Pyogenic sterile arthritis, pyoderma gangrenosum, acne
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]
Synonyms and keywords:: Papa syndrome
Overview
Historical Perspective
- Papa syndrome was first discovered by Dr. Noralane M. Lindor, in 1997 following visiting several patients from three generations of a family with similar presentations.[1]
- The association between PSTPIP1 gene mutation and Papa syndrome was made in the year 2000.[2]
Classification
- There is no established system for the classification of Papa syndrome.
Pathophysiology
- The exact pathogenesis of Papa syndrome is not fully understood. However, it develops as a result of a mutation in the PSTPIP1 gene.[3]
- Mutation is inherited in an autosomal dominant mode.
- The mutation leads to a hyper-phosphorylated PSTPIP1 protein which changes its action in the inflammasome involved in interleukin-1 (IL-1β) production.
- Overproduction of IL-1β is a clear molecular feature of PAPA syndrome.
Causes
- Papa syndrome is caused by a mutation in the PSTPIP1 gene.[2]
Differentiating Papa syndrome from Other Diseases
- Papa syndrome must be differentiated from other diseases that cause arthritis, skin rash, and pyoderma gangreonosum, such as Blau syndrome, familial cold autoinflammatory syndrome and spondyloarthropathies.
- For more information on the differential diagnosis of Papa syndrome please click here.
Epidemiology and Demographics
- The prevalence of Papa syndrome is approximately 0.1 case per 100,000 individuals worldwide.[4]
- Papa syndrome commonly affects children. However, it may develop later in some individuals.
- There is no racial predilection to Papa syndrome.
- Papa syndrome affects men and women equally.
- The majority of Papa syndrome cases are reported in Europe, New Zealand, and the USA.
Risk Factors
- There are no established risk factors for Papa syndrome.
Screening
- There is insufficient evidence to recommend routine screening for Papa syndrome.
Natural History, Complications, and Prognosis
- Papa syndrome first manifests with signs and symptoms of arthritis by 1 to 10 years of age. Skin lesions usually develop later in adolescence and they tend to affect the skin of limbs.[4][5]
- The disease shows variable expressivity, as such not all the clinical characteristics, are found in an individual.
- Common complications of Papa syndrome include erosive arthritis.
- The disease severity usually decreases by the age. However, there is no data available on the prognosis of Papa syndrome.
- The disease may lead to serious joint destruction.
Diagnosis
Diagnostic Study of Choice
- There are no established criteria for the diagnosis of Papa syndrome. The diagnosis may be made clinically.[5]
- Genetic analysis and location of a mutation in the PSTPIP1 gene may be done for the confirmation of the diagnosis. However, there are reported cases of Papa syndrome with negative genetic results.
History and Symptoms
- A positive history of recurrent arthritis, skin ulceration, and acne is suggestive of Papa syndrome.[4]
- The presenting symptom of Papa syndrome is usually culture-negative arthritis.
Physical Examination
- Physical examination of patients with Papa syndrome is usually remarkable for arthritis, cystic acne, pathergy, and pyoderma gangreonosum.
- Fever may also accompany each flare of the disease.
Laboratory Findings
- Laboratory findings consistent with the diagnosis of Papa syndrome include elevated serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and WBC.[5]
- Skin lesions and joint fluid are sterile. However, synovial fluid shows neutrophilic infiltrate.
- Tumor necrosis factor-a and interleukin-1 levels has been observed to be elevated in the blood of Papa syndrome cases.[6]
Electrocardiogram
- There are no ECG findings associated with Papa syndrome.
X-ray
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with [disease name].
OR
Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
CT scan
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
MRI
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Other Imaging Findings
- There are no other imaging findings associated with Papa syndrome.
Other Diagnostic Studies
- There are no other diagnostic studies associated with Papa syndrome.
Treatment
Medical Therapy
- There is no treatment for Papa syndrome; the mainstay of therapy is supportive care.[5][7]
- Treatment options for arthritis include intraarticular corticosteroid injections.
- Oral corticosteroid may be useful for pyoderma gangreonosum.
- Anakinra (interleukin-1 antagonist) has also been observed to be effective in the management of disease flares especially arthicular symptoms.
- Adalimumab ( tumor necrosis factor (TNFα) antagonist) may be effective against cutaneous manifestations of this disorder.
Surgery
- Surgical intervention is not recommended for the management of Papa syndrome.
Primary Prevention
- There are no established measures for the primary prevention of Papa syndrome.
Secondary Prevention
- There are no established measures for the secondary prevention of Papa syndrome.
References
- ↑ Lindor, Noralane M.; Arsenault, Todd M.; Solomon, Herman; Seidman, Christine E.; McEvoy, Marian T. (1997). "A New Autosomal Dominant Disorder of Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne: PAPA Syndrome". Mayo Clinic Proceedings. 72 (7): 611–615. doi:10.4065/72.7.611. ISSN 0025-6196.
- ↑ 2.0 2.1 Yeon, Howard B.; Lindor, Noralane M.; Seidman, J.G.; Seidman, Christine E. (2000). "Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome Maps to Chromosome 15q". The American Journal of Human Genetics. 66 (4): 1443–1448. doi:10.1086/302866. ISSN 0002-9297.
- ↑ J. Smith, Elisabeth; Allantaz, Florence; Bennett, Lynda; Zhang, Dongping; Gao, Xiaochong; Wood, Geryl; L. Kastner, Daniel; Punaro, Marilynn; Aksentijevich, Ivona; Pascual, Virginia; A. Wise, Carol (2010). "Clinical, Molecular, and Genetic Characteristics of PAPA Syndrome: A Review". Current Genomics. 11 (7): 519–527. doi:10.2174/138920210793175921. ISSN 1389-2029.
- ↑ 4.0 4.1 4.2 Schellevis, M. A.; Stoffels, M.; Hoppenreijs, E. P. A. H.; Bodar, E.; Simon, A.; van der Meer, J. W. M. (2011). "Variable expression and treatment of PAPA syndrome". Annals of the Rheumatic Diseases. 70 (6): 1168–1170. doi:10.1136/ard.2009.126185. ISSN 0003-4967.
- ↑ 5.0 5.1 5.2 5.3 Dierselhuis, M. P. (2005). "Anakinra for flares of pyogenic arthritis in PAPA syndrome". Rheumatology. 44 (3): 406–408. doi:10.1093/rheumatology/keh479. ISSN 1460-2172.
- ↑ Cortis, Elisabetta; De Benedetti, Fabrizio; Insalaco, Antonella; Cioschi, Stefania; Muratori, Flaminia; D'Urbano, Leila E.; Ugazio, Alberto G. (2004). "Abnormal production of the tumor necrosis factor inhibitor etanercept and clinical efficacy of tumor in a patient with PAPA syndrome". The Journal of Pediatrics. 145 (6): 851–855. doi:10.1016/j.jpeds.2004.08.001. ISSN 0022-3476.
- ↑ Demidowich, Andrew P.; Freeman, Alexandra F.; Kuhns, Douglas B.; Aksentijevich, Ivona; Gallin, John I.; Turner, Maria L.; Kastner, Daniel L.; Holland, Steven M. (2012). "Brief Report: Genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne)". Arthritis & Rheumatism. 64 (6): 2022–2027. doi:10.1002/art.34332. ISSN 0004-3591.