Dermatology Online Journal

Chronic, recurrent neutrophilic dermatosis: A case report
Alok Vij MD¹, Gunjan M Modi MD¹, Pitiporn Suwattee MD², Clay J Cockerell MD², Sylvia Hsu MD¹
Dermatology Online Journal 16 (10): 1

1. Department of Dermatology, Baylor College of Medicine, Houston, Texas
2. Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas

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Abstract

Sweet syndrome is a reactive neutrophilic dermatosis that develops in response to various systemic illnesses. The cutaneous manifestations include an acute eruption of painful, edematous papules, plaques, pustules, or vesicles associated with fever and other constitutional symptoms. Although the etiology cannot always be determined, Sweet syndrome most commonly arises in reaction to systemic illnesses, such as infections, inflammatory bowel disease, medications, and malignancies. We report a case of chronic, recurrent Sweet syndrome lasting over 15 years in a patient with no identifiable underlying illness.

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Case presentation

A 43-year-old male with no significant past medical history presented to his local dermatologist in 1995 with a painful, enlarging papule on his left ankle after sustaining a laceration to the area in a boating accident. Three courses of oral antibiotics failed to slow progression of the lesion. During antibiotic therapy, new papules and plaques arose over the patient’s lower body. A course of oral prednisone was then prescribed. The lesions improved over the course of 1 year with continued prednisone therapy. The patient had two episodes of diverticulitis necessitating left hemicolectomy, during which time his prednisone was stopped. Within days of discontinuing prednisone, however, the patient noted a recurrence of painful, edematous, indurated papules and plaques over both lower extremities. Subsequent biopsy showed a neutrophilic infiltration of the upper dermis without evidence of leukocytoclastic vasculitis or infection.

Over the course of the following 14 years, the patient continued to have frequent, often severe recurrences of similar painful, erythematous, indurated papules, plaques, and vesicles. Maintenance therapy with dapsone and infliximab failed to control his disease. Only high daily doses of oral steroids or sulfasalazine adequately controlled the patient’s symptoms. Despite maintenance dosing, the patient still experiences mild recurrences of his disease. Several subsequent biopsies of the plaques also showed neutrophilic infiltrates in the dermis without vasculitis.

Figure 1	Figure 2
Figure 1. Erythematous plaque of confluent vesicles on the patient’s proximal lower extremity Figure 2. Erythematous confluent vesicles on the distal left lower extremity

Figure 3
Figure 3. Histopathology of lower extremity plaque showing papillary dermal edema and a dense, diffuse dermal infiltrate of primarily neutrophils (H&E, x200)

The patient was referred to our clinic for alternative therapeutic options after laboratory work-up revealed elevated liver function tests secondary to sulfasalazine. When the patient’s sulfasalazine therapy was stopped, a diffuse eruption of papules, nodules, plaques, and pseudo-vesicles erupted within a few days over his legs (Figures 1 and 2), chest, and abdomen. Two 4 mm punch biopsies of two of the lesions were obtained, which showed neutrophilic infiltrates in the dermis consistent with Sweet syndrome.

The patient’s medical history is otherwise not significant for any systemic diseases, including endocrinopathy, malignancy, inflammatory, or autoimmune disorders.

Histopathology

Routine H&E staining reveals a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis (Figure 3).

Laboratory analysis

Laboratory studies were within normal limits, including complete blood count, liver function tests, and all rheumatologic studies including evaluation for paraproteinemia.

Discussion

Since its first description as an acute, febrile, neutrophilic dermatosis, [1] the understanding of Sweet syndrome has evolved greatly. It is now thought to encompass a wide spectrum of disease presentations with many associated etiologies. The onset can be acute with abrupt resolution of cutaneous symptoms upon treatment [2, 3] or the disease can have a chronic, recurrent course [4].

In addition to the skin, aseptic neutrophilic infiltration of organs other than the skin has been described in association with cutaneous lesions. Affected organs include the lungs [5, 6], eye [7], and central nervous system [8] in addition to the skin.

Episodes of aseptic neutrophilic infiltration of the dermis most often occur in reaction to a medication or systemic illness, such as infection, inflammatory bowel disease, autoimmune disorder, paraproteinemia, internal malignancy [9], or pregnancy [10]. An underlying cause can be found in approximately one in five cases [11]. In light of the association with various etiologies and a predilection for women, it has been suggested that Sweet syndrome represents a hypersensitivity reaction [9].

Several variants of chronic, recurrent Sweet syndrome have been previously reported. Christensen reported 2 cases of patients with recurrent annular erythematous, edematous plaques. The histopathology of the lesions was consistent with Sweet syndrome, but the patients presented without fever or general symptoms [12]. Because of the annular lesions and the lack of constitutional symptoms, the authors considered this presentation to be an entity to itself rather than a variant of Sweet. The patients had a chronic, recurrent course with no evidence of systemic disease lasting up to 2 years.

Chronic disease can be associated with an afebrile onset without peripheral leukocytosis or neutrophilia. Cabanillas reported on a patient with a 6-month history of generalized painful erythematous, edematous plaques [11]. The patient did not present with fever or leukocytosis, although he did have neutrophilia and an elevated erythrocyte sedimentation rate. The patient improved after a course of oral prednisone and had only occasional, mild recurrences. The authors considered their case to be more like Christensen chronic, recurrent annular neutrophilic dermatosis, rather than a variant of Sweet syndrome.

Romero reported a series of 4 cases with an afebrile, recurrent course lasting several years [13]. The skin lesions of all 4 patients were consistent with Sweet syndrome by clinical or histological examination. None of the patients had leukocytosis or neutrophilia at any time. Unlike Christensen and Cabanillas, the authors regarded this presentation as a variant of Sweet syndrome.

There are several hereditary disorders, which feature neutrophilic dermatoses as a component, including chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome) and Majeed syndrome. CANDLE syndrome presents with chronic, afebrile neutrophilic dermatosis in concert with lipodystrophy and elevated temperature [14]. The autoinflammatory Majeed syndrome, described in 2 consanguineous Arab families, consists of chronic neutrophilic dermatoses along with chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia [15].

Our patient’s case most closely resembles those reported previously by Romero. On clinical and histological examination, the patient’s skin lesions were consistent with Sweet syndrome. No family history of similar conditions has been reported. Additionally, the patient undergoes regular physical and health maintenance examinations and no underlying illness has been found to correlate with his skin disease.

During the course of his disease, our patient never fulfilled clinical criteria sufficient for a definitive diagnosis of Sweet syndrome, initially proposed by Su and Liu [16] and revised by von den Driesch [17]. Although the major criteria were satisfied during his disease flare-ups, none of the three minor criteria was ever satisfied.

Our case is unique because of the extremely long duration of his disease. The patient has had recurrent disease for over 15 years despite chronic use of anti-inflammatory medications including oral steroids and non-steroidal anti-inflammatory drugs. In addition to the long disease course, our patient’s lesions are also atypically distributed. Sweet syndrome classically affects the face, neck, and upper extremities. Our patient’s lesions showed a predilection for his trunk and lower extremities.

Conclusions

Sweet syndrome was first reported as an acute, febrile neutrophilic dermatosis. It has since been broadened to include diseases acute or chronic, febrile or afebrile, singular or recurrent, sporadic or familial. We report a patient with a 15-year course of afebrile, recurrent neutrophilic dermatosis without peripheral leukocytosis or evidence of underlying systemic illness. Rather than a syndrome, we believe that Sweet is a reaction pattern that may be diagnosed histologically and for which a work-up should follow. Perhaps, like with Raynaud disease and phenomenon, the appropriate terminology should indicate whether the reaction pattern is a primary or secondary process, Sweet disease vs. Sweet phenomenon.

References

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