Dear Editor, Amicrobial pustulosis of the folds (APF) is a rare neutrophilic dermatosis, classically associated with autoimmune diseases, especially systemic lupus erythematosus.1 With increasing usage of immunobiological agents, there are a few reports of its paradoxical induction with tumor necrosis factor inhibitors (anti-TNF), particularly in patients with inflammatory bowel disease.2-5 A 68-year-old man presented with recurrent pustular lesions on the armpits and trunk for 5 years. He had a history of severe stenosing Crohn’s disease and had been treated with adalimumab for 7 years, currently without any signs of active disease. He had been unsuccessfully treated with topical steroids, antibiotics, and antifungals. On examination, macerated erythematous plaques on the armpits with pustules were presented Figure 1. Follicular and nonfollicular pustules with an erythematous base were distributed mainly on the trunk and less so on the limbs Figure 2a. He reported previously having similar groin and intergluteal cleft lesions. There were no systemic symptoms, and the laboratory profile was unremarkable, including a negative antinuclear antibody. Skin biopsy revealed a subcorneal neutrophilic pustule, spongiosis, and lymphoplasmacytic inflammatory infiltrate with sparse neutrophils in the superficial dermis Figures 3 and 4. Fungal, bacterial, and mycobacterial cultures were negative. A diagnosis of APF induced by adalimumab was established. Treatment with dapsone (50 mg/day) was instituted, without recurrences throughout the 6-month follow-up Figure 2b.Figure 1: Macerated erythematous plaques with pustules on the axillaFigure 2: (a) Follicular and nonfollicular pustules with an erythematous base on the trunk; (b) Thirty days after starting dapsoneFigure 3: Subcorneal neutrophilic pustule, spongiosis, and lymphoplasmacytic inflammatory infiltrate with scattered neutrophils in the superficial dermis (H and E, ×40)Figure 4: Subcorneal neutrophilic pustule (H and E, ×100)Paradoxical skin reactions (PSRs) with immunobiological drugs are induction or condition exacerbation that usually responds to this drug class while treating another disease. The most common PSRs described with anti-TNF agents are psoriasiform reactions, with neutrophilic dermatosis being rarely reported.5 Mechanisms may involve imbalance in cytokines, a modified skin immune response with increased migration of innate or adaptive activated immune cells to the skin, dysfunction of regulatory T cells, and an uncontrolled increase of interferon alpha due to TNF pathway blockade.5 Other frequent diagnoses should be investigated, such as pustular psoriasis, as it is a commonly reported cutaneous adverse reaction associated with anti-TNF medications.1,2 It typically presents as localized pustulosis of the palms and soles, but can appear as guttate, plaque, or nail psoriasis. Alternative diagnosis include acute generalized exanthematous pustulosis, subcorneal pustulosis, and pustular pyoderma gangrenosum.1,2 As patients undergoing treatment with anti-TNF are more susceptible to infectious dermatoses, bacterial and fungal folliculitis should be ruled out with microbiological culture samples.1,5 An anatomopathological exam can be performed, and its typical findings include spongiform pustules and dermal edema with neutrophilic and lymphocytic inflammatory infiltrate, although some differential diagnosis can have similar findings, such as pustular psoriasis and the few related monogenic inflammatory diseases, such as deficiency of interleukin-36 receptor antagonist.1,4 The current therapeutic approach to APF is systemic steroids, 0,5 mg/kg/day of prednisone, with gradual reduction.1 The topical form can also be used.4 Dapsone has good response rates, with or without systemic steroids.1,4 Other treatments include colchicine, cyclosporine, Ustekinumab, and anti-TNF agents, although the latter can cause APF as a paradoxical reaction.1,4 In paradoxical anti-TNF cases, especially in nonresponders to treatment, discontinuing the drug can be beneficial.2,3 We hereby present a rare case of APF with typical clinical and histopathological features, drawing attention to knowledge about uncommon paradoxical reactions to anti-TNF agents. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Sanseverino et al. (Thu,) studied this question.