The Journal of the Arkansas Medical Society Med Journal May 2019 Final 2 - Page 20

CASE STUDY Good’s Syndrome: It’s Good to Have a Diagnosis Naga Saranya Addepally, MD ABSTRACT ood’s syndrome is a rare condi- tion with combined immunodefi- ciency and thymoma. We present a G patient with severe, chronic diarrhea and history of thymoma. Workup showed markedly reduced lev- els of immunoglobulins. Treatment with intravenous immunoglobulins resulted in significant improve- ment in diarrhea and weight gain. Keywords: Good’s syndrome; Thymoma; Hy- pogammaglobulinemia INTRODUCTION Good’s syndrome (GS) is a rare disorder char- acterized by combined humoral and cellular im- munodeficiency associated with thymoma. It mani- fests a variety of recurrent infections. We present a case of chronic diarrhea in a patient with a history of resected thymoma many years prior to presenta- tion. We briefly discuss the pathogenesis, presenta- tion, and treatment of GS. CASE PRESENTATION A 50-year-old gentleman was evaluated for chronic diarrhea with duration of eight years. He reported having 8-15 loose stools every day along with unintentional weight loss of 100 pounds in the last year. He reported that stools were loose in consistency accompanied by abdominal cramps. There was no history of blood in stools. Diarrhea would wake him up from sleep, and he experienced diarrhea despite fasting. His past medical history was significant for incidental thymoma (status post thymectomy about 10 years ago). Extensive labo- ratory workup to rule out infectious etiology, fat malabsorption, celiac disease, and inflammatory bowel disease was negative. Colonoscopic exam was normal with random right- and left-sided bi- opsies showing mild focal active colitis; terminal ileum was normal. Trial of steroids and oral mesala- mine failed to improve symptoms. After multidisci- plinary evaluation considering history of thymoma and chronic diarrhea, we suspected GS. Serum quantitative immunoglobulins were found to be extremely low: IgG 55 mg/dL, IgA <25 mg/dL, IgM <17 (references values: 700-1600 mg/dL, 70-400 mg/dL, and 40-230 mg/dL respectively). Upon flow cytometry, B-cells were undetectable (<1% of total lymphocytes). These findings confirmed the diag- nosis of GS. Patient was initiated on treatment with monthly Intravenous Immunoglobulin (IVIG). He ex- perienced significant improvement of diarrhea over the following few weeks (1-2 formed stools/day) and had a 24-pound weight gain in two months. DISCUSSION Good’s syndrome is a rare cause of combined immunodeficiency seen in adults and is character- ized by a triad of thymoma, immunodeficiency, and hypogammaglobulinemia. This acquired immuno- deficiency usually manifests in late adulthood and affects both cell-mediated and humoral immune system. Immunodeficiency in these patients puts them at risk of recurrent sino-pulmonary infections and many opportunistic viral, bacterial, and fungal infections. The first case was reported by Rob- ert Good in 1954. 1 Around 3-6% of patients with thymoma have concomitant hypogammaglobu- linemia. 2,3 GS usually manifests in the 40- to 50- year age group, with equal predominance in males and females. Although GS can present in children, it is very rare. According to the systematic review of more than 150 patients on Good syndrome, the incidence of GS in highest in the Europe. 4 The pathogenesis of GS is heterogeneous. The primary immunologic abnormalities in this disease are hypogammaglobulinemia, reduced number of B cells, and CD4+ T lymphocytes. 4 Hypogamma- globulinemia was found in 100% of patients with GS across two reviews. A hypothesis suggests that certain cytokines arrest or impair B-cell matura- tion, leading to the above defects. 5 Abnormalities in CD4+:CD8+ T cell ratio are also commonly seen, and many of these patients have cutaneous anergy to two or more test antigens. Good’s syn- 260 • THE JOURNAL OF THE ARKANSAS MEDICAL SOCIETY drome is also commonly associated with anemia, leukopenia, and thrombocytopenia. Some mani- festations, like pure red-cell aplasia (PRCA) seen in GS suggest an autoimmune component in either etiology or pathogenesis of the disease. 6 The initial presentation of GS can be varied. In many patients, the diagnosis of thymoma is usu- ally preceded by recurrent infections with intervals of months to years. Thymoma is a slow-growing neoplasm presenting as a mediastinal mass. It can be a benign tumor or a malignant tumor that is capable of distant metastasis. Due to the location of tumor, it can present with respiratory symptoms including cough, dyspnea, hoarseness, chest pain, dysphagia, or compression symptoms including superior vena cava syndrome or Horner’s syndrome. In some patients, it can be totally as- ymptomatic and found only incidentally. As these patients have defects in both cellular and humoral immunity, they are susceptible to a variety of re- current infections. The most common bacterial infections reported in these patients is recurrent sino-pulmonary infections, especially with encap- sulated organisms. 7 Hemophilus influenza (24%), pseudomonas (22%) and Klebsiella (13.2%) are the three most common organisms isolated. 4 Bacteremia, urinary tract infections, and bacterial diarrhea are the other common bacterial infec- tions. Other infections reported include mycobac- terial infections; viral infections with CMV, VZV, HSV, JC, HHV-8 and HPV; and fungal infections with Candida, Aspergillus, and Pneumocystis jiroveci. 4 Though uncommon, parasitic infections were also reported in these patients. It is important to note that chronic diarrhea is the presenting symptom in 50% of patients, as was the case in the patient we are reporting. While infectious etiology is the most common cause of diarrhea, malabsorption secondary to villous atrophy or immune-mediated colitis has also been reported. Salmonella, clos- tridium, Giardia, and CMV are a few organisms as- sociated with diarrhea in these patients. However, in many patients, a definitive organism was not VOLUME 115