ARTICLE
Eosinophilic fasciitis was described over a quarter
of a century ago [1]. It is uncommon in females and in children [2], and
the main feature is represented by massive thickening of the subcutaneous
fascia, with eosinophil infiltration, resulting in indurative swelling
of the skin affecting mainly the arms and legs, and intermittent blood
eosinophilia [3]. Symptoms of weakness and pain, and progressive motor
limitation are the main complaints referred to by patients. Histological
examination of full thickness biopsies reveals the primary pathological
alterations as occurring in the fascia and not in the skin. A favourable
response to oral corticosteroids has usually been reported [3]. The etiology
of this condition is unknown, even if a recent history of excessive physical
exertion, febrile flu-like illness or increased ingestion of L-tryptophan
have all been postulated as possible causes [3]. The association of immunological
defects and eosinophilic fasciitis has been reported, and one case had
hypogammaglobulinemia [4]. Here we describe another case of eosinophilic
fasciitis occurring in a patient with common variable immunodeficiency
(CVI).
Case report
The patient, a 53-year-old female, was admitted to the Dermatology Clinic
of the University of Chieti in November 1998, for the development of an
infiltrative red-coloured lesion of the skin in the malleolar region of
the left foot which slowly enlarged to the medial left leg, with itching
and pain. Similar manifestations were found in the right inguinal fold,
the right ankle, and the upper right arm, without pain.
In the patient's history there were three successful pregnancies with
normal delivery, and an episode of post-partum thrombosis and phlebitis
of the left saphena, associated with left lung pleurisy occurring after
the third pregnancy. Hysterectomy was performed at the age of 30. At the
age of 40, the patient underwent a surgical correction for carpal tunnel
syndrome.
Physical examination revealed only enlarged abdomen (the patient was
overweight, 73 kg), with pain in right iliac fossa, and brownish indurated
cutaneous lesions of the left leg which were biopsied, right inguinal
fold, right ankle, and upper right arm. The histology demonstrated a thickened
fascia with inflammatory infiltrate, including eosinophils (Fig.
1), without muscle involvement. The infiltrate comprised also lymphocytes
and plasma cells. X-ray findings showed obliteration of the left costal
sinus due to previous pleurisy. Normal esophageal transit was observed
after barium intake. Eosinophils were 524 cells/mul, and serum electrophoresis
showed reduced gammaglobulin (466 mg/dl). The patient was then discharged
with the diagnosis of eosinophilic fasciitis, and given oral griseofulvin
500 mg and chloroquine 200 mg b.i.d. plus 4 mg methylprednisolone daily.
The patient was readmitted to our hospital in March 1999, showing improvement
of the cutaneous indurated lesions, which still persisted on the left
shoulder and arm, the left ankle and the medial region of the left leg,
and the upper part of the right leg, with induration. All biochemical,
hematological and autoantibody tests were normal. At that time, serum
immunoglobulin levels were investigated. The results are shown in Table
I and demonstrate panhypogammaglobulinemia. These findings were confirmed
in January 2000, after the patient had discontinued steroid treatment
in June 1999, when gammaglobulins were 390 mg/dl and eosinophils had returned
to normal levels (380 cells/mul) (Table
I). A diagnosis of CVI was therefore made. Lymphocyte subset study
showed repeatedly low B cell numbers (4%, absolute n° 64/mul) and
reduced CD4+ T cells (440 and 376/mul in September '99 and
January 2000), with reversed CD4/CD8 ratio (0.57 and 0.6, normal value
1.2-1.6). Twelve percent of CD4+ T cells expressed the IL-2R
(CD25) and only 2% the CD45RA marker.
Discussion
Both CVI and eosinophilic fasciitis represent uncommon diseases. CVI
is a primary immunodeficiency disorder characterized by a variable decrease
(two or more standard deviations from the normal mean) of IgG, IgA and/or
IgM and heterogeneous clinical features [5]. Its cause is unknown, although
both a genetic predisposition and dysregulation of cytokine production
have been postulated. The phenotypic defect is a failure in B cell differentiation,
inducing reduction of Ig secretion. An accelerated peripheral B cell apoptosis
may also be involved in B cell depletion [6]. T cell abnormalities include
decrease of lymphocyte proliferation, a defect in the early phase of T
cell activation, deficiency of antigen-primed T cells, and reduced production
and/or expression of IL-2 and other cytokines [5]. In our patient, CVI
was diagnosed by chance observation of persistently low levels of all
Ig classes, unrelated to protein loss or immunosuppressive treatment.
The diagnosis was made one year after the appearance of eosinophilic fasciitis,
which is usually characterized by hypergammaglobulinemia [2-4]. In the
skin biopsies, along with eosinophilic infiltrate, plasma cells were also
identified, but they could not locally contrast the central failure of
B cell differentiation into Ig-producing cells. The presence of B lymphocytes
and the reversed CD4/CD8 ratio are other factors described in CVI [5].
Only one case of association between CVI and eosinophilic fasciitis has
been previously reported [4], although patients with selective IgA deficiency
- a condition often related to CVI - have also been described.
Skin diseases most frequently associated with CVI are granulomatous
disorders, such as those due to infections, subcutaneous nodules, erythema
nodosum or vasculitic lesions and Raynaud's phenomenon. On the contrary,
the association of eosinophilic fasciitis with primary immunodeficiencies
is apparently rare, but since both conditions are also rare, an increased
rate of simultaneous occurrence can be hypothesized. Our description may
prompt others to validate this assumption.
Article accepted on 1/6/01
REFERENCES
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and decreased IgG and IgA production. Cell Immunol 1995; 166: 83-92.
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