ANSWER TO FELLOW´S CHALLENGE (September-October Issue, 2004)
Correct answers: 1) B or C
Diagnosis: Sarcoidosis or common
variable
immunodeficiency (CVID)
This PROJ challenge turned out to be more challenging and complex
than anticipated when it was first
published online in November
2004. The case of this 13 year
old white male with non-caseating granulomas and hemolytic anemia has continued to evolve
over time, and his diagnosis has changed/expanded
during the past two months.
The patient´s liver biopsy revealed non-caseating granulomas, and his chest CT showed scattered small lung nodules and adenopathy. These findings
were suggestive of a diagnosis of
sarcoidosis. However, he also
had autoimmune
hemolytic anemia which, although
described, is extremely rare in sarcoidosis. It should be noted that autoimmune hemolytic anemia is reported more commonly
in CVID (5-7% of patients) than in sarcoidosis.
Granulomatous disease is also described in patients with
CVID. Moreover, the patient had
a history of recurrent respiratory tract
infections (bronchitis, one pneumonia, as well as a
few episodes of sinusitis, which was inadvertently
omitted from the published history summary in the previous
issue). This further raised concern
of CVID. Initially, Wegener´s granulomatosis was seriously considered in the differential diagnosis because
of the pulmonary findings and the history of sinusitis, but the absence
of any necrotizing granuloma on the liver biopsy decreased suspicion of this
diagnosis.
The patient´s pertinent laboratory results included a normal
angiotensin converting enzyme level and
negative anti-neutrophil cytoplasmic antibodies. His IgG and IgA levels were depressed.
T-cell function studies were normal.
Only two weeks prior to the publication of this current PROJ
issue, the patient presented again to his local
hospital, this time with an enlarged cervical lymph node which was biopsied. Pathology studies showed non-Hodgkin´s
lymphoma. His previous liver and bone biopsies were reviewed
at another medical center to look for
evidence of malignancy, but were negative for this. Review of the liver biopsy also confirmed the presence of non-caseating
granuloma. It is certainly possible that this patient´s
primary diagnosis is lymphoma. Hemolytic anemia is known to occur in patients with lymphoma, but the finding
of non-
caseating granuloma would not be expected.
Clinical complications reported in CVID include: recurrent
infection (especially respiratory and gastrointestinal
tracts); autoimmune disease (autoimmune cytopenia, inflammatory bowel
disease, rheumatoid arthritis), granulomatous disease, malignancy (most
commonly lymphomas and gastrointestinal adenocarcinomas). In addition to having decreased quantitative
immunoglobulins, this patient had several of the clinical
problems associated with CVID (recurrent respiratory tract infections, autoimmune
hemolytic anemia, granulomatous disease and lymphoma).
However, there are some aspects of this case which are unexpected in CVID. Of note are the patient´s normal T-cell
function studies. Deficient lymphocyte proliferation to mitogens
is frequently seen in CVID, particularly in patients
with granulomatous disease. Furthermore, although lymphoma is not an uncommon complication (incidence
of 6- 8%),
it is reported much more commonly in
women and older adults. Despite
these inconsistencies, CVID is the diagnosis
that best fits the course of this complex and unfortunate patient.
We would add a takeaway message. The differential diagnosis
of a child with a granulomatous disease is fraught
with pitfalls and challenges when he/she presents to a pediatric rheumatologist. In many
countries tuberculosis is the first concern, but if it is not TB, sarcoid, CVID, and malignancies
must be kept in mind.
Articles of interest:
1. Lee AH, Levinson AI, Schumacher
HR Jr. Hypogammaglobulinemia
and rheumatic disease. Sem Arthritis Rheum. 1993;22:252-64
2. Arkwright
PD, Abinun M, Cant AJ. Autoimmunity in human primary immunodeficiency disease. Blood 2002;99:2694-2702
3. Mechanic LJ, Dikman S, Cunningham-Rimdles C.
Granulomatous disease in common variable immunodeficiency. Ann Int Med 1997;127:613-617,
Regarding the fellows´ responses, most selected sarcoidosis,
and a few chose
CVID. Given the changing and unclear course of this patient, no winner
was
selected for this month´s challenge. Our apologies. |
