Wells Syndrome

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