pyogenic arthritis-pyoderma gangrenosum-acne syndrome

Pyogenic arthritis-pyoderma gangrenosum-acne (PAPA) syndrome is an autoinflammatory condition that chiefly affects the joints and skin, leading to painful episodes of sterile arthritis and severe inflammatory skin disease. It is caused by disease-causing variants in the PSTPIP1 gene, which alter regulation of the innate immune system and trigger excessive inflammation. Symptoms usually begin in early childhood, although some people first come to medical attention later in life. The condition is very rare, affecting fewer than one in a million people worldwide.

Inflammatory joint problems are a hallmark of PAPA syndrome. Children often present with sudden, painful swelling of large joints such as the knees, ankles, or elbows. These episodes are sterile, meaning no bacteria are found, yet recurrent inflammation can lead to elbow and knee flexion contractures and limitation of movement over time. Skin involvement is equally prominent. Many individuals develop pyoderma gangrenosum, a rapidly enlarging ulcer of the skin, as well as recurrent pustules, cellulitis, and cystic or severe acne that may leave scarring. Because skin ulcers can be slow to heal, long-term wound care is frequently required. The disorder also has systemic features of inflammation. Fevers, fatigue, elevated C-reactive protein, thrombocytosis, and microcytic anemia are often documented during flares. Some people experience hepatosplenomegaly or enlarged lymph nodes. The gastrointestinal tract can be involved, and a small subset develop colitis or Crohn’s disease-like inflammation. Not all individuals experience all features, and severity varies considerably. Some have occasional joint flares with mild skin disease, while others face lifelong cycles of painful arthritis and extensive ulcers.

PAPA syndrome results from pathogenic variants in the PSTPIP1 gene. The PSTPIP1 protein interacts with components of the cytoskeleton and several immune signaling molecules; altered function disrupts control of the innate immune response, leading to unchecked inflammation in joints, skin, and other tissues. The condition is inherited in an autosomal dominant pattern, meaning a person needs only one altered copy of the gene to be affected. When a parent carries the variant, each child has a 50 percent chance of inheriting it. Even within the same family, the type and severity of symptoms can differ markedly, a phenomenon known as variable expressivity. Genetic counseling is recommended for affected individuals and their relatives to discuss testing, family planning, and early recognition of symptoms.

Currently, management focuses on controlling inflammation, preventing joint damage, and promoting healing of skin lesions. During flares, physicians may use anti-inflammatory medications or short courses of systemic corticosteroids. Some individuals benefit from immune-modulating agents that target specific inflammatory pathways, prescribed and monitored by a rheumatologist or dermatologist. Long-term care relies on a multidisciplinary team that may include rheumatology, dermatology, gastroenterology, wound-care nursing, and physical therapy. Regular surveillance for joint mobility, skin integrity, blood counts, and markers of systemic inflammation helps clinicians gauge disease activity and adjust therapy promptly. Physical and occupational therapy can maintain range of motion and reduce the risk of contractures. Because treatment needs differ from person to person, families should work closely with specialists experienced in autoinflammatory diseases to tailor a plan that addresses current symptoms while monitoring for potential complications.

The course of PAPA syndrome is usually chronic and episodic. Many people experience recurrent flares of joint or skin inflammation interspersed with quieter periods, and the intensity of symptoms can change over time. Joint contractures or scarring from ulcers may impact daily activities, yet early recognition and aggressive treatment of flares can limit permanent damage. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with experienced specialists and genetic counselors, as coordinated care and timely adjustments in therapy can make a meaningful difference in long-term quality of life.

PAPA syndrome is an active research area with numerous ongoing clinical trials aimed at refining immune-modulating treatments and understanding disease mechanisms. Individuals interested in participating in research can search ClinicalTrials.gov or discuss eligibility with their healthcare team.