cPAN presents with tender subcutaneous nodules, digital
gangrene, patches of purplish discoloration of the skin, blistering
and subcutaneous ulcerations
. Lesions are most often found on the knees,
back of the foot and lower leg, but other areas may also be affected including
the arms, trunk, buttocks, and the head and neck region.
In addition to the skin
problems, patients may also complain of generalized symptoms such as malaise, fever, sore throat, myalgia and
. Peripheral neurological symptoms such as tingling, numbness, weakness, sensory disturbances and absent reflexes
may also be present.
The diagnosis of cPAN is done by
. Treatment of polyarteritis nodosa
usually runs a chronic course
that can last from months to years with exacerbations and remissions.
The exact cause of cPan is not
known. Majority cases of cPAN are associated with or triggered off by certain
infections, particularly Group A streptococcus, hepatitis
Human Immunodeficiency Virus (HIV) or Parvovirus B19.
A complex interaction of auto
inflammatory and autoimmune factors, and immunodeficiency, are linked to the
development of cPAN.
Autosomal recessive mutations in the CERC1 gene may be seen in some patients with cPAN. The CERC1
gene encodes for adenosine deaminase 2 (ADA2), a plasma protein that is
important for the development and differentiation of leukocytes (white blood cells, or WBC) and
endothelial cells that line the walls of the blood vessels.
This genetic abnormality leads to deficiency in the ADA2 protein
(DADA2). ADA2 protein deficiency can also cause immunodeficiency. It can lead
to uncontrolled, chronic activity of neutrophils and damage the endothelial
cells. It is also possible to measure the levels of ADA2 protein and/or CERC1 in some centers.
A new study has suggested a
genetic cause of cPAN in some patients.
Mutations in the CERC1 gene
associated with DADA2 have been implicated in the pathogenesis of cPAN and
early-onset vasculopathy. DADA2 also affects several cellular compartments,
including B cells. However, some patients appear to have a relatively benign
and skin-limited disease.
For the study, researchers
followed two white siblings (female and male) with a history of cPAN with DADA2
as a result of mutations inherited in the CECR1 gene.
The researchers observed that
although both the study subjects were diagnosed as having
cPAN in early childhood, the onset of disease was earlier in the female sibling than the male
. They also noted that the disease
was associated with a more significant immunodeficiency and other systemic
symptoms in the female subject
than the male sibling.
These findings suggest a genetic cause of cPAN in some
patients. Therefore, DADA2 should be considered in patients with cPAN,
especially among patients whose conditions are diagnosed at an early age,
regardless of their ethnic background, presence or absence of systemic
symptoms, or family history of the disease.