Recurrent Bilaterally Symmetrical Bullous Sweet's Syndrome: A Rare and Confusing Entity.

A rare presentation of Sweet's syndrome (SS) (acute febrile neutrophilic dermatosis) is being reported in a 28-year-old man from India. I report a rare presentation of SS that consisted of bilaterally symmetrical, bullous lesions on both forearms with a seasonal recurrence. A thorough work-up for the usual conditions predisposing to or leading to SS did not throw any light on the etiology. After failing treatment with prednisolone alone we added indomethacin, and he responded to the combination in a matter of days with complete clearance of lesions.

What was known?

Sweet's syndrome (SS) also known as acute febrile neutrophilic dermatosis, is characterized by tender erythematous lesions on the skin, fever with leukocytosis showing a predominance of neutrophils, a raised erythrocyte sedimentation rate and a biopsy showing mature neutrophils in the upper and mid dermis, and, generally, absence of vasculitis. It has been described mainly under three headings. Idiopathic or classical SS, SS associated with a malignancy and SS associated with drug intake

Introduction

Localised Sweet's syndrome (SS) with recurrent, bilaterally symmetrical bullous lesions is rare and can be a confusing clinical entity. A case is being described where no specific cause was identified. He also did not have fever, leukocytosis or neutrophilia in the beginning of the disease, but developed them later on. He was treated with prednisolone and then a combination of prednisolone with indomethacin, which led to complete resolution.

Case Report

A 28-year-old man presented in this clinic with a blistering eruption on the ventrolateral aspect of his mid forearms, which he noticed about 10 days back. A similar eruption appeared every monsoon during the rainy season, and resolved in about 1 month or so, but this time it was more severe and very painful. On examination, the man was of thin built, had advanced androgenetic alopecia and looked ill. He was not febrile, but was in pain. There were bilaterally symmetrically located lesions on the ventral aspect of the mid forearms comprising well-circumscribed, painful erythematous plaques studded with crusts and bullae [Figure 1]. There was nothing to suggest contact dermatitis or a history of drug intake. Relevant investigations revealed nothing abnormal except a borderline total leukocyte count and neutrophil count. A pharmacist by profession, he had taken Cefadroxil, azithromycin and ciprofloxacin along with 10 mg prednisolone randomly without any benefit. He was given a full course of 625 mg of clavulinate-potentiated amoxicillin twice daily with paracetamol 500 mg three times a day and 30 mg prednisolone once a day for 5 days, but did not show improvement. When he came on the fifth day, he had developed fever, had severe pain and was unwell. Hb was 13 gm, total count was 12000 with 88% polymorphs, ESR was 15 mm, kidney and liver functions were normal and his urine was normal. A punch biopsy revealed spongiotic epidermis with a mild dermal edema. There were large aggregates of neutrophils in the upper and mid dermis showing nuclear dust [Figure 2]. Blood vessels were not affected and there was no sign of vasculitis [Figure 3]. Based on all this, a diagnosis of recurrent localized bullous SS presenting as bilaterally symmetrical erythematous plaques studded with bullae mimicking contact dermatitis or fixed drug eruption was made. Hematologic and solid organ malignancies were ruled out keeping in mind financial constraints. This was done owing to the association of the vesicobullous variant of SS with such underlying malignancies. Prednisolone was continued and indomethacin tablets were started at the dose of 150 mg per day with food, to which he responded within 5 days with complete resolution of lesions, no fever and normal hematologic parameters [Figure 4].

Figure 1

Bilaterally symmetrical erythematous plaques with ulcerated bullae

Figure 2

Hematoxylin and eosin, 10×, scanner view showing diffuse infiltrate in the upper and mid dermis

Figure 3

Hematoxylin and eosin, 100×, high power view showing spongiosis, dermal edema, neutrophils and absence of vasculitis

Figure 4

Complete resolution of lesions in 2 weeks

Discussion

Sweet's syndrome also known as acute febrile neutrophilic dermatosis, is characterized by tender erythematous lesions on the skin, fever with leukocytosis showing a predominance of neutrophils, a raised erythrocyte sedimentation rate and a biopsy showing mature neutrophils in the upper and mid dermis, and, generally, absence of vasculitis.[1-5] It has been described mainly under three headings. Idiopathic or classical SS, SS associated with a malignancy and SS associated with drug intake.[23] Localized SS is a rare variant and there has been a special interest in describing its occurrence on the hands as “neutrophilic dermatosis of dorsal hands (NDDH).”[6-8] It would be interesting to see whether the bilaterally symmetrical lesions localized to the forearms are a distributional variant of NDDH.

This seems to be a rare and interesting case because of its bilaterally symmetrical localized distribution of ulcerated and crusted plaques studded with bullae and a characteristic histology of SS A detailed examination failed to detect infection. It is possible that he may have been suffering from a recurrent viral infection during the monsoon seasons, which would then explain the post-infection occurrence of SS.[239] The classical idiopathic form has a female predilection. Because SS occurs in males as frequently as in females, when associated with cancer, we diligently tried to rule out malignancy.[2310] An exhaustive review of about 15 detailed studies of malignancy-associated SS showed that 21% of the patients had a hematologic or solid organ malignancy.[10] A detailed work up with relevant hematologic investigations, X-ray of chest and abdomen and ultrasonography of the abdomen and pelvis did not reveal anything. Carcinoembryonic antigen (CEA) was normal. The most frequently associated hematologic malignancy in association with SS is acute myelogenous leukemia. Solid tumor malignancies most related with SS are those of genitourinary or gastrointestinal tract in males. A detailed history of drug intake was negative. Vesicles as well as bullae are seen in SS and ulcerated bullous lesions mimicking pyoderma gangrenosum have been described in malignancy-associated SS.[10-12] Recurrence as seen in our patient has been described in approximately 1/3rd to 2/3rd of patients.[23] Patients may be visibly ill with fever but there is no uniform pattern. It can precede the eruption, may occur with it or be present throughout the episode. Absence of fever in malignancy-associated SS has also been demonstrated. Our patient was afebrile during the first consultation but developed fever subsequently. The biopsy showed a typical diffuse infiltrate of mature neutrophils and dermal edema without primary vasculitis as is the case in the majority of cases.[2-5] However, in some cases of SS, perivascular distribution of neutrophils and leukocytoclasia have been demonstrated.[2-5]

The patient has been explained the importance of a regular follow-up with routine blood examination twice a year as there are reports of hematologic malignancies being detected as long as 11 years after the skin lesions.[310]

SS is known to respond dramatically to oral steroids. Second-line therapies include potassium iodide, colchicine, indomethacin, dapsone, clofazimine, doxycline and metronidazole. This patient did not respond to 30 mg oral prednisolone initially but responded dramatically with complete resolution of lesions in 5 days when 150 mg indomethacin was added.

In conclusion, a recurrent localized bullous variant of SS presenting with lesions not associated with an overt infection, malignancy or drug intake is being reported bilaterally symmetrically on the forearms.

What is new?

Bilaterally symmetrical bullous crusted Sweet's syndrome masquerading as a contact dermatitis, photodermatitis or fixed drug reaction can be a diagnostic dilemma. No overt cause like infection, malignancy or drug intake was identified.