PAPA syndrome, also known as Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne syndrome, is a rare autoinflammatory disorder characterized by a triad of symptoms: pyogenic arthritis, pyoderma gangrenosum, and severe acne.
The exact pathophysiology of PAPA syndrome is not yet fully understood. However, it is believed to be an autosomal dominant disorder caused by mutations in the PSTPIP1 gene, which is involved in regulating the immune system and inflammatory responses. The mutations lead to dysregulated production of pro-inflammatory cytokines, primarily interleukin-1 beta (IL-1β), resulting in chronic inflammation and tissue damage.
Clinical and Distinctive Features:
PAPA syndrome typically manifests in childhood or adolescence, although adult-onset cases have also been reported. The clinical features of PAPA syndrome include:
- Pyogenic Arthritis: Recurrent episodes of painful joint inflammation, particularly affecting large joints such as the knees, hips, and ankles. These episodes are characterized by swelling, warmth, and limited range of motion.
- Pyoderma Gangrenosum: Painful skin ulcers that develop in various areas of the body, most commonly on the lower extremities. These ulcers begin as pustules and progress to deep, necrotic wounds with undermined borders.
- Severe Acne: Persistent and severe acne, nodulocystic type, that is resistant to conventional treatments. It often involves the face, chest, and back, and can lead to scarring.
Diagnosing PAPA syndrome can be challenging due to its rarity and overlapping symptoms with other conditions. However, a comprehensive evaluation including a detailed medical history, physical examination, and laboratory tests can aid in the diagnosis. Key diagnostic criteria include the presence of the characteristic triad of symptoms and genetic testing to identify mutations in the PSTPIP1 gene.
The management of PAPA syndrome focuses on controlling symptoms, reducing inflammation, and preventing complications. Also, it involves a variety of approaches depending on the dominant manifestation:
– Arthritis episodes often respond well to oral or intra-articular corticosteroids.
– In cases where corticosteroids are not satisfactory or arthritis recurs frequently, long-term corticosteroid use may be necessary, despite potential side effects.
– Pyoderma gangrenosum may show some response to oral corticosteroids.
– Local immunosuppressant and anti-inflammatory drugs in the form of creams are commonly used.
– Treatment response is usually slow, but new biologic drugs targeting IL-1 or TNF have demonstrated efficacy in individual cases.
– Acne treatment in PAPA syndrome may involve oral tetracycline antibiotics or isotretinoin, depending on the severity of the condition.
Developments in Treatment:
– Biological response modifiers, which target inflammatory proteins (cytokines), have shown success in managing other inflammatory conditions and are being explored for PAPA syndrome.
– Treatments targeting tumor necrosis factor (TNF) such as infliximab, etanercept, and adalimumab, as well as those targeting interleukin 1 (anakinra), have shown positive responses in cases of resistant arthritis and pyoderma gangrenosum.
Deemah AlHuraish, Medical Student.
Maee Barakeh, medical student