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| Journal of the New Zealand Medical Association,
30-January-2004, Vol 117 No 1188
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Thymoma and immunodeficiency
Michela Di Renzo, Anna Pasqui, Fulvio Bruni, Luca Voltolini,
Paola Rottoli, Grazia Perali and Alberto Auteri
Good syndrome (GS) was first described in 1954 by Good, who
reported hypogammaglobulinaemia in a small percentage of patients with
thymoma.1 GS is a rare, adult-onset,
immunodeficiency disease characterised by hypogammaglobulinaemia, low or absent
B cells in the peripheral blood and, variably, defects in cell-mediated
immunity.2 GS was often considered a subset of
common variable immunodeficiency (CVID) with thymoma, whereas nowadays it is
regarded as a distinct clinical entity whose pathogenesis is still
uncertain.3 A bone marrow defect impairing B
cell maturation due to an aggression towards B cell precursors has been
suggested,4 and deficiencies in other cell
lineages with eosinopenia, pure red cell aplasia or neutropenia are often
reported.5
Here we report the case of a male patient who developed
recurrent respiratory tract infections for two years before being diagnosed with
GS.
Case reportA 61-year-old male presented in
March 1996 with a two-year history of
recurrent respiratory infections including otitis, bronchitis, sinusitis and two
episodes of pneumonia. Chest X-ray and chest CT scan showed a mediastinal mass,
biopsy of which revealed lymphoid cells.
The mass was resected in June 1996 and histopathologic
examination showed a mixed epithelial and lymphocytic thymoma with infiltration
of the capsule. The patient had low serum levels of IgG (24 mg/dl, normal
>700), IgM (5 mg/dl, normal >40) and IgA (5 md/dl, normal >70). The
total number of lymphocytes was normal, but the CD4+ T cell count was 420 per
ul, with an inverted CD4/CD8 ratio of 0.39 and absent peripheral B cells. PPD
skin reactivity was positive. A serological test for HIV was negative.
Two months after thymectomy, he developed pneumonia due to
Serratia marcescens, which resolved
with antibiotics. Monthly intravenous immunoglobulin (IVIG) infusions were
started at a low dosage (150 mg/kg) and the patient improved slightly. In August
1998 he presented with oral thrush, odynophagia, and a weight loss of 7 kg.
Upper gastrointestinal endoscopy revealed
Candida oesophagitis, which was treated
with itraconazole. Cough and sputum production persisted. In April 2000
Haemophilus influenzae type B was
isolated from sputum and the patient was treated with a 15-day course of
ceftriaxone. The dosage of IVIG infusion was increased (400 mg/kg every three
weeks) and the patient experienced a gradual improvement in his condition, with
decreased sputum and cough and fewer febrile episodes. A recent chest CT scan
did not show bronchiectasis.
He continues to take daily itraconazole in spite of which he
occasionally develops oral candidiasis, which resolves with local nystatin
treatment. In 2000 and 2001 immunological evaluation was repeated: CD4+ T cells
were still reduced with an inverted CD4/CD8 ratio. In vitro lymphocyte
proliferation was normal. Intracellular IL2 and IFN-γ cytokine production
was normal. He also has mild neutropenia
(1200/mm3).
DiscussionGS was one of the first
immunodeficiency diseases to be classified.1
Patients with GS are usually middle-aged or elderly when they develop recurrent
infections, most frequently of the respiratory tract. It is usually the
infections rather than the local symptoms due to the mediastinal mass that call
attention to the possibility of thymoma. Only 3–6% of patients with
thymoma are, however, hypogammaglobulinaemic and the relationship between
thymoma and the immune dysfunction is not
clear;6 thymoma does not seem to induce
hypogammaglobulinaemia because after it is surgically removed the immune
impairment persists, as in our patient who, after thymectomy, continued to be
hypogammaglobulinaemic.
The deficient humoral immunity in GS is the main cause of
the recurrent respiratory infections, with an overall spectrum of manifestations
and pathogens similar to other hypogammaglobulinaemic conditions, such as
CVID.7 However, in GS opportunistic infections,
such as mucocutaneous candidiasis (as seen in our patient), herpes zoster,
Pneumocystis carinii pneumonia and
recurrent herpes simplex virus infections develop more frequently than in
CVID.8 The occurrence of opportunistic
infections in GS seems to be due to defects in cell-mediated immunity, which
have been found in several patients.9 In our
patient, CD4+ T cells were reduced with an inverted CD4/CD8 ratio but he also
had a mild neutropenia, which may also contribute to the recurrence of mycotic
infections.
Several haematological disorders have been reported in GS,
including pure red cell aplasia, pancytopenia, and autoimmune haemolytic
anaemia.5 The target in many of these disorders
appears to be the stem cell committed to a haemopoietic lineage with loss of
that lineage, even if the role of autoantibody-mediated mechanisms in the
destruction of the lineage cannot be
excluded.9
Finally, our case report confirms the importance of IVIG
replacement in GS at appropriate doses in order to improve the control of
infections and perhaps prevent the development of
bronchiectasis,10 which to date has not been
identified in our patient.
Author information:
Michela Di Renzo, Internal Medicine Physician; Anna L Pasqui, Cardiologist;
Fulvio Bruni, Cardiologist, Department of Internal Medicine and Immunological
Sciences; Luca Voltolini, Thoracic Surgeon, Department of Thoracic Surgery;
Paola Rottoli, Respiratory Physician; Grazia Perali, Biologist, Department of
Respiratory Diseases; Alberto Auteri, Immunologist, Department of Internal
Medicine and Immunological Sciences, University of Siena, Siena, Italy
Correspondence: Dr
Michela Di Renzo, Dipartimento di Medicina Interna e Scienze Immunologiche,
Policlinico Le Scotte, 53100 Siena, Italy. Fax: +3 905 774 4114; email: cd28apo@hotmail.com
References:
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