed more quickly.39 Studies of patients treated with an argon laser resulted in total resolution of plaques of GF but had a remaining white collagenous scar.34

A case report by Elston37 showed complete resolution of 3 lesions of GF when treated with a pulsed dye laser after the patient failed topical corticosteroids and oral dapsone. A case report by Ammirati et al35 of a patient treated with the 585-nm pulsed dye laser showed clinical eradication of the lesion at 6-year follow-up. Another report by Welsh et al36 showed good results when GF was treated with the pulsed dye laser. Recently, the long-pulsed tunable dye laser was used successfully with no scarring.38 Other modalities that have been used include surgical excision,7,10 dermabrasion, superficial ionizing radiation,6,10 topical psoralen plus UV light,40 cryosurgery,41 intralesional corticosteroids,42 combined cryosurgery and intralesional steroid injection,43 and electrodesiccation.10,39

Medical treatment has included intralesional gold, colchicine, isoniazid, corticosteroids, potassium arsenite, testosterone, antimalarials, dapsone, and clofazimine.9,10,25,27,34,39,44-46 Most medical therapies have shown varying success. No controlled trials are available because of the rarity of the condition.

In our review, most patients were treated with topical and intralesional steroids with varying results that ranged from mild improvement to complete resolution. Because there is a lack of scarring with steroid therapy, we recommend this as a good first-line therapy. Although none of the patients were treated with pulsed dye laser therapy, review of the literature demonstrates favorable results with this treatment modality. Pulsed dye laser should be considered as an alternative therapy.

Granuloma faciale (GF) is an uncommon inflammatory condition characterized by reddish brown papules and plaques that usually involve the facial area. Extrafacial lesions are rare. Histologically, the lesions are marked by leukocytoclastic vasculitis and extensive fibrin deposition. There are a variety of treatment options available for GF.

Granuloma faciale (GF) is an uncommon disease of unknown etiology presenting with asymptomatic cutaneous papules, nodules, and plaques of the face. However, there has been some confusion and evolution of the term granuloma faciale. In 1937, the term eosinophilic granuloma of the skin was used to describe ulcerated lesions of the mouth and anus that were associated with tuberculosis.1,2 Cobane et al3 used the term facial granuloma with eosinophilia. Confusion continued until Lever and Leeper4 subdivided eosinophilic granuloma of the skin into 3 groups. The first group consisted of cases with cutaneous lesions associated with and histologically identical to eosinophilic granuloma of the bone (Langerhans cell histiocytosis). The second group included cases with cutaneous lesions consisting of torpid, asymptomatic purplish patches on the face. The last group was cases with a preponderance of eosinophils in a granulomatous infiltrate that were associated with a variety of diseases.1,4 A case described by Wigley5 in 1945 as Sarcoid of Boeck may, in fact, be the first reported case of GF.6 It was Pinkus,7 however, who in 1952 finally suggested the term granuloma faciale.

GF is characterized by papules, nodules, and plaques that are usually solitary, though multiple or disseminated lesions can be seen.8 The lesions usually are soft, elevated, well-circumscribed nodules ranging in size from millimeters to centimeters.3 The lesions can be shades of red, brown, or purple and may darken with sun exposure. Lesions usually have a smooth surface with follicular accentuation but may have telangiectasias. Ulceration or crusting rarely occurs. These lesions usually develop very slowly and remain unchanged, though occasionally they will involute.6 Tenderness, burning, and pruritus also have been reported.9,10

Although extracutaneous involvement is rare, there are reports of oral mucosa/upper airway involvement. GF can occur in patients of any age, sex, or race but is usually found in middle-aged Caucasian men.1,6,11-13 

Materials and Methods

The clinical presentation and treatment of 38 patients with GF was reviewed. Patient information was obtained from a database covering the past 10 years of patient activity at a large dermatopathology laboratory in Michigan. GF was diagnosed by clinical and histologic criteria including an infiltrate composed of lymphocytes, neutrophils, histiocytes, and eosinophils in the superficial and deep dermis and fibrin deposition within dermal blood vessels confirming the presence of vascular damage. The patients were reviewed according to demographics, location, treatment, and prognosis. Follow-up was obtained through a questionnaire sent to each referring physician. To our knowledge, this review represents the largest series of patients with GF ever described. 

Results

The clinical features of the patients are summarized in the Table. Their ages ranged from 28 to 85 years, with a mean age of 51.9 years for men and 55.4 years for women. The study consisted of 24 men and 14 women, which is in concordance with an early study showing a predominance of GF in men.1 One man and one woman (patients 1 and 7) had multiple lesions. Interestingly, five men (patients 19, 22, 25, 29, and 38) had extrafacial lesions; there are very few reported cases of extrafacial GF.

Comment

GF is characterized by solitary nodules and plaques.1 Most lesions are asymptomatic red, brown, or purple nodules that are soft, elevated, well-circumscribed, and slow to develop (Figure 1).

Lesions usually are seen on the face but may occur elsewhere.14 Particularly, lesions may appear on light-exposed areas, and some lesions are photoexacerbated.10 Sites of predilection are the sides (30%) and tip (7%) of the nose, preauricular area (22%), cheeks (22%), forehead (15%), and helix of the ear (4%).10,15 In a clinical and histopathologic review, Pedace and Perry1 described 21 cases of GF seen at the Mayo Clinic from 1945 to 1965. They noted a predominance of the lesions on the face (nose, forehead, malar, preauricular and postauricular areas, and chin) and less frequently on the forearms and elsewhere.

A review of the literature reveals 14 reported cases of extrafacial involvement.14-18 The clinical aspects of facial and extrafacial lesions are similar.8 Extrafacial lesions usually are found on the trunk and proximal extremities.19 Extrafacial lesions have been reported as isolated findings and in conjunction with facial lesions.17,18 The infrequent reports of extrafacial lesions may reflect either the inconspicuous nature of extrafacial lesions or a failure to examine patients specifically for the lesions.8

Extrafacial GF may be difficult to differentiate from erythema elevatum diutinum (EED). In fact, some authors believe EED and GF represent different parts of the spectrum of the same disease.20 Both are rare chronic forms of cutaneous small vessel vasculitis and may share some pathogenic mechanisms, but there are several clinical and histologic differences. EED is characterized by multiple lesions localized on the extensor surfaces of extremities in an acral, bilateral, and symmetrical distribution. Bulla formation and hemorrhagic crusting may be seen. The trunk is usually spared, and facial lesions are rare. Histopathologic features of EED include a dense superficial and deep polymorphous dermal infiltrate where neutrophils are prominent and eosinophils are scanty or absent. A grenz zone of normal collagen beneath the epidermis rarely exists and the epidermis is not always spared. EED may be associated with systemic conditions, primarily gammopathies. EED shows an excellent response to dapsone.15,21,22

There is a relatively large clinical differential diagnosis for GF including lupus erythematosus, polymorphous light eruption, fixed drug eruption, benign and malignant lymphoid proliferations, sarcoidosis, granuloma annulare, foreign body reaction, tinea faciei, insect bite reaction, juvenile xanthogranuloma, mastocytoma, Spitz nevus, EED, mycosis fungoides, basal cell carcinoma, histiocytosis X, and rosacea.1,6,23-26

There is one case report of Trichophyton rubrum causing histologic changes similar to GF.26 There also has been a case of GF mimicking rhinophyma.27

Histologic findings of GF show a normal epidermis that may be thinned and flattened by underlying infiltrate (Figure 2). There is a narrow grenz zone between the epidermis and the dermal inflammatory infiltrate consisting of lymphocytes, eosinophils, and neutrophils with leukocytoclasis (Figure 3). The infiltrate usually is distributed diffusely in the upper two thirds of the dermis. Fibrin deposition around blood vessels is evidence of vasculitis (Figure 4). In the later fibrotic stage, perivascular fibrin deposition predominates, and the number of inflammatory cells is greatly reduced.6

Microscopically, the primary differential diagnosis is EED, insect bite reaction, cutaneous lymphoma, or leukocytoclastic vasculitis. The exact pathogenesis is unclear, but some consider it a variant of leukocytoclastic vasculitis. Immunoglobulins, fibrin, and complement can be found at the dermal-epidermal junction and around blood vessels on direct immunofluorescence.28-30

GF usually lacks systemic symptoms or laboratory findings other than rare peripheral eosinophilia.31 Immunohistochemical analysis revealed the majority of lymphocytes to be helper T-cell lymphocytes. The cells stained strongly with antibodies against IL-2 receptor and with antibodies to lymphocyte functional antigen-1 α. Overlying keratinocytes did not stain with intracellular adhesion molecule-1 or HLA-DR, which may account for the presence of the grenz zone in GF. These findings suggest that a γ–interferon-mediated process may play some role in the pathogenesis of this disorder.32

GF is known to be resistant to therapy. Numerous physical modalities and medical therapeutics have been tried. Laser therapy, including the CO2,33 argon,34 pulsed dye, and long-pulsed tunable dye lasers,35-38 all have been attempted with varying success. A study showed that lesions treated with a CO2 laser and dermabrasion had a more even texture compared with lesions treated with electrosurgery alone. Healing times were similar between lesions treated with electrosurgery and CO2 laser; however, lesions treated with dermabrasion healed more quickly.39 Studies of patients treated with an argon laser resulted in total resolution of plaques of GF but had a remaining white collagenous scar.34

A case report by Elston37 showed complete resolution of 3 lesions of GF when treated with a pulsed dye laser after the patient failed topical corticosteroids and oral dapsone. A case report by Ammirati et al35 of a patient treated with the 585-nm pulsed dye laser showed clinical eradication of the lesion at 6-year follow-up. Another report by Welsh et al36 showed good results when GF was treated with the pulsed dye laser. Recently, the long-pulsed tunable dye laser was used successfully with no scarring.38 Other modalities that have been used include surgical excision,7,10 dermabrasion, superficial ionizing radiation,6,10 topical psoralen plus UV light,40 cryosurgery,41 intralesional corticosteroids,42 combined cryosurgery and intralesional steroid injection,43 and electrodesiccation.10,39

Medical treatment has included intralesional gold, colchicine, isoniazid, corticosteroids, potassium arsenite, testosterone, antimalarials, dapsone, and clofazimine.9,10,25,27,34,39,44-46 Most medical therapies have shown varying success. No controlled trials are available because of the rarity of the condition.

In our review, most patients were treated with topical and intralesional steroids with varying results that ranged from mild improvement to complete resolution. Because there is a lack of scarring with steroid therapy, we recommend this as a good first-line therapy. Although none of the patients were treated with pulsed dye laser therapy, review of the literature demonstrates favorable results with this treatment modality. Pulsed dye laser should be considered as an alternative therapy.

Wells syndrome, or eosinophilic cellulitis, is a rare inflammatory dermatosis first described by Wells in 1971.1,2 More than 100 clinical cases have been described in the medical literature, but only 18 of these cases have occurred in children.3 The syndrome is characterized by recurrent cutaneous erythema and edema, peripheral eosinophilia, and a typical histopathology. 

Case Report

A 17-month-old child presented with a 2-month recurrent cutaneous rash on all 4 extremities. The eruption consisted of red and painful papules that progressively increased in size and evolved over a period of 7 days into thickened nodules. Lesions of various stages of development were present at the same time. The patient was irritable during this time, but not febrile. Before presenting to us, the patient had been treated with oral antibiotics, which proved to be ineffective.

Physical examination revealed mildly fluctuant, violaceous, indurated plaques on the palms and soles bilaterally and on the dorsum of the left foot (Figure 1). All lesions were tender to palpation. Significant laboratory findings included a white blood cell count of 15.9x103/μL with 14% eosinophils. Biopsy results of the 5x5-mm plaque on the dorsum of the left foot showed mixed dermal infiltrate with marked eosinophilia and collagen degenerative changes with flame figures (Figure 2). Eosinophilic cellulitis was diagnosed, and the patient was started on prednisone 1 mg/kg daily. The lesions resolved after 3 weeks of corticosteroid therapy.

Comment

Although the etiology of Wells syndrome is not clearly defined, it is believed to be a hypersensitivity reaction to various triggering agents (Table).1-14 In the majority of cases, however, the inciting agent remains unknown, as was the case with our patient. Some authors define Wells syndrome as a clinical entity,9 while others view it strictly as a histopathologic reaction pattern.5,12

Patients with eosinophilic cellulitis present with focal edema and annular or circinate, erythematous, infiltrated plaques with a sharp, rosy, or violaceous border. The lesions, commonly located on the extremities and trunk, may progress to vesicles and bullae. Pruritus, pain, and a burning sensation can be present before or during the presence of the lesions; however, systemic symptoms (malaise, fever) are rare.9 Peripheral eosinophilia is detected in approximately half of the patients.1,2 After a period of days to several weeks, these lesions evolve to bluish gray, indurated lesions, and the skin eventually returns to normal without scar formation. In most cases, new lesions erupt after the initial outbreak.

At their onset, the lesions of Wells syndrome may be clinically mistaken for erysipelas or infectious cellulitis; however, a course of antibiotics will fail to treat the symptoms. Less common diseases, such as allergic granulomatosis of Churg-Strauss and hypereosinophilic syndromes, also may be suspected. The absence of necrotizing vasculitis on biopsy and a negative serum antineutrophilic cytoplasmic antibody, however, excludes the diagnosis of Churg-Strauss syndrome.15 A diagnosis of hypereosinophilic syndrome requires evidence of visceral involvement and a sustained eosinophilia for more than 6 months.16 The hyperpigmented and indurated lesions of late-stage Wells syndrome may resemble the appearance of morphea.

The diagnosis of Wells syndrome usually is made by skin biopsy. Wells1,17 described 3 sequential histopathologic stages of the syndrome. The acute, or cellulitic, stage is identified by both edema and an eosinophilic infiltrate (interstitially and perivascularly) in the dermis, especially the reticular dermis. The subacute stage, also known as granulomatous dermatitis, is characterized by the formation of flame figures, which are collections of eosinophils, histiocytes, and foreign body giant cells encircling a core of degenerated collagen fibers in a background of granulomatous inflammation. Immunofluorescence localizes major basic protein within the flame figures, indicating eosinophilic degranulation.7 Although highly characteristic of Wells syndrome, flame figures are not pathognomonic for the disease and also can be seen in bullous pemphigoid, gestational herpes, insect bites, and fungal and parasitic infections.2,5,18 The last stage is the resolution stage, which shows decreased numbers of eosinophils within the granulomatous inflammation.

The recommended treatment for Wells syndrome is a tapering course of systemic corticosteroids, usually prednisone at a dose of 10 to 80 mg/day.1,3,8,19 One study reported that even low-dose (5 mg) prednisone every other day was efficacious in the treatment of Wells syndrome.20 On rare occasions, patients treated with dapsone have shown clinical improvement.21 Most recently, psoralen-UVA phototherapy has had initial success in clearing the lesions of Wells syndrome.22 The effectiveness of treatment is confounded by the fact that the lesions resolve within 6 to 8 weeks with or without therapy. Although the syndrome recurs sporadically, spontaneous resolution occurs in all patients after a period of months to several years.9,20 

Wells syndrome, or eosinophilic cellulitis, is a rare inflammatory dermatosis first described by Wells in 1971.1,2 More than 100 clinical cases have been described in the medical literature, but only 18 of these cases have occurred in children.3 The syndrome is characterized by recurrent cutaneous erythema and edema, peripheral eosinophilia, and a typical histopathology. 

Case Report

A 17-month-old child presented with a 2-month recurrent cutaneous rash on all 4 extremities. The eruption consisted of red and painful papules that progressively increased in size and evolved over a period of 7 days into thickened nodules. Lesions of various stages of development were present at the same time. The patient was irritable during this time, but not febrile. Before presenting to us, the patient had been treated with oral antibiotics, which proved to be ineffective.

Physical examination revealed mildly fluctuant, violaceous, indurated plaques on the palms and soles bilaterally and on the dorsum of the left foot (Figure 1). All lesions were tender to palpation. Significant laboratory findings included a white blood cell count of 15.9x103/μL with 14% eosinophils. Biopsy results of the 5x5-mm plaque on the dorsum of the left foot showed mixed dermal infiltrate with marked eosinophilia and collagen degenerative changes with flame figures (Figure 2). Eosinophilic cellulitis was diagnosed, and the patient was started on prednisone 1 mg/kg daily. The lesions resolved after 3 weeks of corticosteroid therapy.

Comment

Although the etiology of Wells syndrome is not clearly defined, it is believed to be a hypersensitivity reaction to various triggering agents (Table).1-14 In the majority of cases, however, the inciting agent remains unknown, as was the case with our patient. Some authors define Wells syndrome as a clinical entity,9 while others view it strictly as a histopathologic reaction pattern.5,12

Patients with eosinophilic cellulitis present with focal edema and annular or circinate, erythematous, infiltrated plaques with a sharp, rosy, or violaceous border. The lesions, commonly located on the extremities and trunk, may progress to vesicles and bullae. Pruritus, pain, and a burning sensation can be present before or during the presence of the lesions; however, systemic symptoms (malaise, fever) are rare.9 Peripheral eosinophilia is detected in approximately half of the patients.1,2 After a period of days to several weeks, these lesions evolve to bluish gray, indurated lesions, and the skin eventually returns to normal without scar formation. In most cases, new lesions erupt after the initial outbreak.

At their onset, the lesions of Wells syndrome may be clinically mistaken for erysipelas or infectious cellulitis; however, a course of antibiotics will fail to treat the symptoms. Less common diseases, such as allergic granulomatosis of Churg-Strauss and hypereosinophilic syndromes, also may be suspected. The absence of necrotizing vasculitis on biopsy and a negative serum antineutrophilic cytoplasmic antibody, however, excludes the diagnosis of Churg-Strauss syndrome.15 A diagnosis of hypereosinophilic syndrome requires evidence of visceral involvement and a sustained eosinophilia for more than 6 months.16 The hyperpigmented and indurated lesions of late-stage Wells syndrome may resemble the appearance of morphea.

The diagnosis of Wells syndrome usually is made by skin biopsy. Wells1,17 described 3 sequential histopathologic stages of the syndrome. The acute, or cellulitic, stage is identified by both edema and an eosinophilic infiltrate (interstitially and perivascularly) in the dermis, especially the reticular dermis. The subacute stage, also known as granulomatous dermatitis, is characterized by the formation of flame figures, which are collections of eosinophils, histiocytes, and foreign body giant cells encircling a core of degenerated collagen fibers in a background of granulomatous inflammation. Immunofluorescence localizes major basic protein within the flame figures, indicating eosinophilic degranulation.7 Although highly characteristic of Wells syndrome, flame figures are not pathognomonic for the disease and also can be seen in bullous pemphigoid, gestational herpes, insect bites, and fungal and parasitic infections.2,5,18 The last stage is the resolution stage, which shows decreased numbers of eosinophils within the granulomatous inflammation.

The recommended treatment for Wells syndrome is a tapering course of systemic corticosteroids, usually prednisone at a dose of 10 to 80 mg/day.1,3,8,19 One study reported that even low-dose (5 mg) prednisone every other day was efficacious in the treatment of Wells syndrome.20 On rare occasions, patients treated with dapsone have shown clinical improvement.21 Most recently, psoralen-UVA phototherapy has had initial success in clearing the lesions of Wells syndrome.22 The effectiveness of treatment is confounded by the fact that the lesions resolve within 6 to 8 weeks with or without therapy. Although the syndrome recurs sporadically, spontaneous resolution occurs in all patients after a period of months to several years.9,20 

Wells syndrome, or eosinophilic cellulitis, is a rare inflammatory dermatosis first described by Wells in 1971.1,2 More than 100 clinical cases have been described in the medical literature, but only 18 of these cases have occurred in children.3 The syndrome is characterized by recurrent cutaneous erythema and edema, peripheral eosinophilia, and a typical histopathology. 

Case Report

A 17-month-old child presented with a 2-month recurrent cutaneous rash on all 4 extremities. The eruption consisted of red and painful papules that progressively increased in size and evolved over a period of 7 days into thickened nodules. Lesions of various stages of development were present at the same time. The patient was irritable during this time, but not febrile. Before presenting to us, the patient had been treated with oral antibiotics, which proved to be ineffective.

Physical examination revealed mildly fluctuant, violaceous, indurated plaques on the palms and soles bilaterally and on the dorsum of the left foot (Figure 1). All lesions were tender to palpation. Significant laboratory findings included a white blood cell count of 15.9x103/μL with 14% eosinophils. Biopsy results of the 5x5-mm plaque on the dorsum of the left foot showed mixed dermal infiltrate with marked eosinophilia and collagen degenerative changes with flame figures (Figure 2). Eosinophilic cellulitis was diagnosed, and the patient was started on prednisone 1 mg/kg daily. The lesions resolved after 3 weeks of corticosteroid therapy.

Comment

Although the etiology of Wells syndrome is not clearly defined, it is believed to be a hypersensitivity reaction to various triggering agents (Table).1-14 In the majority of cases, however, the inciting agent remains unknown, as was the case with our patient. Some authors define Wells syndrome as a clinical entity,9 while others view it strictly as a histopathologic reaction pattern.5,12

Patients with eosinophilic cellulitis present with focal edema and annular or circinate, erythematous, infiltrated plaques with a sharp, rosy, or violaceous border. The lesions, commonly located on the extremities and trunk, may progress to vesicles and bullae. Pruritus, pain, and a burning sensation can be present before or during the presence of the lesions; however, systemic symptoms (malaise, fever) are rare.9 Peripheral eosinophilia is detected in approximately half of the patients.1,2 After a period of days to several weeks, these lesions evolve to bluish gray, indurated lesions, and the skin eventually returns to normal without scar formation. In most cases, new lesions erupt after the initial outbreak.

At their onset, the lesions of Wells syndrome may be clinically mistaken for erysipelas or infectious cellulitis; however, a course of antibiotics will fail to treat the symptoms. Less common diseases, such as allergic granulomatosis of Churg-Strauss and hypereosinophilic syndromes, also may be suspected. The absence of necrotizing vasculitis on biopsy and a negative serum antineutrophilic cytoplasmic antibody, however, excludes the diagnosis of Churg-Strauss syndrome.15 A diagnosis of hypereosinophilic syndrome requires evidence of visceral involvement and a sustained eosinophilia for more than 6 months.16 The hyperpigmented and indurated lesions of late-stage Wells syndrome may resemble the appearance of morphea.

The diagnosis of Wells syndrome usually is made by skin biopsy. Wells1,17 described 3 sequential histopathologic stages of the syndrome. The acute, or cellulitic, stage is identified by both edema and an eosinophilic infiltrate (interstitially and perivascularly) in the dermis, especially the reticular dermis. The subacute stage, also known as granulomatous dermatitis, is characterized by the formation of flame figures, which are collections of eosinophils, histiocytes, and foreign body giant cells encircling a core of degenerated collagen fibers in a background of granulomatous inflammation. Immunofluorescence localizes major basic protein within the flame figures, indicating eosinophilic degranulation.7 Although highly characteristic of Wells syndrome, flame figures are not pathognomonic for the disease and also can be seen in bullous pemphigoid, gestational herpes, insect bites, and fungal and parasitic infections.2,5,18 The last stage is the resolution stage, which shows decreased numbers of eosinophils within the granulomatous inflammation.

The recommended treatment for Wells syndrome is a tapering course of systemic corticosteroids, usually prednisone at a dose of 10 to 80 mg/day.1,3,8,19 One study reported that even low-dose (5 mg) prednisone every other day was efficacious in the treatment of Wells syndrome.20 On rare occasions, patients treated with dapsone have shown clinical improvement.21 Most recently, psoralen-UVA phototherapy has had initial success in clearing the lesions of Wells syndrome.22 The effectiveness of treatment is confounded by the fact that the lesions resolve within 6 to 8 weeks with or without therapy. Although the syndrome recurs sporadically, spontaneous resolution occurs in all patients after a period of months to several years.9,20