, , hidradenitis suppurativa and arthralgia: PASH or PAPA syndrome?

uto inflammatory diseases (AIDs) are a group of disorders family members presented with similar manifestations. Patient characterized by the dysregulation of innate immune applied herbal liniment and self medicated with amoxicillin system and the absence of circulating autoantibodies 500 mg/tab one tablet thrice a day with no relief. She was also A 1 and autoreactive T-cells. The AIDs characterized by seen by several physicians, given oral and topical antibiotics neutrophilic dermatoses includes PAPA (pyogenic , that didn’t seem to seem to improve her condition. pyoderma gangrenosum (PG) and acne), PASH (PG, acne and Examination revealed multiple erythematous papules, hidradenitis suppurativa), PAPASH (pyogenic arthritis, acne, PG plaques, nodules, pustules, with open and closed comedones and hidradenitis suppurativa), PASS (pyoderma gangrenosum, on the face (Figure 1A); hyperpigmented nodules and ulcers acne and sterile spondyloarthritis), PsAPASH (, on the buttocks and posterior thigh (Figure 1B); erythematous, PG, acne, and hidradenitis suppurativa) and PAC (PG, acne, and nodules and ulcers with rolled violaceous borders topped ulcerative colitis).1,2 with thick yellow crusts located on the shoulders, upper and PASH syndrome is an autoinflammatory syndrome lower extremities (Figure 2A). Pathergy test was done on the distinct from PAPA syndrome due to lack of intensive joint volar surface of the right forearm, which revealed a pustular inflammation.3 At present, there have been only 14 cases formation on the site after 48 hours. reported worldwide.1 According to the Philippine Dermatologic Hematologic test showed elevated white blood cell Society (PDS) central registry from 2011-2016, this is the only of 17.55 x 109/uL (normal: 5-10 x 109/uL), predominantly recorded case of PASH syndrome.4 neutrophilia at 82%. Erythrocyte sedimentation rate and As a dermatologist, it is important that we be able c-reactive protein were also elevated. The hepatic and renal to distinguish between the different auto inflammatory function test were within normal limits. Urinalysis and chest syndromes. Early diagnosis and management of these radiograph were unremarkable. Blood and wound cultures patients can prevent morbidity and improve the quality of and KOH showed no growth. Purified protein derivative (PPD) life of patients. We report a rare case of PASH syndrome who tests done on 48th and 72nd hour was also negative. Antinuclear dramatically improved with oral corticosteroids and dapsone. antibody (ANA) was negative. We present a case of a 20-year-old woman of Filipino Histopathology revealed dense inflammatory infiltrates descent born in a non-consanguineous parents with a three- containing predominantly neutrophils in the dermis and month history of non-healing crusted ulcers. It started as subcutaneous layer, which was consistent of neutrophilic a solitary pustule located at the right arm that progressed dermatosis (Figure 3). to a plaque, which eventually ulcerated. It was noted to be Among the different auto inflammatory syndromes, pruritic and tender. It was associated with fever and symmetric the closest differential was PAPA syndrome. Since we could polyarthralgia involving the wrists, elbows and ankles. No other not establish the presence of pyogenic sterile arthritis, we

A B

Figure 1. (A) Multiple, erythematous to hyperpigmented papules, plaques, nodules, pustules, with open and closed comedones on the face and (B) multiple hyperpigmented nodules and ulcers on the posterior thigh. A B

Figure 2. (A) Erythematous ulcers with rolled violaceous borders topped with Figure 3. (A) Skin punch biopsy taken from the on the right shoulder. The thick yellow crusts and (B) after six months of treatment there was marked dermis and subcutaneous contain dense inflammatory infiltrates containing improvement in the lesion. numerous neutrophils (hematoxylin-eosin stain, 10x) and (B) multiple neutrophils located at the dermis (hematoxylin-eosin stain, 40x) managed the patient as a case of PASH syndrome. binding affinity to pyrin therefore causing overproduction of Patient was started with prednisone at 20 mg/day (0.5 IL-1ß. There will be uncontrolled release of pro-inflammatory mg/kg/day) which was the lowest effective dose, for five cytokines such as IL-17, causing recruitment and activation of months and it was gradually tapered. In addition, benzoyl neutrophils.6 The diagnosis of PASH syndrome is based on its peroxide 5% gel, adapalene 0.1% gel and doxycycline 200 mg/ clinical features. Similar findings with PAPA syndrome, includes day for four months which showed resolution of acne lesions. biopsy result showing neutrophilic infiltration and negative There was improvement in the ulcers however joint pains wound cultures.1 persisted. Dapsone 50 mg/day was added after five months Corticosteroid may play an important role in the the of prednisone as steroid-sparer, after a normal G6PD test. The early treatment of AIDs.7 However, if treatment with a single dosage of dapsone was slowly increased to 200 mg daily while agent is unsuccessful, another treatment option is to use tapering prednisone at 5 mg daily for 1 month (Figure 2B). The combination treatment with TNF inhibitors and dapsone and/ skin and joint manifestations showed significant improvement or cyclosporine.8 Other managements of PASH syndrome after 6 months of treatment, with no recurrence after 1 year includes the combination of surgery and antibiotic therapy.9 of follow-up. Ideally, this case would be more interesting if we were PASH syndrome was first reported in 2012 and it was able to perform a gene mutation study since PASH syndrome differentiated from PAPA syndrome because of the absence can also present with a heterozygous missense mutation in of pyogenic arthrtitis and absence of mutation in the PSTPIP1 the PSTPIP1 gene, same with PAPA syndrome. gene. However, recently there was 1 reported case of PASH In conclusion, we present a rare case of PASH syndrome, that has a PSTPIP1 gene mutation.5 that presented with the typical clinical triad. We successfully Mutation on the PSTPIP1 gene leads to the increased treatedA the patient with prednisoneB and dapsone.

Janice Natasha C. Ng, MD Lalaine R. Visitacion, MD, FPDS Mary Jo Kristine S. Bunagan, MD, FPDS Department of Dermatology, Southern Philippines Medical Center, Davao City E-mail: [email protected]

REFERENCES

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