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PAPA syndrome is a rare
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...
characterised by its effects on
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
and
joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...
s. The acronym ''PAPA'' stands for pyogenic arthritis,
pyoderma gangrenosum Pyoderma gangrenosum is a rare, Inflammation, inflammatory skin disease where painful pustules or skin condition, nodules become ulcer (dermatology), ulcers that progressively grow. Pyoderma gangrenosum is not infectious. Treatments may include ...
and
acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...
.


Signs and symptoms

PAPA syndrome usually begins with
arthritis Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...
at a young age, with the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
changes more prominent from the time of
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...
. The arthritis is the predominant feature, noted by its juvenile onset and destructive course. Individuals often recall episodes of arthritis precipitated by a traumatic event. With repeated episodes the joints become damaged with multiple
joint replacement Joint replacement is a procedure of orthopedic surgery known also as arthroplasty, in which an arthritic or dysfunctional joint surface is replaced with an orthopedic prosthesis. Joint replacement is considered as a treatment when severe joint pai ...
s required. Hopefully, with improved treatment options, the damage will be limited in new cases.
Pyoderma gangrenosum Pyoderma gangrenosum is a rare, Inflammation, inflammatory skin disease where painful pustules or skin condition, nodules become ulcer (dermatology), ulcers that progressively grow. Pyoderma gangrenosum is not infectious. Treatments may include ...
is variably expressed, which means that it is not always present in all individuals with the disease. It presents as poorly healing
ulcers An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing ...
with undermined edges. Pathergy is an important feature (this term refers to the tendency of ulcers to arise at points of injury). There are reports of lesions developing at the site of a
joint replacement Joint replacement is a procedure of orthopedic surgery known also as arthroplasty, in which an arthritic or dysfunctional joint surface is replaced with an orthopedic prosthesis. Joint replacement is considered as a treatment when severe joint pai ...
wound A wound is any disruption of or damage to living tissue, such as skin, mucous membranes, or organs. Wounds can either be the sudden result of direct trauma (mechanical, thermal, chemical), or can develop slowly over time due to underlying diseas ...
, central venous line and
intravenous drip Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
insertion.
Acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...
affects most individuals with PAPA syndrome but to a variable degree. It is usually of a severe nodulocystic type which if untreated results in
scarring A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a nat ...
.


Genetics

PAPA syndrome is inherited in an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
fashion, which means that if one parent is affected, there is a 100% chance that a child will inherit the disease from a homozygous affected parent and a 50% chance that a child will inherit the disease from an affected heterozygous parent. The responsible gene has been identified on
chromosome 15 Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 99.7 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DNA ...
. Two mutations have been found in a protein called CD2 binding protein 1 (CD2BP1). This protein is part of an inflammatory pathway associated with other
autoinflammatory disease Periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythematosus, in which the disease is caused by abnormalities o ...
s such as
familial Mediterranean fever Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in the Mediterranean fever (MEFV) gene, which encodes a 781–amino acid protein called pyrin. While all ethnic ...
, hyperimmunoglobulinemia D with recurrent fever,
Muckle–Wells syndrome Muckle–Wells syndrome (MWS) is a rare autosomal dominant disease which causes sensorineural deafness and recurrent hives, and can lead to amyloidosis. Individuals with MWS often have episodic fever, chills, and joint pain. As a result, MWS i ...
, neonatal onset multisystem inflammatory disease, and familial cold urticaria.


Diagnosis

Clinical features along with the familial tendency may be enough to make a diagnosis.
Genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
may also be used.


Treatment

Acne treatment may require oral
tetracycline antibiotics Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. ...
or
isotretinoin Isotretinoin, also known as 13-''cis''-retinoic acid and sold under the brand name Accutane among others, is a medication used to treat skin diseases like harlequin-type ichthyosis, and lamellar ichthyosis, and severe cystic acne or moderat ...
. Treatments directed at
tumor necrosis factor Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
( TNF) (
infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing ...
,
etanercept Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. ...
) and
interleukin-1 The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults. Discovery Discovery of these cytokines began with studies on t ...
( anakinra) have shown a good response in resistant
arthritis Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...
and
pyoderma gangrenosum Pyoderma gangrenosum is a rare, Inflammation, inflammatory skin disease where painful pustules or skin condition, nodules become ulcer (dermatology), ulcers that progressively grow. Pyoderma gangrenosum is not infectious. Treatments may include ...
.Dierselhuis MP, Frenkel J, Wulffraat NM, Boelens JJ. Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology (Oxford). 2005 Jan 5;(Epub ahead of print) Other traditional immunosuppressant treatments for arthritis or pyoderma gangrenosum may also be used.


See also

*
List of cutaneous conditions Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the Human body, body and composed of Human skin, skin, hair, Nail (anatomy), nails, and related muscle and glands. The major function o ...
*
Psoriatic arthritis Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that may occur in some people affected by the autoimmune disease psoriasis. The classic features of psoriatic arthritis include dactylitis (sausage-like swelling of the fingers ...
* SAPHO syndrome


References


External links

{{DEFAULTSORT:Papa Syndrome Autosomal dominant disorders Rare diseases Syndromes Arthritis Acneiform eruptions Reactive neutrophilic cutaneous conditions Autoinflammatory syndromes