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.
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].
Respiratoric
Sputum
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]
On the second day of hospitalization, induced sputum was positive for Pneumocystis jiroveci and Moraxella catarrhalis. [link.springer.com]
Case presentation We present a case of a 75-year-old caucasian male patient with recurrent emergency visits in 2007, with prolonged febrile illness, recurring infections, anorexia, weight loss ( 18 Kg in 3 months), cough with muco-purulent sputum and [casesjournal.biomedcentral.com]
Sputum smear revealed no pathogens, apart from Candida albicans, and microbiological examination of sputum and blood was negative. [cimonline.ca]
Subsequent sputum culture revealed growth of Pseudomonas aeruginosa and Candida albicans. Screening for HIV and CMV IgM was negative. [revportpneumol.org]
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]
Left eye examination revealed mild anterior uveitis, moderate vitritis, and superotemporal active retinitis. Polymerase chain reaction of both aqueous humor and vitreous tap were positive for CMV DNA, which suggested CMV retinitis. [ncbi.nlm.nih.gov]
In patients with uveitis and CMVR, Behcet's disease and anterior uveitis comprised two cases each (28.5 %), followed by one case each (14.3 %) of anterior uveitis, Vogt-Koyangi-Harada disease, idiopathic posterior uveitis, and idiopathic panuveitis. [joii-journal.springeropen.com]
Face, Head & Neck
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]
Neurologic
Polyoma virus JC, the agent of progressive multifocal encephalopathy (PML), was identified in cerebrospinal fluid samples and brain biopsy specimens. After diagnosis, the disease had a rapid fatal course. [ncbi.nlm.nih.gov]
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]
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]
This patient showed cutaneous anergy, even though he had normal numbers of peripheral blood total lymphocytes as well as CD4 and CD8 T cells. [jimmunol.org]
Studies of cell mediated immunity in Good's syndrome emphasised that T cell defects, as manifested by cutaneous anergy to two or more test antigens, 32, 33 or delayed rejection of skin allografts, 28, 34 were common features of this condition. [jcp.bmj.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]
mediastinal mass on chest x ray. [jcp.bmj.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]
Human Herpesvirus 8
Moreover, CMV retinitis, mucocutaneous candidiasis, herpes simplex virus (HSV) and human herpesvirus 8 (HHV-8) infections have been described. In rare cases, central nervous system (CNS) infection may be seen. [symptoma.com]
In particular, cytomegalovirus (CMV) colitis and retinitis and mucocutaneous candida infection are prominent features of this condition. 6 Opportunistic infection caused by herpes simplex, 12 human herpesvirus 8, 13 varicella zoster, 8 and Pneumocystis [jcp.bmj.com]
Mycoplasma hominis septic arthritis has a well-established association with hypogammaglobulinaemia, but is rarely seen in immunocompetent hosts. An association also exists with a closed trauma and a predisposition to M hominis bone infections. [ncbi.nlm.nih.gov]
Multiple Ulcerations
Persistent diarrhea followed by colonic bleeding due to multiple ulcers and a severe liver dysfunction seemed to bring him to his death. [ncbi.nlm.nih.gov]
Despite meningeal involvement our patient recovered after combined treatment with intravenous globulin, granulocyte stimulating growth, corticosteroids and antifungal therapy. [ncbi.nlm.nih.gov]
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]
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]
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 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]
Autoreactive T cells in patients may form as a consequence of exposure of neoepitopes, altered antigen processing allowing pathogenic epitopes to be presented, or altered T-cell regulation. [12] Etiology Like other autoimmune conditions, anti-GBM disease [emedicine.medscape.com]
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]
[…] exposure include the following: Exposure to organic solvents or hydrocarbons Smoking Infection (eg, influenza A2) Cocaine inhalation Exposure to metal dusts Lymphocyte-depletion therapy, such as alemtuzumab Extracorporeal shock wave lithotripsy [14] Epidemiology [emedicine.medscape.com]
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]
Pathophysiology Anti-GBM disease is an autoimmune disorder characterized by autoantibodies directed against the glomerular/alveolar basement membrane. [emedicine.medscape.com]
CRUSH PATHOPHYSIOLOGY Our patient had many injuries. I do not intend examining all of these, but will highlight Crush Injury with references to Compartment Syndrome and Rhabdomyolysis. [medenosrce.net]
The pathophysiology of pure red cell aplasia: implications for therapy. Blood 1996 ; 87 : 4831 –8. Litwin SD, Zanjani ED. Lymphocyte suppressing both immunoglobulin and erythroid differentiation in hypogammaglobulinaemia. Nature 1977 ; 266 : 57 –8. [jcp.bmj.com]
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]
Kelleher P, Misbah SA. What is Good's syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003;56(1):12-16.
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.
Tachdjian R, Keller JJ, Pfeffer M. A Bad Case of Good's Syndrome. Infect Dis Ther. 2014;3(2):333-337.
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.
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.
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.
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.