Immunodeficiency associated with tumour pathology: Good’s syndrome

Abstract

The Good’s syndrome (GS) is a low prevalence entity where thymoma often is associated with immunodeficiency. Patients may start presenting recurrent rhinosinusal infections, bronchopulmonary infections, haematological alterations and diarrhoea, secondary to immunodeficiency. They can also present respiratory symptoms and parathymic syndromes derived from the existence of thymoma, a slow-growing neoplasm located in the anterior mediastinum. We present the case of a 76-year-old man diagnosed with thymoma by image analysis, which had presented multiple episodes of pneumonia and two admissions to the hospital for diarrhoea of weeks of evolution. After finishing the study, the patient is diagnosed of GS. In this case, thymectomy prevented the appearance of parathymic syndrome, but without any effect on immunodeficiency symptoms. To decrease repeat infections, substitution therapy with immunoglobulins was started. The prognosis will depend mainly on the recurrent infectious and to a lesser extent on the thymic neoplasm.

Background

Good’s syndrome (GS) is a rare disease that often goes unnoticed in the differential diagnosis of pathologies that present with immunodeficiencies. Its diagnosis and early treatment can save lives, so it is important to talk about this disease

Case presentation

GS is a low-prevalence entity that associates the existence of thymoma with a humoural immunodeficiency. This disorder is characterised by hypogammaglobulinaemia associated with a marked decrease of B lymphocytes in patients with a thymoma. There may also be an inverted T lymphocyte, CD4/CD8 ratio. Patients have a high susceptibility to opportunistic bacterial, viral and mycotic infections. Tumour resection in general does not improve immunodeficiency. The aetiology of this association is unknown. Thymoma is usually associated with other entities like myasthenia gravis (15%) and pure red series aplasia (PRSA, 5%–10%). On the other hand, 50% of PRSA are related to thymoma and GS represents only 0.2% of all immunodeficiencies.¹

Our case is about a 76-year-old man, without known allergies and a personal history of hypertension, hypercholesterolaemia, chronic obstructive pulmonary disease, non-allergic chronic rhinosinusitis, benign prostatic hypertrophy and obesity. In June 2013, he was admitted in the digestive service for two episodes of chronic diarrhoea of about 8 months of evolution. Subsequently, he was diagnosed of non-specific pancolitis after an endoscopic study. Only intestinal superinfection by Campylobacter jejuni was observed. Afterwards, he suffered three episodes of methicillin-resistant Staphylococcus aureus pneumonia. A chest CT scan was performed, where small-calibre bronchiectasis at the lung bases and a solid multilobulated mass of approximately 41×25 mm were observed (figure 1). Biopsy of the surgical specimen was diagnosed as cortical thymoma of polygonal cells, WHO B2 (figure 2). This tumour was minimally invasive and was well delimited by fibrous capsule, in which two focus of microinvasion were identified.

Figure 1.

Chest CT scan with small-calibre bronchiectasis at the lung bases and a solid multilobulated mass of approximately 41×25 mm.

Figure 2.

Cortical thymoma of polygonal cells, WHO B2. This tumour was minimally invasive and was well delimited by fibrous capsule, with two focus of microinvasion.

The patient did not present anaemia or renal or hepatic profile alterations. The physical examination showed a regular state, mild tachycardia without alteration of other vital signs, mild respiratory distress, abdominal thoracoabdominal disbalance and oxygen saturation of 90%. Poorly effective cough. He tolerated decubitus. He did not present hepatojugular reflux at 45°. Cardiac examination was normal. Pulmonary auscultation was abnormal with bilateral basal crackles. Abdominal and upper and lower limb examination was normal.

Analytical study showed low serum levels of IgA (<5 mg/dL), IgM (5.3 mg/dL) and IgG (74 mg/dL) and decrease in IgG subclasses (IgG₁ <164 mg/dL, IgG₂ <20 mg/dL, IgG₃ 6 mg/dL and IgG₄ <3 mg/dL). The proteinogram showed a hypogammaglobulinaemia without observing a monoclonal component. Lymphocyte populations showed a severe decline in CD19+ B lymphocytes (2 cells/µL). Studies of HIV and hepatitis B were negative.

He remained hospitalised for 2 weeks and he was treated for pneumonia with linezolid without complications. It was then decided to start replacement therapy with IgG 45 mg intravenous (the recommended initial dose is 0.4–0.8 g/kg in a single dose). Treatment was initially given every 3 weeks and later every 4 weeks due to a good clinical evolution. After 5 months of treatment, an adequate restoration of IgG was observed (877 mg/dL). Subsequently, outpatient controls have been performed. Treatment is given regularly, and no new infections have been reported for 4 years.

Treatment

Thymectomy prevented the appearance of parathymic syndrome and vena cava syndrome but does not improved immunodeficiency. To decrease repeat infections, substitution therapy with immunoglobulins was prescribed.

Outcome and follow-up

Outpatient controls have been performed. Treatment is given regularly, and no new infections have been reported for 4 years.

Discussion

GS was described in 1954 by Robert Good. This disease usually occurs in the fourth or fifth decade of life. Although the diagnosis is made according to established clinical criteria, the existence of an abnormal protein related to the proliferation and differentiation of B cells has been observed.^{2 3} This patient presented with chronic non-specific diarrhoea, recurrent lung and sinus infections. These signs associated with the finding of thymoma, the decrease of CD19+ B cells and the decrease of immunoglobulins, meet criteria for the diagnosis of GS.

Learning points.

• This disease may begin with a parathymic syndrome or develop recurrent and opportunistic infections. They often present a more unfavourable prognosis than other immunodeficiencies such as common variable immunodeficiency or X-linked agammaglobulinaemia.

• The study in patients with recurrent infections and thymoma should include lymphocyte populations and quantitative study of immunoglobulins and subpopulations, given the possibility of presenting this disease.

• Thymectomy does not improve recurrent infections and only relieves parathymic syndrome if they appear. However, rapid recognition of this disease, correct antibiotic treatments and replacement therapy with immunoglobulins can achieve clinical stability and stop disease progression.