PASH syndrome is a rare autoinflammatory disorder characterized primarily by pyoderma gangrenosum, acne, and suppurative hidradenitis. It is frequently misdiagnosed or underdiagnosed due to its diverse clinical manifestations. PASH syndrome is considered a polygenic autoinflammatory disease associated with multiple gene variants, among which MEFV variants may play a significant role. This case report describes a PASH syndrome patient with the MEFV variant (NM_000243.3.442G > C; p.Glu148Gln). The E148Q variant appears with high frequency as a homozygote in the gnomAD database, and its pathogenicity remains controversial. This case report describes a Chinese male patient with PASH syndrome who initially presented with severe acne and suppurative hidradenitis that were unresponsive to conventional therapy, subsequently developing pyoderma gangrenosum, leading to the diagnosis of PASH syndrome. Whole-exome sequencing performed during the diagnostic workup revealed the MEFV gene variant (p.E148Q). Treatment with adalimumab ultimately achieved favorable therapeutic outcomes. This case report represents the first documentation of a PASH syndrome patient carrying the homozygous E148Q variant. Adalimumab demonstrated good therapeutic efficacy; however, disease recurrence occurred due to poor medication adherence, highlighting the importance of long-term management. The pathogenicity of E148Q alone is relatively weak and likely depends on polygenic accumulation or epigenetic dysregulation. It may contribute to disease pathogenesis through a "variant load" mechanism in conjunction with ethnic differences and other genetic or environmental factors.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that can be treated with a variety of medical and surgical therapies. However, these therapies carry inherent risks that might be heightened in medically complex patients. This narrative review examines literature for the nuances of standard HS management in immunosuppressed individuals, patients with cancer, and those with gastrointestinal or cardiovascular comorbidities, Down syndrome, and PASH syndrome, a rare condition that is characterized by the presence of pyoderma gangrenosum (PG), acne, and HS. The treatment of HS often requires systemic immunomodulators, and their use necessitates a careful risk-benefit analysis to balance disease control and infection risk in patients who are immunosuppressed. Owing to chronic inflammation, HS is associated with an increased risk of malignancies such as cutaneous squamous cell carcinoma. Vigilant screening and histopathologic evaluation of chronic HS lesions are required for chronic lesions and patients with concurrent cancer. There is a high prevalence of inflammatory bowel disease (IBD) in patients with HS, and this can present unique challenges in management. For example, some biologic therapies commonly used for HS can exacerbate IBD symptoms. Cardiovascular disease is a common comorbidity in HS and demands a multidisciplinary approach to risk assessment and treatment, particularly given the systemic inflammatory burden of HS. Patients with Down syndrome are disproportionately affected by HS and often receive suboptimal treatment, underscoring the need for improved screening and access to therapies. PASH and other related syndromes are rare variants of HS and can be a challenge to manage owing to their unpredictable response to tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) inhibitors. Across these unique populations, surgical intervention continues to be a viable option in refractory cases, even with the risk of impaired wound healing in patients who are immunosuppressed and have cancer. Ultimately, a comprehensive, multidisciplinary approach is essential to optimize HS management in these special populations, integrating surgical and systemic therapies while mitigating associated risks.

PASH syndrome, is autoinflammatory condition driven by immune system dysfunction, resulting in elevated interleukin 1 levels and subsequent production of proinflammatory cytokines and chemokines. The clinical progression of PASH typically starts with acne conglobate in adolescence, followed by hidradenitis suppurativa, and pyoderma gangrenosum. Diagnosis relies on recognizing these hallmark features, but treatment remains a challenge despite current understanding. Conventional immunosuppressive therapies have shown limited efficacy in managing PASH syndrome. The authors present a 36-year-old man with a complex combination of pyoderma gangrenosum, acne, suppurative hidradenitis, obesity, and Crohn's disease. The patient's symptoms began in adolescence with acne and recurrent furuncles, evolving into painful skin ulcers and fistulas over time. Histological examination confirmed the diagnosis of pyoderma gangrenosum. Despite various treatment modalities, including isotretinoin, cyclosporine, azathioprine, and adalimumab, the patient experienced only partial improvement until receiving Infliximab, which led to remarkable improvement. PASH syndrome, a rare neutrophilic dermatosis linked to autoinflammatory conditions like Braun Flaco, is characterized by Pyoderma gangrenosum, acne, and suppurative hidradenitis. This clinical entity presents diagnostic challenges due to its unique features and association with obesity and bowel diseases, such as Crohn's disease. Treatment options, including TNF-α blockers like Infliximab, have shown promising results in controlling cutaneous manifestations. Our case study underscores the complexity of treating PASH syndrome and highlights the importance of personalized therapeutic approaches for optimal outcomes. PASH syndrome presents significant diagnostic and treatment challenges due to its complex symptomatology and associations with conditions like Crohn's disease. The case of a 36-year-old man demonstrates the partial efficacy of conventional therapies and highlights the promising results of infliximab. This underscores the need for personalized treatment strategies and ongoing research to improve outcomes for patients with this rare and intricate syndrome.