Edit concept Question Editor Create issue ticket

Good's Syndrome

Good Syndrome

Good's syndrome is a very rare form of adult-onset primary immunodeficiency in which the development of thymoma and recurrent infections involving various systems cause significant morbidity and mortality. The diagnosis rests on the identification of hypogammaglobulinemia and other associated laboratory findings and the prognosis strongly depends on a timely diagnosis.


Presentation

The clinical presentation of Good's syndrome (GS) starts during adulthood, most commonly in the 4th or 5th decade of life, with a mean survival rate of 14 years and overall mortality rates of 45-57% according to most recent reports [1] [2]. Recurrent infections due to bacterial, viral and fungal pathogens are the most important manifestation of Good's syndrome, arising due to extensive hypogammaglobulinemia and lymphopenia of varying severity [3] [4]. Most notable examples are infections of the sinuses and the respiratory tract by encapsulated bacteria (haemophilus influenzae and streptococcus pneumoniae, as well as klebsiella pneumoniae and pseudomonas aeruginosa) and fungi (pneumocystis jirovecii), cutaneous and urinary tract infections, but also diarrheas caused by giardia lamblia, campylobacter jejuni, cytomegalovirus (CMV) and salmonella spp. [5] [6] [7]. Moreover, CMV retinitis, mucocutaneous candidiasis, herpes simplex virus (HSV) and human herpesvirus 8 (HHV-8) infections have been described [1]. In rare cases, central nervous system (CNS) infection may be seen [7]. Sinorespiratory infections manifest with a cough, nasal discharge, fever, and headaches, while diarrhea, abdominal pain, cramping and weight loss are typical signs of gastrointestinal infection. The second cardinal feature of Good's syndrome is the presence of a thymoma, and up to 42% of patients have a confirmed diagnosis prior to the onset of infections [3]. In addition, thymomas are associated with a number of autoimmune disorders, and up to 50% of patients present with signs and symptoms of myasthenia gravis, whereas pemphigus, sjögren syndrome, pure red cell aplasia (PRCA) and systemic lupus erythematosus (SLE) have all been identified in patients suffering from this type of immunodeficiency [4]. In up to 10% of patients, hypogammaglobulinemia may be quite severe even after successful removal of thymomas and is the main cause of mortality in this patient group [3].

Nasal Discharge
  • Sinorespiratory infections manifest with a cough, nasal discharge, fever, and headaches, while diarrhea, abdominal pain, cramping and weight loss are typical signs of gastrointestinal infection.[symptoma.com]
Anterior Uveitis
  • Left eye examination revealed mild anterior uveitis, moderate vitritis, and superotemporal active retinitis. RESULTS: Polymerase chain reaction of both aqueous humor and vitreous tap were positive for CMV DNA, which suggested CMV retinitis.[ncbi.nlm.nih.gov]
Neck Mass
  • A 34-year-old male with a right palpable neck mass had been mistakenly diagnosed with T-cell lymphoblastic lymphoma even after an open biopsy.[ncbi.nlm.nih.gov]
Meningism
  • Despite meningeal involvement our patient recovered after combined treatment with intravenous globulin, granulocyte stimulating growth, corticosteroids and antifungal therapy.[ncbi.nlm.nih.gov]
  • […] commonly affect the upper and lower respiratory tracts (eg, sinopulmonary infections, including chronic otitis media, sinusitis, bronchitis/bronchiectasis, pneumonia ), gastrointestinal tract (eg, bacterial or parasitic gastroenteritis), skin, joints, and meninges[emedicine.medscape.com]
Aphasia
  • However, 1 week after admission, motor aphasia and mild right hemiparesis reappeared. MRI showed that the lesion involving the left cingulate gyrus expanded in size, and revealed an abnormal signal intensity lesion in the left corona radiata.[ncbi.nlm.nih.gov]

Workup

Despite the fact that less than 200 patients have been diagnosed with GS so far [4], an early diagnosis must be achieved in order to reduce the risk of adverse events and prevent more serious infections that can be life-threatening [3]. For this reason, a detailed patient history (including assessment of age) must be obtained in order to identify the recent development of symptoms that may suggest recurrent infections, but laboratory studies are essential during diagnostic workup. A complete blood count (CBC) is mandatory and should be obtained right away, with anemia, leukopenia (either granulocytopenia or lymphopenia) and/or thrombocytopenia being frequently observed [7]. Furthermore, a thorough immunological workup composed of CD4+/CD8+ T cell and B cell counts and a quantitative immunoglobulin assessment will confirm lymphopenia and hypogammaglobulinemia [3]. Because many patients suffer from additional immunological diseases, detection of anti-acetylcholine receptor (AChR) antibodies, anti-Ro/SSA and anti-La/SSB, as well as antinuclear antibodies (ANA) for myasthenia gravis, sjögren syndrome and SLE, respectively, should be performed. Bone marrow aspiration, as a last resort, can reveal markedly reduced hematopoiesis [6]. On the other hand, the presence of recurrent infections should raise valid suspicion toward disorders of the thymus, and imaging studies, mainly in the form of computed tomography (CT), but also biopsy, are necessary to identify thymoma as an accompanying feature and thus confirm the diagnosis.

Anergy
  • There was cutaneous anergy to intra dermal antigen challenge.Flow cytometry revealed reduced mature circulating B cells,reduced CD4 count and reversal of CD4:CD8 ratio.Bone marrow biopsy showed reduced pre-B cell lineage.Patient has remained stable on[neurology.org]
  • The main abnormalities are an increase in circulating naive T cells, cutaneous T-cell anergy, TCR hyporesponsiveness in vitro as well as a numerical and functional impairment of regulatory T cells.[dl.begellhouse.com]
Anterior Mediastinal Mass
  • Imaging and laboratory studies revealed a large anterior mediastinal mass and panhypoimmunoglobulinemia, respectively. A biopsy was consistent with thymoma, and a diagnosis of Good's syndrome was established.[ncbi.nlm.nih.gov]
  • Chest CAT disclosed a left sided infiltrate with a loculated pleural effusion(Figure 1,A), as well as an anterior mediastinal mass(Figure 1,B).[shmabstracts.com]
  • Initial investigations revealed an anterior mediastinal mass, which was excised with biopsy confirming the diagnosis of thymoma. The patient then presented to our hospital in May 2011.[jpma.org.pk]
Bilateral Pulmonary Infiltrate
  • Abstract A 61-year-old woman who had undergone an operation for thymoma 17 years previously suddenly became dyspneic and showed bilateral pulmonary infiltrates on a chest radiograph.[ncbi.nlm.nih.gov]
  • The patient received a total of four days of immunoglobulin therapy but despite treatment the patients' condition worsened with the development of bilateral pulmonary infiltrates and severe sepsis (Figure-2).[jpma.org.pk]
Mycoplasma Hominis
  • Author information 1 Department of Internal Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA. [email protected] Abstract Mycoplasma hominis septic arthritis has a well-established association with hypogammaglobulinaemia, but is rarely[ncbi.nlm.nih.gov]

Treatment

  • SCF production was reduced in bone marrow stromal cells; however, it was restored in vitro and in vivo after cyclosporine-A treatment. [Indexed for MEDLINE] Free full text[ncbi.nlm.nih.gov]
  • The patient was treated with systemic treatment of acyclovir and ganciclovir combined with weekly intravitreal injections of ganciclovir and foscarnet. Retinitis resolved within 3 weeks and visual acuity improved.[ncbi.nlm.nih.gov]
  • A 40-year-old man presented with sputum-positive PTB and was started on anti-tuberculosis treatment. Subsequently, he developed symptoms and findings consistent with thymoma and other components of Good's syndrome.[ncbi.nlm.nih.gov]
  • Its prompt treatment is crucial. [Indexed for MEDLINE] Free full text[ncbi.nlm.nih.gov]
  • Abstract A 63-year-old man was admitted to our hospital for treatment of hypogammaglobulinemia with thymoma (Good's syndrome).[ncbi.nlm.nih.gov]

Prognosis

  • This rare condition should not be misdiagnosed, as the prognosis is determined by infectious and autoimmune complications, which could be prevented.[ncbi.nlm.nih.gov]
  • Good's syndrome remains a rare entity often associated with poor prognosis. Adequate surgical resection remains key to outcomes, whereas immunotherapy aids in reducing postoperative complications and may improve survival.[ncbi.nlm.nih.gov]
  • CONCLUSIONS: GS is a rare association of thymoma and immunodeficiency with a poor prognosis.[ncbi.nlm.nih.gov]
  • The diagnosis rests on the identification of hypogammaglobulinemia and other associated laboratory findings and the prognosis strongly depends on a timely diagnosis.[symptoma.com]
  • CONCLUSIONS GS is a rare association of thymoma and immunodeficiency with a poor prognosis.[unboundmedicine.com]

Etiology

  • We further studied the etiology of this case. A burst-forming unit erythroid (BFU-E) assay with SCF restored erythropoiesis in vitro.[ncbi.nlm.nih.gov]
  • The etiologic relationship between thymoma and acquired hypogammaglobulinemia remains unclear. Thymectomy is generally ineffective in improving immunologic deficiencies and coexisting conditions in patients with acquired hypogammaglobulinemia.[ncbi.nlm.nih.gov]
  • "The significance of certain pulmonary lesions in relation to the etiology of influenza". Am J Med Sci . 158 (6): 863–870. doi : 10.1097/00000441-191911000-00012 . Salama AD, Levy JB, Lightstone L, Pusey CD (September 2001). "Goodpasture's disease".[en.wikipedia.org]
  • However, genetic analysis has begun to elucidate the etiology of Good’s syndrome, which, like CVID, appears to affect proteins involved in the proliferation and differentiation of B cells [ 9 , 10 ].[link.springer.com]
  • B and T cell immunodysregulation in thymoma patients is sometimes referred to as GS [ 4 , 20 ], but it represents rather a different disease with distinct etiology and pathogenesis where B cell lymphopenia due to differentiation arrest seems to be crucial[omicsonline.org]

Epidemiology

  • Conclusions Epidemiological studies have repeatedly helped identify definitive triggers for several diseases.[medworm.com]
  • […] demonstrated that in patients requiring renal replacement therapy (including dialysis) the median survival time is 5.93 years. [6] Without treatment, virtually every affected person will end up dying from either advanced kidney failure or lung hemorrhages. [6] Epidemiology[en.wikipedia.org]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology [ edit ] GPS causes the abnormal production of anti-GBM antibodies, by the plasma cells of the blood. [6] The anti-GBM antibodies attack the alveoli and glomeruli basement membranes. [6] These antibodies bind their reactive epitopes to[en.wikipedia.org]

Prevention

  • This rare condition should not be misdiagnosed, as the prognosis is determined by infectious and autoimmune complications, which could be prevented.[ncbi.nlm.nih.gov]
  • Infection has been prevented for one year after beginning IVIG replacement therapy.[ncbi.nlm.nih.gov]
  • Astute clinical acumen and increased awareness about the clinical and immunological profile of this syndrome may increase early recognition of this syndrome and prevent mortality. Further studies are needed to elucidate this clinical entity.[ncbi.nlm.nih.gov]
  • Despite the fact that less than 200 patients have been diagnosed with GS so far, an early diagnosis must be achieved in order to reduce the risk of adverse events and prevent more serious infections that can be life-threatening.[symptoma.com]
  • Medications taken when you get a transplant also help to prevent your body's immune system from making the harmful antibodies. Is research being done on Goodpasture's Syndrome? Yes.[kidney.org]

References

Article

  1. Kelleher P, Misbah SA. What is Good’s syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003;56(1):12-16.
  2. Jansen A, van Deuren M, Miller J, et al. Prognosis of Good syndrome: mortality and morbidity of thymoma associated immunodeficiency in perspective. Clin Immunol. 2016;171:12-17.
  3. Tachdjian R, Keller JJ, Pfeffer M. A Bad Case of Good’s Syndrome. Infect Dis Ther. 2014;3(2):333-337.
  4. Malphettes M, Gérard L, Galicier L, et al. Good syndrome: an adult-onset immunodeficiency remarkable for its high incidence of invasive infections and autoimmune complications. Clin Infect Dis. 2015;61(2):e13-19.
  5. Sun X, Shi J, Wang M, Xu K, Xiao Y. Good’s Syndrome Patients Hospitalized for Infections: A Single-Center Retrospective Study. Callens. S, ed. Medicine (Baltimore). 2015;94(47):e2090.
  6. Agarwal S, Cunningham-Rundles C. Thymoma and immunodeficiency (Good syndrome): a report of 2 unusual cases and review of the literature. Ann Allergy Asthma Immunol. 2007;98(2):185-190.
  7. Ueno S, Sekimoto-Tsuboi S, Ishiguro Y, et al. Good’s syndrome with opportunistic infection of the central nervous system: a case report. BMC Neurol. 2015;15:150.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2018-06-22 10:30