Presentation
However, in the case of the NEMO defect, anhidrotic ectodermal dysplasia is also present. [medicover-genetics.com]
The atypical mucosal presentation had already prompted a suspicion of an underlying immunodeficiency at the time of initial presentation (11). [frontiersin.org]
In the present study, we report a case of X-linked HIGM with a new CD40L gene mutation (HIGM1) presenting with eosinophilia in a young Chinese boy. [spandidos-publications.com]
So although the problem presents as an inability of B cells to make an appropriate antibody response to infections, the defect is on T cells. [dermnetnz.org]
Individuals with Down syndrome are known to have abnormal function of the B-cell function, which might present with high IgG and low IgM serum level. [adc.bmj.com]
Entire Body System
- Anemia
[…] potentially fatal liver disease called sclerosing cholangitis Neutropenia, a low white blood cell count often associated with oral ulcers and skin infections Other symptoms of HIgM syndrome may include: Development of autoimmune disorders, including hemolytic anemia [chop.edu]
Another patient with the same variant (p.Arg11∗) has been described by (33); the patient was a previously completely healthy 8-year-old boy who presented with anemia, which was later recognized as parvovirus B19 induced anemia. [frontiersin.org]
Both presented with Parvovirus B19 infections, the major clinical manifestation of which was anemia in 1 and anemia and neutropenia in the other 52. FIGURE 4: Age at onset of symptoms in patients with the X-linked hyper-IgM syndrome. [journals.lww.com]
Their manifestations may include chronic arthritis, low platelet counts (thrombocytopenia), hemolytic anemia, hypothyroidism and kidney disease. [primaryimmune.org]
Some patients with a milder form of the disease, present in adolescence with a Parvovirus-induced aplastic anemia. [cancertherapyadvisor.com]
- Recurrent Infection
People with hyper IgM syndromes may develop recurrent infections, severe infections, and, in some cases, opportunistic infections. Some forms have defects in their T cells, in addition to an antibody deficiency. [columbiadoctors.org]
Clinically, these patients present with recurrent infections secondary to immunodeficiency (due to impaired humoral immunity), with significant lymphoid hyperplasia. [pixorize.com]
Recurrent infection is the hallmark of all immunodeficiency diseases. Recurrent sinopulmonary infections are seen in antibody deficiency diseases as well as in the combined (Tcell and antibody) immune deficiencies. [cancertherapyadvisor.com]
"Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome". Gastroenterology. 94 (3): 808–12. [wikidoc.org]
Patients with Hyper-IgM (HIGM) syndrome are susceptible to recurrent and severe infections and in some types of HIGM syndrome opportunistic infections and an increased risk of cancer as well. [primaryimmune.org]
- Recurrent Bacterial Infection
Patients with these syndromes typically have recurrent bacterial infections and often have lymphoid hyperplasia. [genome.jp]
Infections Pneumonia was the most common infection, followed by sinusitis, recurrent otitis, and recurrent/protracted diarrhea. [journals.lww.com]
- Recurrent Respiratory Infection
Clinically, these patients present with recurrent infections secondary to immunodeficiency (due to impaired humoral immunity), with significant lymphoid hyperplasia. [pixorize.com]
respiratory infections, or an opportunistic infection, a doctor might screen for HIGM. [myigsource.com]
The most common problem in all forms of HIGM syndrome is an increased susceptibility to infection including recurrent upper and lower respiratory tract infections. [primaryimmune.org]
Musculoskeletal
- Arthritis
[…] white blood cell count often associated with oral ulcers and skin infections Other symptoms of HIgM syndrome may include: Development of autoimmune disorders, including hemolytic anemia and/or thrombocytopenia (abnormally low platelet counts) Chronic arthritis [chop.edu]
Other autoimmune conditions can develop including inflammation of the liver (hepatitis), and in rare cases, inflammatory bowel syndrome and arthritis. [rarediseases.org]
[…] common and is present in over 70% of healthy people's lungs, however, Hyper IgM patients are not able to fight it off without the administration of Bactrim[medical citation needed] Hepatitis (Hepatitis C) Chronic diarrhea Hypothyroidism Neutropenia Arthritis [en.wikipedia.org]
Their manifestations may include chronic arthritis, low platelet counts (thrombocytopenia), hemolytic anemia, hypothyroidism and kidney disease. [primaryimmune.org]
[…] anti-erythropoietin, anti-platelet, anti-smooth muscle, anti-cardiolipin, anti-Ro, anti-RNP, anti-nuclear and anti-thyroid).6,7 Other autoimmune manifestations seen in HIGM patients include inflammatory bowel disease, autoimmune hepatitis, seronegative arthritis [nature.com]
- Osteoporosis
Management of osteoporosis in primary biliary cirrhosis. Baillieres Best Pract Res Clin Gastroenterol 2000; 14: 629–641. CAS Article Google Scholar 18 Invernizzi P, Lleo A, Podda M. [nature.com]
Workup
Rheumatologic workup revealed positive ANA (1:160) and positive dsDNA (1:40). Antibodies for SS-A (Ro), SS-B(La), and SCL-70 were negative. Infectious disease workup was positive for treponemal antibody and elevated RPR (1:2). [karger.com]
Clinical Testing and Workup Blood tests will be ordered to determine the status of immunoglobulins in the blood, including normal or high levels of IgM and low levels of other immunoglobulin classes. [rarediseases.org]
Serum
- Hypogammaglobulinemia
CVID is characterized by B cell dysfunction, which results in hypogammaglobulinemia and diminished vaccine responses. Different versions of diagnostic criteria for CVID have been used (2–4). [frontiersin.org]
Females with hypogammaglobulinemia and high IgM levels should be tested for gene mutations that affect other forms of HIGM. Age Most patients are diagnosed before age 4 years. [emedicine.medscape.com]
The diagnosis of X-linked hyper IgM (XHIM) syndrome should be considered in any boy presenting with hypogammaglobulinemia, characterized by low or absent IgG and IgA and normal or elevated IgM levels. [medigoo.com]
"Increased susceptibility to Mycoplasma infection in patients with hypogammaglobulinemia". Am. J. Med. 80 (4): 590–4. PMID 3963038. ↑ Yong PF, Thaventhiran JE, Grimbacher B (2011). [wikidoc.org]
Thus, in addition to their hypogammaglobulinemia, patients with CD40L deficiency have defective antigen-induced T-cell proliferation 2 and defective T-cell effector function 25. [journals.lww.com]
Treatment
The treatments can be administered either at home or in an outpatient clinic. IVIG is the only effective treatment for ARHIM. Other treatments include: Antibiotics: Boys with XHIM are often given antibiotics to prevent certain types of pneumonia. [childrens.com]
However, G-CSF treatment is only necessary in selected patients and long-term treatment with G-CSF is usually not recommended. [primaryimmune.org]
Gene therapy is also being investigated as a potential treatment for individuals with hyper IgM syndromes. More studies are needed and it’s still too early to tell if gene therapy could offer a viable treatment alternative. [chop.edu]
Treatment Following treatment of intravenous immunoglobulin (IVIG), trimethoprim-sulfamethoxazole and glucocorticoid agents, the pulmonary infection was significantly reduced. [spandidos-publications.com]
Prognosis
The other forms of autosomal recessive hyper IgM (caused by mutations in AID and UNG) have a better prognosis as the defect is mainly an antibody deficiency. [cancertherapyadvisor.com]
Because of the poor prognosis, the treatment of choice is a human leukocyte antigen (HLA)-identical sibling bone marrow transplant at an early age (62,63). Treatment for this condition also includes monthly IVIG infusions (64). [lvts.fr]
While a permanent cure is anticipated after successful stem cell transplantation, the long-term prognosis for these patients is not yet known. [primaryimmune.org]
Although earlier diagnosis and the availability of more effective therapies, including those for opportunistic infections, may improve the prognosis of patients with XHIGM, their prognosis is still guarded. [journals.lww.com]
Etiology
TABLE 3: Etiology of Pneumonia TABLE 4: Etiology of Diarrhea TABLE 5: Etiology of Sepsis TABLE 6: Etiology of CNS Infection TABLE 7: Etiology of Hepatitis and Sclerosing Cholangitis Pneumonia Over half of the patients who had experienced pneumonia had [journals.lww.com]
Ongoing controversies regarding etiology, diagnosis, treatment [cancertherapyadvisor.com]
Patient 1 has cerebellar ataxia of unknown etiology despite intensive investigation. [jci.org]
Infectious agents and xenobiotics in the etiology of primary biliary cirrhosis. Dis Markers 2010; 29: 287–299. Article Google Scholar 28 Abdulkarim AS, Petrovic LM, Kim WR, Angulo P, Lloyd RV, Lindor KD. [nature.com]
Epidemiology
Holman RCJanssen RSBuehler JWZelasky MTHooper WC Epidemiology of progressive multifocal leukoencephalopathy in the United States: analysis of national mortality and AIDS surveillance data. Neurology 1991;411733- 1736PubMedGoogle ScholarCrossref 13. [jamanetwork.com]
Epidemiology Frequency United States In 2003, the US XHIGM registry reported that the minimal incidence rate of XHIGM was approximately 1 in 1,000,000 live births from 1984-1993. [4] This may be an underestimation because not all physicians in the United [emedicine.medscape.com]
Pathophysiology
Immunology: Clinical Case Studies and Disease Pathophysiology. John Wiley & Sons. ISBN 9781118966006. Retrieved 27 November 2016. Kleinman, Ronald (2008). Walker's Pediatric Gastrointestinal Disease. PMPH-USA. ISBN 9781550093643. [en.wikipedia.org]
Pathophysiology IgM is the form of antibody that all B cells produce initially, before they undergo class switching due to exposure to a recognized antigen. [wikidoc.org]
[…] for X-linked hyper-IgM (XL-HIGM) or CD40L deficiency, primarily in male patients younger than 10 years of age Ascertaining XL-HIGM carrier status in females of child-bearing age younger than 45 years of age Clinical Information Discusses physiology, pathophysiology [mayocliniclabs.com]
Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies. Adv Immunol. 2007. 94:275-306. [Medline]. Eijkhout HW, van Der Meer JW, Kallenberg CG, et al. [emedicine.medscape.com]
Prevention
So a mutation that mostly affects T cells, prevents these T cells from “helping” B cells and therefore looks like a B cell problem. [hyperigm.org]
Antibody replacement can prevent infections and reduce mortality and morbidity, but cannot prevent cancer and other severe complications. [cancertherapyadvisor.com]
Children receiving this treatment get regular infusions of donated blood plasma to prevent infections. In boys with XHIM, IVIG replaces missing IgG antibodies while normalizing levels of IgM. [childrens.com]
[…] therapy to prevent infections and treat autoimmune complications (administered by direct infusion [IVIG] or just below the surface of the skin [subcutaneous immunoglobulin]) Restricted contact to avoid exposure to new potential infections An allogeneic [chop.edu]
However it may not prevent the opportunistic infections. In some cases it also improves growth. Trimethoprim + sulphamethoxazole may be given prophylactically to prevent Pneumocystis jirovecii infection. [dermnetnz.org]