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Pyogenic arthritis-pyoderma gangrenosum-acne syndrome(PAPAS; FRA)

MedGen UID:
346801
Concept ID:
C1858361
Disease or Syndrome
Synonyms: Familial recurrent arthritis; Pyogenic arthritis, pyoderma gangrenosum and acne; Pyogenic arthritis, pyoderma gangrenosum, and severe cystic acne; Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne
SNOMED CT: Pyogenic arthritis, pyoderma gangrenosum, acne syndrome (724015007); Familial recurrent arthritis (724015007); PAPA (pyogenic arthritis, pyoderma gangrenosum, acne) syndrome (724015007); PAPA syndrome (724015007)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): PSTPIP1 (15q24.3)
 
Monarch Initiative: MONDO:0011462
OMIM®: 604416
Orphanet: ORPHA69126

Definition

A rare pleiotropic auto-inflammatory disorder of childhood, primarily affecting the joints and skin. 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. Recurrent sterile arthritis usually occurs after minor trauma, but can also occur spontaneously. PAPA syndrome is a self-limiting disease, but it can lead to severe joint destruction. The gene responsible for the syndrome is the proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1). [from SNOMEDCT_US]

Clinical features

From HPO
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
Colitis
MedGen UID:
40385
Concept ID:
C0009319
Disease or Syndrome
Ulcerative colitis is a chronic disorder that affects the digestive system. This condition is characterized by abnormal inflammation of the inner surface (epithelium) of the rectum and colon. The rectum and colon make up most of the length of the large intestine. The inflammation usually causes open sores (ulcers) to develop in the large intestine. Ulcerative colitis usually appears between the age of 15 and 30, although it can develop at any age. The inflammation tends to flare up multiple times throughout a person's life, which causes recurring signs and symptoms.\n\nThe most common symptoms of ulcerative colitis are cramping abdominal pain and frequent diarrhea, often with blood, pus, or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, bowel urgency, fatigue, and fevers. Chronic bleeding from the inflamed and ulcerated intestinal tissue can cause a shortage of red blood cells (anemia) in some affected individuals. People with this disorder have difficulty absorbing enough fluids and nutrients from their diet and often experience weight loss. Affected children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys, or liver, which are most likely due to abnormal inflammation.\n\nToxic megacolon is a rare complication of ulcerative colitis that can be life-threatening. Toxic megacolon involves a widening (dilation) of the colon and an overwhelming inflammatory response. Ulcerative colitis also increases the risk of developing colon cancer, especially in people whose entire colon is inflamed and in those who have had ulcerative colitis for 8 years or more.\n\nUlcerative colitis is one common form of inflammatory bowel disease (IBD). Another type of IBD, Crohn's disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn's disease can cause inflammation in any part of the digestive system, and the inflammation extends deeper into the intestinal tissue.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Thrombocytosis
MedGen UID:
163397
Concept ID:
C0836924
Disease or Syndrome
Increased numbers of platelets in the peripheral blood.
Microcytic anemia
MedGen UID:
1673948
Concept ID:
C5194182
Disease or Syndrome
A kind of anemia in which the volume of the red blood cells is reduced.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Cellulitis
MedGen UID:
40174
Concept ID:
C0007642
Disease or Syndrome
A bacterial infection and inflammation of the skin und subcutaneous tissues.
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
Sterile arthritis
MedGen UID:
1374751
Concept ID:
C4477044
Disease or Syndrome
An inflammatory arthritis characterized by purulent synovial fluid with neutrophil accumulation, but with negative cultures.
Cystic acne
MedGen UID:
507614
Concept ID:
C0010666
Disease or Syndrome
A severe type of acne characterized by the formation of cysts enclosing a mixture of keratin and sebum.
Allergy
MedGen UID:
9370
Concept ID:
C0020517
Pathologic Function
An allergy is an immune response or reaction to substances that are usually not harmful.
Sterile abscess
MedGen UID:
639046
Concept ID:
C0541754
Acquired Abnormality
An abscess not caused by infection with pyogenic bacteria. Operationally, a sterile abscess is inferred if investigations of an abscess fail to reveal evidence of pathogenic organisms.
Acne
MedGen UID:
152379
Concept ID:
C0702166
Disease or Syndrome
A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.
Pyoderma gangrenosum
MedGen UID:
43224
Concept ID:
C0085652
Disease or Syndrome
A deep skin ulcer with a well defined border, which is usually violet or blue. The ulcer edge is often undermined (worn and damaged) and the surrounding skin is erythematous and indurated. The ulcer often starts as a small papule or collection of papules, which break down to form small ulcers with a so called cat's paw appearance. These coalesce and the central area then undergoes necrosis to form a single ulcer.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPyogenic arthritis-pyoderma gangrenosum-acne syndrome
Follow this link to review classifications for Pyogenic arthritis-pyoderma gangrenosum-acne syndrome in Orphanet.

Recent clinical studies

Diagnosis

Dessinioti C, Katsambas A
Clin Dermatol 2017 Mar-Apr;35(2):138-146. Epub 2016 Oct 27 doi: 10.1016/j.clindermatol.2016.10.005. PMID: 28274350
Zouboulis CC
Clin Dermatol 2014 May-Jun;32(3):389-96. Epub 2013 Nov 23 doi: 10.1016/j.clindermatol.2013.11.005. PMID: 24767186

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