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Chronic annular pustular psoriasis resembling subcorneal pustular dermatosis: A case report

Generalized pustular psoriasis and subcorneal pustular dermatosis are generalized pustular dermatoses that are characterized by the subcorneal accumulation of neutrophils. Careful examination is important in distinguishing these diseases for appropriate management. Patients with acute generalized pustular psoriasis are systemically unwell with discrete pustules as opposed to the chronicity and associated hypopyon lesions in subcorneal pustular dermatosis. Generalized pustular psoriasis lesions demonstrate psoriasiform changes on histology and the increased expression of Th17 cytokines. We describe a middle-aged woman presenting with chronic annular generalized pustular psoriasis, initially mistaken for subcorneal pustular dermatosis due to their clinical and histological semblance. The patient had recurrent skin disease for 6 years despite conventional therapy of oral retinoid, immunosuppressant and biologic therapy. Complete and persistent clearance of her skin lesions was achieved with secukinumab, an interleukin 17A inhibitor.


Introduction
The differentiation of SPD (subcorneal pustular dermatosis or Sneddon-Wilkinson disease) and generalized pustular psoriasis (GPP) poses a diagnostic challenge as they present similarly both clinically and histologically. They are relaps ing neutrophilic dermatoses characterized by widespread symmetrical crops of sterile pustules over an erythematous base that arise predominantly over the trunk and flexural aspects of limbs. 1,2 GPP is further subtyped into acute (von Zumbusch) and subacute annular variants. The presenting morphology of both SPD and annular GPP is similar where the pustules coalesce to form annular or serpiginous pat terns. 2 In addition, histological changes in both SPD and GPP include subcorneal pustules filled with neutrophils and occasional eosinophils sitting on top of the epidermis. The upper dermis also shows perivascular and interstitial infiltra tion of neutrophils and occasional monocytes and eosino phils. 3 Commonly, with appropriate treatment, the pustules of both SPD and GPP resolve completely within several days. However, relapse of skin disease is a characteristic fea ture of both SPD and GPP.
This case highlights the diagnostic challenges in diffe rentiating between GPP and SPD. We document a unique presentation of annular GPP that was initially mistaken for SPD and treated with a multiple drugs. Recognizing key fea tures and differences between the two skin conditions are important in understanding their longterm disease course and management.

Case report
A woman in her 50s with a 3year history of pustular derma tosis was referred for assessment of a 1month history of extensive flare of eruption to the back, arms and legs. The patient complained of lowgrade fever, pruritus and skin pain. She had lost 8 lbs unintentionally over the prior month. Three years prior, she was diagnosed with SPD on the basis Chronic annular pustular psoriasis resembling subcorneal pustular dermatosis: A case report of skin biopsy and clinical presentation. She had been started on dapsone, 50 mg daily, and clobetasol propionate oint ment, 1 year prior to our assessment with minimal improve ment. Additional medication use included betamethasone valerate cream, 0.01% twice daily; citalopram, 50 mg daily; hydroxyzine, 10 mg three times daily; lorazepam, 1 mg as needed; and nasal mometasone furoate, daily.
On examination, she presented with a generalized polyannu lar and polycyclic pustular and papular eruption with trailing scale and erythema affecting 50% of her body -including the trunk and limbs but sparing the face (Figure 1). A repeat biopsy of the right flank showed spongiosis with parakeratosis, several intracorneal and subcorneal pustules (Figure 2(a)), negative direct immunofluorescence and normal serum protein electrophoresis.
These tests ruled out SPD type IgA pemphigus and monoclonal gammopathyassociated disease. The psoriasiform histology and the clinical presentation were consistent with annular GPP.
The patient was started on a tapering regimen of pred nisone, 40 mg every morning for 1 week followed by 20 mg every morning for 1 week and then 10 mg every morning for 1 week. The dose of dapsone was increased to 100 mg, daily. Over the course of 6 years, the patient continued to have per sistent eruptions consisting of annular pustules with erythe matous macules over the trunk and extremities with recurrent flares and systemic illness that required hospitalization on one occasion. Her chronic annular GPP demonstrated mini mal improvement with acitretin, cyclosporine, infliximab and ustekinumab. Concurrent hepatitis C was viewed as a  relative contraindication to therapy with methotrexate. Immunohistochemical analysis of lesional skin demonstrated interleukin (IL)17A expression by the epidermis and dermal lymphocytes (Figure 2(b)). Treatment with secukinumab was initiated with complete and sustained clearance of skin disease over 2 years of continued therapy (300 mg/month).

Discussion
This case serves to document the nosological confusion sur rounding the diagnosis of GPP and SPD, due to their clinical and histological semblance. Demographically, the subacute annular variant of GPP has been described mostly in children, whereas both acute GPP and SPD occur more commonly in adults between the ages of 40 and 60 years. 2,4,5 Clinically, GPP initially develops as painful erythematous papules and pus tules, accompanied by fever, rigors and malaise. Patients often appear systemically ill, and lifethreatening complications can occur without supportive treatment. 1 In contrast, SPD has a benign and chronic clinical course. In addition, the pustules in SPD arise as half pustular, half vesicular blisters, as opposed to purely pinpoint pustules commonly seen in GPP. 2 Histologically, the hallmark differences between GPP and SPD include the classic psoriasiform changes seen in the epidermis of patients with GPP, parakeratosis, elongation of rete ridges spongiform pustules of Kogoj and acantholysis. 2,6 However, biopsy of older pustules in GPP can be histologically identical to SPD, which lack spongiform changes from epidermal healing.
Firstline treatments for SPD and GPP are oral dapsone and acitretin, respectively. However, relapses are common and patients are directed towards secondline therapies, which include antineutrophilic, topical or oral steroids, psoralen plus ultraviolet light (PUVA) and newer biologic therapies. 2,7 No randomized trials have addressed the efficacy of therapy for SPD or GPP. Recently, case series have documented the effi cacy of anti-tumour necrosis factor α (TNFα) and antiIL12/23 agents in the resolution of skin disease in both SPD and GPP. 2,7 Like TNFα, IL17A, a proinflammatory cytokine, plays an important role in the recruitment of neutrophils to the epidermis of patients with psoriasis. The pathogenesis of GPP is postulated to involve the interaction between the adaptive immune system through the IL17/23 axis with the keratinocytederived IL36 pathway of the innate immune system. A recent study has demon strated the potential role of IL36 in inducing the IL17A pathway either directly or indirectly via IL23 expression and that it may act concertedly with IL17A in the exacerbation of inflammation in pustular psoriasis. 8 Secukinumab, an IL17A monoclonal anti body, is approved for the treatment of plaque psoriasis. The effi cacy of secukinumab for acute GPP has recently been documented in a 52week openlabel study, as well as in case reports. 9,10 The efficacy of secukinumab on SPD or annular GPP has yet to be reported. Although our patient's clinical presentation and histo logic findings were similar to that of SPD, the lack of remission to the initial therapeutic regiments, concomitant psoriasiform epi dermal hyperplasia on skin biopsy, and the chronic course of pus tulation and erythema with recurrent flares of systemic illness suggest an unusual presentation of chronic annular GPP.
This case highlights the importance of recognizing the subtle clinical and histological differences between SPD and annular GPP. The proinflammatory cytokine, IL17A, pos sibly in synergy with IL36, plays an important role in the pathogenesis of GPP. Recognition of annular GPP can lead to the initiation of secukinumab, or other IL17 inhibitors, for complete and sustained clearance of skin disease.

Authors' Note
In the past 2 years, Dr Dutz has been a member of advisory boards and a speaker for Janssen, Abbvie, Amgen, Leo Pharma, Celgene, Lilly, Bausch Health, Sanofi Genzyme and Novartis and has par ticipated in clinical trials supported by Janssen, Abbvie and Novartis.

Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, author ship, and/or publication of this article.

Informed consent
A written informed consent was obtained from the patient.