PAPA syndrome
Encyclopedia
PAPA syndrome is an acronym for pyogenic arthritis
, pyoderma gangrenosum
and acne
. It is a rare genetic disorder
characterised by its effects on skin
and joints.
PAPA syndrome is inherited in an autosomal dominant fashion, which means that there is a 50% chance that a
child will inherit the disease from an affected parent.
Recently the responsible gene has been identified on Chromosome 15. 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 diseases such as familial Mediterranean fever
, Hyperimmunoglobulinemia D with recurrent fever, Muckle-Wells syndrome
, neonatal onset multisystem inflammatory disease
and familial cold urticaria
.
may be enough to make a diagnosis. Genetic testing may also be used.
at a young age, with the skin
changes more prominent from the time of puberty
.
The arthritis
is the predominant feature, noted by its juvenile onset and destructive course. Individuals often recall episodes of arthritis precipitated by a trauma
tic event. With repeated episodes the joints become damaged with multiple joint replacement
s required. Hopefully with improved treatment options the damage will be limited in new cases.
Pyoderma gangrenosum
is variably expressed, which means that it is not always present in all individuals with the disease. It presents as poorly healing ulcers 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
wound
, central venous line and intravenous drip insertion.
Acne
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.
. Treatments directed at tumour necrosis factor (TNF
) (infliximab
, etanercept
) and interleukin-1 (anakinra
) have shown a good response in resistant arthritis
and pyoderma gangrenosum
. Other traditional immunosuppressant treatments for arthritis or pyoderma gangrenosum may also be used.
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
, pyoderma gangrenosum
Pyoderma gangrenosum
Pyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
and acne
Acne
Acne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...
. It is a rare genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
characterised by its effects on skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
and joints.
Genetics
child will inherit the disease from an affected parent.
Recently the responsible gene has been identified on Chromosome 15. 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 diseases such as familial Mediterranean fever
Familial Mediterranean fever
Familial Mediterranean fever is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in MEFV, a gene which encodes a 781–amino acid protein denoted pyrin....
, Hyperimmunoglobulinemia D with recurrent fever, Muckle-Wells syndrome
Muckle-Wells syndrome
Muckle–Wells syndrome , also known as , is a rare autosomal dominant disease which causes sensorineural deafness, recurrent hives, and can lead to amyloidosis. Individuals with MWS often have episodic fever, chills, and painful joints. As a result, MWS is considered a type of periodic fever syndrome...
, neonatal onset multisystem inflammatory disease
Neonatal onset multisystem inflammatory disease
Neonatal onset multisystem inflammatory disease is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period...
and familial cold urticaria
Familial cold urticaria
Familial cold urticaria is an autosomal dominant condition characterized by rash, conjunctivitis, fever/chills and arthralgias elicited by exposure to cold - sometimes temperatures below 22°C .It has been mapped to CIAS1 and is a slightly milder member of the disease family including Muckle–Wells...
.
Diagnosis
Clinical features along with the familial tendencyFamily history
Family history is the systematic narrative and research of past events relating to a specific family, or specific families.- Introduction :...
may be enough to make a diagnosis. Genetic testing may also be used.
Clinical Features
It usually begins with arthritisArthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
at a young age, with the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
changes more prominent from the time of puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
.
The arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
is the predominant feature, noted by its juvenile onset and destructive course. Individuals often recall episodes of arthritis precipitated by a trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
tic event. With repeated episodes the joints become damaged with multiple joint replacement
Joint replacement
Replacement arthroplasty [from Greek arthron, joint, limb, articulate, + -plassein, to form, mould, forge, feign, make an image of], or joint replacement surgery, is a procedure of orthopedic surgery in which the arthritic or dysfunctional joint surface is replaced with an orthopaedic prosthesis...
s required. Hopefully with improved treatment options the damage will be limited in new cases.
Pyoderma gangrenosum
Pyoderma gangrenosum
Pyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
is variably expressed, which means that it is not always present in all individuals with the disease. It presents as poorly healing ulcers with undermined edges. Pathergy
Pathergy test
Pathergy is a cutaneous phenomenon seen with both Behçet's disease and pyoderma gangrenosum.In this condition a minor trauma such as a bump or bruise leads to the development of skin lesions or ulcers that may be resistant to healing. Pathergy can also lead to ulcerations at the site of surgical...
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
Replacement arthroplasty [from Greek arthron, joint, limb, articulate, + -plassein, to form, mould, forge, feign, make an image of], or joint replacement surgery, is a procedure of orthopedic surgery in which the arthritic or dysfunctional joint surface is replaced with an orthopaedic prosthesis...
wound
Wound
A wound is a type of injury in which skin is torn, cut or punctured , or where blunt force trauma causes a contusion . In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.-Open:...
, central venous line and intravenous drip insertion.
Acne
Acne
Acne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...
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.
Treatment
Acne treatment may require oral tetracycline antibiotics or isotretinoinIsotretinoin
Isotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
. Treatments directed at tumour necrosis factor (TNF
Tumor necrosis factors
Tumor necrosis factors refers to a group of cytokines family that can cause cell death . The first two members of the family to be identified were:...
) (infliximab
Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
, etanercept
Etanercept
Etanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...
) and interleukin-1 (anakinra
Anakinra
Anakinra is a drug used to treat rheumatoid arthritis.-Mechanism:Anakinra is an interleukin-1 receptor antagonist...
) have shown a good response in resistant arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
and pyoderma gangrenosum
Pyoderma gangrenosum
Pyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
. Other traditional immunosuppressant treatments for arthritis or pyoderma gangrenosum may also be used.