Good Syndrome

Good syndrome is the combination of thymoma and adult onset hypogammaglobulinaemia with combined B and T cell defects. It presents at 40 to 70 years with infections.

Pathophysiology. Thymoma related disruption leads to pre-B cell arrest in the bone marrow, so B cells are absent or very low and immunoglobulins fall. CD4 lymphopenia with an inverted CD4:CD8 ratio and weak T cell function add opportunistic infection risk.

About 6 to 11% of patients with thymoma develop hypogammaglobulinaemia.

Thymectomy removes the tumour but does not restore immunity.

• Recurrent sinusitis, bronchitis, pneumonia and bronchiectasis with encapsulated bacteria
• Opportunistic infection: cytomegalovirus (retinitis, colitis), Pneumocystis jirovecii, herpes zoster and simplex, mucocutaneous candidiasis, mycobacteria
• Chronic diarrhoea
• Pure red cell aplasia (pallor, fatigue, low reticulocytes)
• Myasthenia gravis, lichen planus, neutropenia, aplastic anaemia, other autoimmunity
• Chest symptoms or an incidental mediastinal mass

• Contrast CT or MRI of the chest for an anterior mediastinal mass, with biopsy or resection for histology (thymoma types AB and B1 to B3, and staging by Masaoka stage).
• Immunoglobulins: low IgG, IgA and IgM.
• Lymphocyte subsets: absent or very low B cells (CD19 positive), CD4 lymphopenia, inverted CD4:CD8 ratio, with reduced T cell proliferation.
• Opportunistic infection screen: CMV PCR in blood, HIV test, Pneumocystis PCR on respiratory samples when there are chest signs, and serology for hepatitis B and C.
• Anaemia workup: reticulocyte count, parvovirus B19 PCR, bone marrow examination for pure red cell aplasia (absent erythroid precursors with normal other lines).
• Acetylcholine receptor antibodies before surgery, to find occult myasthenia gravis.

Differential diagnosis.

• Common variable immunodeficiency
• X-linked agammaglobulinaemia (adult presentation unlikely)
• Secondary hypogammaglobulinaemia (chronic lymphocytic leukaemia, lymphoma, myeloma, protein loss, drugs)
• HIV infection
• Thymoma without immunodeficiency
• Idiopathic CD4 lymphocytopenia

• Thymectomy for resectable thymoma, after myasthenia is excluded or controlled. Radiotherapy or chemotherapy is added for invasive disease by stage.
• Immunoglobulin replacement for life: intravenous immunoglobulin 400 to 600 mg/kg every 3 to 4 weeks, or subcutaneous immunoglobulin 100 to 150 mg/kg weekly. Adjust to a trough IgG of at least 6 g/L, usually 7 to 9 g/L, and higher with bronchiectasis. Check the trough every 3 to 6 months. Slow the infusion rate after any reaction; for anaphylaxis give adrenaline 0.5 mg intramuscularly.
• Pneumocystis prophylaxis while CD4 lymphopenia persists: co-trimoxazole 960 mg orally three times weekly.
• Herpesvirus prophylaxis: aciclovir 400 mg orally twice daily for recurrent herpes simplex or zoster (reduce dose at creatinine clearance under 25 mL/min).
• CMV disease: valganciclovir 900 mg orally twice daily for 21 days, then 900 mg once daily as maintenance while immunodeficient (reduce at creatinine clearance under 60 mL/min, with blood count monitoring every week for neutropenia). For severe disease start ganciclovir 5 mg/kg intravenously every 12 hours, adjusted to renal function.
• Pure red cell aplasia: ciclosporin 3 to 5 mg/kg orally daily in two doses, targeting a trough of 100 to 200 microgram/L, with or without prednisolone 1 mg/kg daily (maximum 60 mg). Monitor creatinine, blood pressure and magnesium. Transfuse irradiated, leukodepleted red cells when needed.
• Treat bacterial infection early by culture, using longer courses.
• Vaccines: inactivated influenza yearly and pneumococcal conjugate vaccine; avoid live vaccines.
• Treat myasthenia gravis and other autoimmune disease in the usual way.

Special groups.

• Patients with myasthenia gravis: anaesthetic and perioperative plans need neurology and anaesthetic input.

Monitoring. Trough IgG, full blood count and creatinine every 3 to 6 months. CMV PCR monthly while symptomatic or on immunosuppression. CT chest at 6 months and then yearly for 5 years after resection for recurrence.

Referral and escalation. Refer to immunology, thoracic surgery and oncology. Urgent for opportunistic infection, severe anaemia, or respiratory compromise.