A 30-year-old male presents to your office with the following findings. He has always had severe acne and gets draining boils on his back, scalp, armpits, groin and buttocks.
What gene is implicated in this condition?
A. Fillagrin
B. PTEN
C. MEVF
D. PSTPIP1
Rationale: The first photograph demonstrates numerous open comedones, cysts, and inflammatory nodules consistent with acne conglobata. The second shows a exudative ulcer with an inflammatory rim and undermined border consistent with pyoderma gangrenosum. The history of boils on the scalp, groin, and buttocks is suggestive of hidradenitis suppurativa. The combination of pyoderma gangrenosum, acne conglobata, and hidradenitis suppurativa is seen in PASH syndrome. Treatment is often difficult - TNFinhibitors, IL-1 inhibitors, combination antibiotic regimens, and immunosuppressive agents have all been used with varying efficacy.
Correct answer: PSTPIP1
Although the pathogenesis of PASH syndrome is not well understood, elevated levels of IL-1 and TNF in skin samples from affected tissue have been found. Mutations in PSTPIP1 have been reported in PASH syndrome as well as mutations in NCSTN. PSTPIP1 stands for protein serine–threonine phosphatase interacting protein and mutations in this gene can lead to elevated IL-1B levels.
Incorrect answers:
A. Fillagrin mutations are seen in atopic dermatitis and ichthyosis vulgaris.
B. PTEN mutations are seen in several syndromes including Cowden syndrome (trichilemmomas, sclerotic fibromas, papilloma, punctate palmoplantar keratoses, ocular findings, and increased risk of breast and thyroid cancers).
C. MEVF mutations are seen in Familial Mediterranean fever syndrome. This syndrome is characterized by repeated episodes of fever, serositis (commonly presenting as abdominal pain), arthritis, and erysipelas-like rashes. Various other cutaneous features have been described such as purpura, subcutaneous nodules, and scrotal swelling.
Additional reading at Fitzpatrick's Dermatology Chapter 80: Acne Variants and Acneiform Eruptions