Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterised by painful progressive skin ulceration. Medical management with corticosteroids and other immunomodulatory agents remains the mainstay of treatment. Surgical intervention has traditionally been avoided because of the risk of pathergy, whereby minor trauma progresses to ulceration. However, extensive or limb-threatening defects may necessitate reconstruction. We present a case of PG affecting the dorsum of the foot requiring free tissue transfer.

To summarize and critically evaluate recent literature on autoinflammatory syndromes of hidradenitis suppurativa (HS).

Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant hereditary autoinflammatory disease caused by PSTPIP1 gene variants and belongs to the PSTPIP1-associated inflammatory diseases (PAIDs). Its core clinical manifestations include recurrent pyogenic arthritis, pyoderma gangrenosum, and severe acne with onset in childhood or adolescence. Some patients may also present with multisystem involvement, such as inflammatory bowel disease and scleritis. Inflammation markers, such as CRP and ESR, are often significantly elevated. Treatment mainly involves targeted inhibition of inflammatory pathways, such as IL-1 inhibitors and TNF-α inhibitors. In this article, we report a Chinese patient with PAPA syndrome with disease onset at 13 years of age, whose main manifestations were pyoderma gangrenosum and acne. Genetic testing revealed a de novo PSTPIP1 gene variant (c.748G>A, p.Glu250Lys). We also reviewed recent literature on PAPA syndrome, summarizing its clinical manifestations, diagnosis, and treatment to enhance physicians' understanding of the condition.

The pathogenic mechanisms underlying pyoderma gangrenosum (PG) remain unclear. Here we report three patients with PG from two unrelated kindreds with homozygous R57C mutation of the linear deubiquitinase OTULIN. The patients have isolated, pediatric-onset, OTULIN-related PG (ORP). In contrast to OTULIN-related autoinflammatory syndrome (ORAS), caused by mutations affecting the catalytic domain, R57C affects the PUB-interacting motif with distinct biochemical, immunological and clinical consequences. OTULIN-R57C is catalytically active but is unable to bind the linear ubiquitin assembly complex (LUBAC). Patient monocytes show heightened expression of IL1B, and OTULIN-R57C fails to suppress inflammasome activity. Patients have elevated levels of TNF, and their dermal fibroblasts show heightened susceptibility to TNF-dependent cell death. Homozygosity for OTULIN-R57C leads to accumulation of linear ubiquitin and LUBAC autoubiquitination in patients' dermal fibroblasts, consistent with pathogenic LUBAC activity. These findings identify a genetic etiology of isolated PG of childhood. We propose a multifactorial mechanism of ORP, including myeloid IL-1β production and TNF-driven death of skin-resident cells, suggesting that blockade of IL-1β or TNF are therapeutic options in PG.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis typically associated with autoimmune disease; however, its coexistence with giant cell arteritis (GCA) and optic neuritis is exceedingly uncommon and rarely reported. We describe a woman in her early 70s with rheumatoid arthritis and recently diagnosed GCA who developed painful breast ulcers while on tapering systemic corticosteroids for GCA, shortly after a herpes zoster infection. The ulcers showed classic PG morphology and fulfilled Delphi diagnostic criteria. She had preceding MRI-confirmed bilateral optic neuritis followed by bilateral temporal arteritis. Intralesional corticosteroid therapy resulted in complete ulcer healing within 1 month. This case highlights an unusual constellation of PG, GCA, rheumatoid arthritis and optic neuritis, with herpes zoster as a potential pathergic trigger. It emphasises the importance of considering PG in atypical ulceration occurring in patients with multisystem autoimmunity, even when lesions develop despite ongoing low-dose systemic corticosteroid therapy.

Mutations in the gene PSTPIP1 may cause several different autoinflammatory syndromes, but the mechanisms by which distinct PSTPIP1 mutations lead to these differing phenotypes are not fully understood. The two best characterized autoinflammatory conditions resulting from PSTPIP1 mutation are pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome and PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. Here, we report a novel gain-of-function PSTPIP1 mutation (p.N236K) causing PAMI syndrome in a patient with systemic autoinflammation and severe neutropenia. This mutant form of PSTPIP1 shows increased binding to pyrin and leads to heightened inflammasome formation, relative to WT PSTPIP1. We also identify a transcriptional signature in blood from PAMI patients suggestive of enhanced T cell activation and altered neutrophil survival and/or function. Further research on PSTPIP1-related autoinflammatory conditions is needed to more deeply understand the genetic and immunological drivers of disease and contribute to improving patient outcomes.

We present the case of a 60-year-old man with granulomatosis with polyangiitis (GPA). While he initially presented with only renal involvement, he developed cutaneous manifestations more than a decade later. Cutaneous manifestations may manifest at any point during the duration of the disease, although most usually present at the onset. Cutaneous manifestations of GPA include petechial-like lesions and palpable purpura, typical of what is seen with small vessel vasculitides, as well as pyoderma gangrenosum (PG)-like lesions, digital necrosis, subcutaneous nodules, and/or livedo, which can also be seen but may be more commonly associated with medium vasculitis. As these manifestations may also be found in tandem with other diseases, it is important to include GPA as part of the differential diagnosis when such skin lesions are identified. Treatment of cutaneous manifestations of GPA includes glucocorticoids and immunosuppressive agents.