PA-PASH syndromeM02.30

So far, several clinically distinct syndromes belonging to the group of autoinflammatory syndromes have been described in the literature:

• PAPA: Pyoderma gangraenosum, acne and pyogenic arthritis.
• PASH: Pyoderma gangraenosum, acne and hidradenitis suppurativa
• PASS: Pyoderma gangraenosum, acne, and spondyloarthritis
• PA-PASH: pyoderma gangraenosum, acne, pyogenic arthritis, and hidradenitis suppurativa
• PsA-PASH: psoriatic arthritis, pyoderma gangraenosum, acne and hidradenitis suppurativa
• PAC: Pyoderma gangraenosum, acne and ulcerative colitis

Furthermore, this group of diseases includes the SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis), which is a superordinate umbrella syndrome for a group of other autoinflammatory entities. It is important to raise awareness of the group of autoinflammatory diseases in order to optimize disease management and ultimately improve patients' quality of life.

Autoinflammatory syndromes associated with hidradenitis suppurativa (HS) and/or acne and/or pyogenic arthritis are rare inflammatory disorders with a common pathogenesis involving a dysregulated innate immune system with abnormal interleukin (IL)-1 signaling leading to sterile neutrophilic inflammation in various organs. The clinical features are recurrent fevers, painful arthritis, and neutrophilic dermatoses (hidradenitis suppurativa, acne, and pyoderma gangraenosum). They are accompanied by elevated systemic inflammatory markers in the blood.

Signs of acute or chronic inflammation. Positivity for antineutrophil cytoplasmic autoantibodies(ANCA), MPO-ANCA, and anticardiolipin antibodies is possible (Kawanishi K et al. 2021).

The rarity of these syndromes makes it difficult to establish evidence-based treatment guidelines. In addition, treatment can be challenging due to lack of response to standard treatment modalities.

Both pyoderma gangraenosum and hidradenitis suppurativa belong to the spectrum of neutrophilic dermatoses and are considered autoinflammatory syndromes. They share similar mechanisms from a pathophysiologic perspective, including neutrophil-rich cutaneous inflammation and overexpression of the interleukin-1 (IL-1) family.

A 44-year-old African American man with a history of pyogenic arthritis, acne, purulent hidradenitis, and chronic diarrhea presented for evaluation of painful ulcers on both lower extremities, both proximal interphalangeal joints, buttocks, and scrotum, and chronic diarrhea. Infectious causes for the ulcers were excluded. Biopsy confirmed pyoderma gangraenosum. Colonoscopy revealed ulcerative colitis. After treatment with prednisone, the ulcers healed within 4 weeks, and chronic diarrhea disappeared (Ursani MA et al. 2016).

A 26-year-old man presented with recurrent aseptic pyogenic arthritis, acne, hidradenitis suppurativa, and pyoderma gangraenosum. An endoscopy of the lower gastrointestinal tract was performed and ulcerative colitis was diagnosed. No PSTPIP1 gene mutation was found in the gene sequencing test (Kawanishi K et al. 2021).

1. Antón-Vázquez V et al (2020) Adult-Onset Autoinflammatory Syndromes. J Clin Rheumatol 26: 160-163.
2. Gottlieb J et al. (2019) PAPASH, PsAPASH and PASS autoinflammatory syndromes: phenotypic heterogeneity, common biological signature and response to immunosuppressive regimens. Br J Dermatol 181:866-869.
3. Huang J et al (2022) Pyoderma gangrenosum, acne, and hidradenitis suppurativa syndrome: A case report and literature review. Front Med (Lausanne) 9:856786.
4. Kawanishi K et al. (2021) A case of myeloperoxidase-antineutrophil cytoplasmic antibody and anticardiolipin antibody-positive pyogenic arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa (PAPASH) syndrome with colitis. Mod Rheumatol Case Rep 5: 333-336.
5. Leuenberger M et al (2016) PASS Syndrome: An IL-1-Driven Autoinflammatory Disease. Dermatology 232:254-258.
6. Li M et al. (2022) Secukinumab for PASS syndrome: A new choice for therapeutic challenge? Dermatol Ther 35:e15507.
7. Schwob E et al (2020) PASS: a rare syndrome within the autoinflammatory diseases that still lacks a genetic marker. J Eur Acad Dermatol Venereol 34:e478-e480.
8. Ursani MA et al (2016) Pyogenic arthritis, pyoderma gangrenosum, acne, suppurative hidradenitis (PA-PASH) syndrome: An Atypical Presentation of a Rare Syndrome. Am J Case Rep 17:587-591.
9. Vinkel C et al (2017) Autoinflammatory syndromes associated with hidradenitis suppurativa and/or acne. Int J Dermatol 56:811-818.