Pyrin-associated autoinflammation with neutrophilic dermatosis
First described in a family of Belgian ancestry spanning 3 generations, PAAND has since been identified in 6 additional families / individuals of Spanish, Japanese, and Iranian-Azeri ancestry, and from the United Kingdom, France, and Lebanon. As a rare disease, the populations affected by PAAND are still being characterized, but current studies have shown equal distributions between sexes, with the majority of disease onset during childhood, although a few cases of adult onset have been noted. The predominant mode of inheritance is autosomal dominant with incomplete penetrance, but one study identified an autosomal recessive mode of inheritance as well in a family of first-cousin consanguineous parents.
PAAND most commonly presents with recurrent neutrophilic dermatoses (severe acne, sterile skin abscesses, pyoderma gangrenosum, hidradenitis suppurativa, and cutaneous neutrophilic small-vessel vasculitis) and periodic fevers that last several weeks. Some patients experience a distinct exanthematous and pustular eruption that can be widespread or limited to the perioral region, upper and lower extremities, and perineal mucosa. Cutaneous eruptions are often the first manifestations of PAAND and can often persist or undergo a cyclical pattern. Patients will often have multiple cutaneous manifestations, with almost all patients experiencing acne, folliculitis, and pyoderma gangrenosum. Other common manifestations include arthralgia; myalgia / myositis; oligoarthritis / polyarthritis; abdominal pain accompanied by diarrhea, nausea, and vomiting; gastrointestinal (GI) inflammation; and anemia. Developmental delay is seen in patients with childhood onset. Rare manifestations include reported occurrence of dilated cardiomyopathy in a patient aged 13 years that evolved into chronic cardiac decompensation necessitating cardiac transplantation at age 20. Symptoms usually increase in severity with age.
M04.8 – Other autoinflammatory syndromes
724834006 – Neutrophilic dermatosis
Differential Diagnosis & Pitfalls
- Familial Mediterranean fever (FMF) – also due to MEFV gene mutations, autosomal recessive inheritance and presents with recurrent febrile episodes lasting less than 3 days with serositis and amyloidosis. Recurrent erysipelas-like erythema affecting the lower extremities is the most frequent cutaneous manifestation.
- Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA)
- Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)
- Pyogenic arthritis and PASH (PAPASH)
- Pyoderma gangrenosum, acne, and spondyloarthropathies (PASS)
- Sweet syndrome
- Cryopyrin-associated autoinflammatory syndromes (CAPS)
- Systemic lupus erythematosus
- Behçet disease
- Henoch-Schönlein purpura
- Erythema nodosum
- Juvenile inflammatory arthritis
- Ankylosing spondylitis
- Inflammatory bowel disease