What are the other Names for this Condition? (Also known as/Synonyms)

• PAPA (Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata)
• PAPA Syndrome
• Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Syndrome

What is Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Syndrome? (Definition/Background Information)

• Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Syndrome (PAPA Syndrome) is a rare and severe inflammatory disorder affecting joints and skin. The disorder is characterized by red swollen joints, severe acne, and chronic inflammatory ulcers on skin
• The disorder is caused by mutations in the PSTPIP1 gene (that encodes a protein that regulates inflammation) and is inherited in an autosomal dominant manner. Therefore, the main risk factor for Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Syndrome is having a family history of the disorder
• The onset of PAPA is generally noted in children. It is typically diagnosed based on a combination of clinical examination, medical history evaluation, blood tests, joint fluid analysis, radiological imaging studies, and genetic testing of the PSTPIP1 gene
• The treatment of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Syndrome is typically symptomatic and supportive and may include medications such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, TNF alpha antagonists, and broader-spectrum anti-inflammatory drugs
• Currently, there are no available measures to Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Syndrome as it is a genetic condition. Genetic counseling and testing may be recommended for individuals with a family history of PAPA Syndrome and couples planning to have children
• The prognosis can vary from individual to individual but is generally improved with effective treatment. Without proper treatment, the disorder may cause severe complications that include scarring of skin, joint injury, and significant disabilities

PAPA Syndrome is one of the six pyoderma gangrenosum-associated auto-inflammatory syndromes (PGAAIS) This family of diseases includes PAPA Syndrome, PASH syndrome, PAPASH syndrome, PsAPASH syndrome, PASS syndrome, and PAC syndrome.

Who gets Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata? (Age and Sex Distribution)

• Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata (PAPA Syndrome) is a rare disorder with an early onset
• PAPA Syndrome affects both males and females
• Worldwide, all racial and ethnic groups may be susceptible to the disorder

What are the Risk Factors for Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata? (Predisposing Factors)

• The main risk factor for Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata is a positive family history of the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata? (Etiology)

The cause of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata (PAPA) is a mutation in the PSTPIP1 gene.

• A protein coded by this gene leads to an abnormal immune response
• This response generates the three diseases comprising the syndrome, Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata
• PAPA Syndrome has an autosomal dominant pattern of inheritance

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata?

The main signs and symptoms of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata include:

• Joint pain and swelling of pyogenic arthritis (or septic arthritis)
• Painful and rapidly progressing skin ulcers (pyoderma gangrenosum)
• Nodules and cysts of severe acne, also called acne conglobata. Acne conglobata can occur on the face, neck, chest, shoulders, and back

Acne conglobata does not usually develop until adolescence.

How is Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Diagnosed?

Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata (PAPA) is diagnosed based on a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition (PAPA Syndrome)
• Pyogenic arthritis is diagnosed by clinical examination, as well as imaging studies, and aspirating an affected joint (red, swollen, and tender) to examine the fluid for the presence of neutrophils, microorganisms, crystals, and culturing the fluid for bacteria and fungi/yeasts
• Pyoderma gangrenosum is a red, ulcerated skin lesion, often with associated pus. It may grow quickly. Cultures for bacteria, atypical mycobacteria, and yeast/fungi are done from the surface. Biopsies of the affected skin are done to rule out carcinoma, stain for microorganisms, and sometimes to culture the skin tissue
• Acne conglobata is usually a clinical diagnosis requiring no testing. Cultures might be done to eliminate the possibility of infection
• If PAPA Syndrome is considered, genetic testing for mutations in the PSPPIP1 gene is done

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Syndrome?

Complications of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata can include:

• Joint damage from pyogenic arthritis
• Scarring caused by the two skin components (pyoderma gangrenosum and acne conglobata)
• Significant disabilities
• Overall, decreased quality of life

How is Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Treated?

Treatment for Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata typically includes medications to reduce inflammation and prevent recurrent episodes such as 

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids
• Tumor necrosis factor (TNF) alpha antagonists infliximab, etanercept, and adalimumab have been effective. Anakinra, and Interleukin-1 antagonists can be used, as well as canakinumab.
• Broader spectrum anti-inflammatory drugs, such as methotrexate, tacrolimus, mycophenylate, and dapsone or minocycline antibiotics, have been used

How can Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata be Prevented?

Presently, it is not possible to prevent Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata Syndrome as the cause is a genetic mutation.

• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• However, early diagnosis and appropriate treatment can help manage the symptoms and prevent complications

What is the Prognosis of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata? (Outcomes/Resolutions)

The prognosis for Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata varies and depends on the severity of the disorder, the individual’s response to treatment, and any complications. 

• With proper treatment, most individuals can have an improved quality of life
• However, the disorder can cause significant discomfort and pain if left untreated

Additional and Relevant Useful Information for Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Conglobata:

The following link is a useful resource for information on other rare conditions on DoveMed:

https://www.dovemed.com/diseases-conditions/rare-disorders/