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Disease Profile

Pyogenic arthritis, pyoderma gangrenosum and acne

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

-

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

PAPA syndrome; Pyogenic arthritis, pyoderma gangrenosum, and severe cystic acne; PAPAS;

Categories

Congenital and Genetic Diseases; Immune System Diseases; Musculoskeletal Diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 69126

Definition
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome is a rare pleiotropic autoinflammatory disorder of childhood, primarily affecting the joints and skin.

Epidemiology
To date, only 34 patients with PAPA syndrome have been reported worldwide, from five families (two in the USA, one in Italy, one in the Netherlands, and one in New Zealand).

Clinical description
The first affected family contained ten affected members from three generations and manifested variable expression of a pauciarticular, nonaxial, arthritis that began in childhood; pyoderma gangrenosum; and severe cystic acne in adolescence and beyond. PAPA syndrome is a self-limiting disease, but it can lead to severe joint destruction. Synovial fluid is purulent with neutrophil accumulation, but cultures are invariably negative. Recurrent sterile arthritis usually occurs after minor trauma, but can also occur spontaneously. Other less commonly associated features include adult-onset insulin-dependent diabetes mellitus, proteinuria, and abscess formation at the site of parenteral injections (pathergy).

Etiology
The gene responsible for the syndrome, the proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) gene (previously known as the CD2 binding protein 1 (CD2BP1) gene), was cloned in 2002. Only two mutations account for the known cases. Recently, the PSTPIP1 protein has been demonstrated to bind pyrin/marenostrin (P/M), the protein encoded by the MEFV gene, mutations in which cause Familial Mediterranean Fever. PAPA-associated PSTPIP1 mutants exhibit increased binding to P/M.

Differential diagnosis
Differential diagnosis for PAPA syndrome should include juvenile idiopathic arthritis and periodic fever.

Genetic counseling
PAPA syndrome is inherited in an autosomal dominant manner.

Management and treatment
Arthritis and skin lesions have sometimes been reported to be responsive to glucocorticoids. However, two alternative therapeutics have been suggested so far. In one report, the disease underwent rapid and sustained clinical remission after treatment withthe tumor necrosis factor inhibitor, etanercept. Another recent paper described the effect of recombinant human interleukin (IL)-1 receptor antagonist (anakinra), which appeared to be an effective therapy to treat disease flares in PAPA syndrome.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Acne
0001061
Arthritis
Joint inflammation
0001369
Fatigue
Tired
Tiredness

[ more ]

0012378
Fever
0001945
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Pustule
Pimple
0200039
Skin ulcer
Open skin sore
0200042
30%-79% of people have these symptoms
Arthralgia
Joint pain
0002829
Increased circulating antibody level
0010702
Lymphadenopathy
Swollen lymph nodes
0002716
5%-29% of people have these symptoms
Crohn's disease
0100280
Myositis
Muscle inflammation
0100614
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
Type I diabetes mellitus
Type 1 diabetes
Type I diabetes

[ more ]

0100651
1%-4% of people have these symptoms
Allergy
0012393
Cellulitis
Bacterial infection of skin
Skin infection

[ more ]

0100658
Colitis
0002583
Cystic acne
0033188
Elbow flexion contracture
Contractures of elbows
Elbow contracture
Elbow contractures

[ more ]

0002987
Elevated C-reactive protein level
0011227
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Knee flexion contracture
0006380
Microcytic anemia
0001935
Pyoderma gangrenosum
0025452
Sterile arthritis
0040310
Thrombocytosis
Increased number of platelets in blood
0001894
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Pancytopenia
Low blood cell count
0001876
Sterile abscess
0025616

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Pyogenic arthritis, pyoderma gangrenosum and acne. Click on the link to view a sample search on this topic.