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

• PAPASH Syndrome
• PAPASH (Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa)

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

• Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa (PAPASH) is a rare genetic disorder characterized by recurrent episodes of joint pain and inflammation, skin ulcers, and severe acne (acne conglobata), as well as hidradenitis suppurativa, which is a chronic condition that causes painful boil-like lumps in 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, Acne, and Hidradenitis Suppurativa is having a family history of the disorder
• The onset of PAPASH is generally noted in older children or young adults. It is typically diagnosed based on a combination of clinical examination, blood tests to measure the levels of inflammatory markers, as needed, and genetic testing of the PSTPIP1 gene
• The treatment of Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa is typically symptomatic and supportive and may include medications such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibiotics, and biologics directed against inflammatory mediators to reduce inflammation and prevent recurrent episodes
• Currently, there are no available measures to prevent Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa as it is a genetic condition. Genetic counseling and testing may be recommended for individuals with a family history of PAPASH and couples planning to have children
• The prognosis is generally good with effective treatment. With proper treatment, most patients can have a good quality of life, but the disorder can cause significant complications if left untreated. These may include recurrent infections, joint pain, other organ and system involvement, and chronic inflammation

PAPASH 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, Acne, and Hidradenitis Suppurativa? (Age and Sex Distribution)

• Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa (PAPASH) is a rare disorder with onset in adolescence or adulthood
• PAPASH 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, Acne, and Hidradenitis Suppurativa? (Predisposing Factors)

The risk factors for Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa include:

• Having a family history of the disorder
• Inheriting a copy of the mutated PSTPIP1 gene from a parent to develop 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, Acne, and Hidradenitis Suppurativa? (Etiology)

Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa is a genetic disorder caused by mutations in the PSTPIP1 gene, which encodes a protein involved in the regulation of inflammation. 

• These mutations lead to abnormal functioning of the protein, resulting in recurrent inflammation and chronic symptoms
• The disorder 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, Acne, and Hidradenitis Suppurativa?

The signs and symptoms of Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa (PAPASH) include:

• Recurrent episodes of joint pain and inflammation
• Pyogenic arthritis or septic arthritis causing painful joint infections
• Pyoderma gangrenosum: Formation of large painful ulcers on the legs and other body regions
• Acne conglobata: A severe form of acne that results in the formation of nodules in the body; mostly in the face and neck region
• Hidradenitis suppurativa: Chronic and longstanding skin condition characterized by recurrent boil-like lumps at locations where skins rub against each other such as the groin, buttocks, under breasts, and armpits

The onset of signs and symptoms may be noted in adolescents, teens, or young adults.

How is Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa Diagnosed?

Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa is typically diagnosed based on a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition
• Blood tests to measure the levels of inflammatory markers
• Cultures and biopsies of the skin lesions to rule out infectious causes and malignancy
• Joint fluid studies
• Radiological imaging studies as required
• Genetic testing for mutations in the PSTPIP1 gene

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, Acne, and Hidradenitis Suppurativa?

Complications of Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa may include:

• Recurrent inflammatory skin lesions with purulent (pus) drainage, pain, and scarring from pyoderma gangrenosum and hidradenitis suppurativa
• Facial inflammatory lesions with scarring from acne conglobata
• Joint pain and swelling causing joint destruction
• Involvement of other organs and systems
• Chronic systemic inflammation with fever and malaise
• Overall, decreased quality of life

How is Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa Treated?

Treatment for Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa is typically symptomatic and supportive and may include medications to reduce inflammation and prevent recurrent episodes such as:

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids
• Methotrexate
• Broad-spectrum antibiotics, including sulfamethoxazole/trimethoprim, doxycycline, streptomycin, rifamycin, and clindamycin
• Isotretinoin can be useful in acne conglobata components
• Anti-inflammatory biologics: Adalimumab and infliximab have been reported to be helpful in one case. Interleukin-17 is considered the most important biochemical implicated in PAPASH. Biologics directed against IL-17 are available
• Anakinra has also been used

Smoking cigarettes is proven to worsen hidradenitis suppurativa (HS). Discontinuing smoking is recommended to improve the course of HS.

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

Presently, it is not possible to prevent Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa 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, Acne, and Hidradenitis Suppurativa? (Outcomes/Resolutions)

The prognosis for Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa (PAPASH) is generally good with proper treatment. 

• With effective treatment, most patients can have an improved quality of life
• PAPASH can cause significant discomfort and pain if left untreated
• Also, the syndrome persists if not effectively treated

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

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

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