Bullous subtype of rheumatoid neutrophilic dermatosis - An uncommon variant of a rare disease

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Neutrophilic dermatoses (ND) encompass a spectrum of inflammatory conditions characterised by a neutrophilic infiltrate on histopathological examination. The cutaneous manifestations of ND demonstrate considerable diversity, with various clinical presentations, sometimes observed even in the same patient.¹ The localisation of the neutrophilic infiltrate (epidermal, dermal, and/or subcutaneous), clinical presentation, and disease duration collectively contribute to the differentiation of each ND.² ND are commonly associated with infectious, inflammatory and neoplastic disorders as well as with certain medications.³

Rheumatoid neutrophilic dermatosis (RND) is a rare inflammatory skin condition. Similarly to the other ND, RND is characterised by a neutrophilic sterile dermal infiltrate on histopathological examination.⁴ The precise aetiology of RND remains poorly understood. However, the involvement of circulating immune complexes, the release of chemotactic cytokines, cytokine imbalance, and neutrophil migration contributes to the pathogenesis of this disorder.⁵ RND is typically located on the extensor surfaces of the extremities as small painless papules, nodules, or plaques in individuals with long-term rheumatoid arthritis (RA) or its exacerbation. Blisters, pustules, and involvement of the neck and trunk are uncommon manifestations of RND.⁶

Bullous form of RND is an extremely rare condition with only a few reported cases in the literature. Clinically, it can present similarly to bullous pemphigoid. The results of further workup, including direct immunofluorescence (DIF) of skin biopsy sample, histopathology, and circulating basement membrane zone autoantibodies, are usually sufficient to differentiate among these entities [Table 1]. In most cases, the lesions are seen on the lower legs, commonly in female patients with severe RA, although patients with different distributions of cutaneous findings have been reported, such as involvement of palms and soles.⁶ Treatment typically includes medications aimed at managing RA exacerbation or dapsone. A bullous subtype of RND appears to be resistant to systemic steroids, which necessitates a preference for alternative treatment approaches.⁷

A 61-year-old man with a diagnosis of seropositive RA was admitted to the dermatology department for the assessment and management of cutaneous lesions. The patient reported the onset of firm papules in the left elbow region five months prior to admission, followed by the development of plaques with tense blisters at the periphery of the lesions. These lesions subsequently became widespread. Upon admission, the patient exhibited erythematous ring-shaped plaques with small vesicles and bullae arranged in a festoon-like manner in the upper extremities, trunk, and lower extremities, along with violet papular lesions on the elbows, knees, umbilical area, and thighs [Figure 1a-c].

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Figure 1:

a) Ring-shaped plaques on the back and upper extremities, b) Close-up view of the plaques showing small vesicles and bullae arranged at the periphery of the lesions, c) Close-up view of the lesions on thighs with violet papules.

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Approximately one month before the occurrence of the skin lesions, leflunomide 20 mg/day and methylprednisolone 4 mg/day were initiated to address an exacerbation of RA.

During the hospitalisation, the patient presented with only skin lesions.No constitutional symptoms (fever, malaise, pain,) were observed. The laboratory anti-Dsg and anti-BMZ antibodies revealed slightly elevated bilirubin 25 μmol/L (5,1-20,5 μmol/l), γ-glutamyl transpeptidase 528 U/L (<40 IU/l), lactate dehydrogenase 266 U/L (120-240 U/l), total cholesterol 198 mg/dL (<40 IU/l), and increased inflammatory markers (erythrocyte sedimentation rate 47mm (20 mm/h) and C-reactive protein 1.7 μmol/L (<0.5). Additional tests for antinuclear antibodies, anti-Dsg and anti-BMZ antibodies, anti-neutrophil cytoplasmic antibodies, myeloperoxidase, proteinase 3, glomerular basement membrane antibodies, and Borrelia burgdorferi IgM/IgG antibodies were negative. Skin biopsy indicated suppurative dermatitis with diffuse neutrophil infiltration in the superficial and middle dermal layers and superficial erosion, consistent with a diagnosis of RND [Figure 2a-b]. Immunopathological DIF revealed granular deposits of immunoglobulin G in the vessel walls.

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Figure 2a:

Neutrophilic infiltration mainly seen in the dermis, mostly expressed in its upper layers (Haematoxylin & eosin, 40x).

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Figure 2b:

Erosion with a confluent neutrophilic infiltrate at its base (Haematoxyin & eosin, 200x).

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Before histopathology and DIF tests results were available, due to extensive skin involvement, the treatment regimen comprised topical steroids and a pulse of intravenous methylprednisolone (two infusions of 500 mg each), followed by oral methylprednisolone at 4 mg/day and subcutaneous methotrexate at a dose of 15 mg/week. The provided therapy enabled us to achieve complete resolution of the skin lesions after ten weeks. The steroid dose was gradually tapered. Methotrexate treatment was continued for six months before being discontinued, following which the patient was referred to the rheumatology clinic for ongoing RA management.

Bullous RND is a rare dermatological manifestation of RA exacerbation. Clinicians should be knowledgeable about this specific disease presentation and include it in the list of potential differential diagnoses, particularly when evaluating RA patients with bullous skin lesions and negative results from additional diagnostic tests. This case is of particular interest because it describes a case of RND not previously reported, with blisters at the periphery of the lesions arranged in a festoon-like manner, typically reserved for bullous IgA dermatosis.