• Users Online: 695
  • Home
  • Print this page
  • Email this page

 Table of Contents  
Year : 2016  |  Volume : 5  |  Issue : 1  |  Page : 106-110

Selective immunoglobulin M deficiency in an adult with miliary tuberculosis: A clinically interesting coexistence. A case report and review of the literature

1 Department of Internal Medicine, Faculty of Medicine, Sohag University Hospital, Sohag, Egypt
2 Department of Internal Medicine, Hematology Division, Faculty of Medicine, Sohag University Hospital, Sohag, Egypt

Date of Web Publication8-Feb-2017

Correspondence Address:
Hassan A Hassanein
Department of Internal Medicine, Sohag Faculty of Medicine, Sohag University, Sohag 82524
Mahmoud I Elbadry
Department of Internal Medicine, Hematology Division, Faculty of Medicine, Sohag University Hospital
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.1016/j.ijmyco.2015.11.002

Rights and Permissions

Selective immunoglobulin M (SIgM) deficiency is a rare form of dysgammaglobulinemia. Here we are reporting a 31 year old man with multiple cervical and testicular abscesses who was investigated and found to have miliary tuberculosis (MTB) with primary SIgM deficiency (Serum IgM: 17.4 mg/dL) and was treated aggressively with anti-tuberculous treatment.

Keywords: Selective IgM deficiency, Primary immunodeficiency, Unusual infections, Miliary tuberculosis

How to cite this article:
Hassanein HA, Elbadry MI. Selective immunoglobulin M deficiency in an adult with miliary tuberculosis: A clinically interesting coexistence. A case report and review of the literature. Int J Mycobacteriol 2016;5:106-10

How to cite this URL:
Hassanein HA, Elbadry MI. Selective immunoglobulin M deficiency in an adult with miliary tuberculosis: A clinically interesting coexistence. A case report and review of the literature. Int J Mycobacteriol [serial online] 2016 [cited 2023 Mar 31];5:106-10. Available from: https://www.ijmyco.org/text.asp?2016/5/1/106/199736

  Case report Top

A 31-year-old previously healthy man with an unremarkable clinical history presented with predominant symptoms of fatigue fevers, chills, malaise, anorexia and weight loss 1 year duration. 3 months later, the patient developed painful scrotal swelling on the left side of the scrotum which was drained by a doctor associated with greenish foul discharge and patient was empirically started on broad-spectrum intravenous (IV) antibiotics. The patient was admitted to the Fever Hospital in February 2015 for evaluation of history fever and recurrent scrotal swellings, he was found to have multiple testicular abscesses, which were treated with multiple courses of antibiotics. Despite the medical treatment, the patient had another painful swelling on the right side of the neck, so he was subsequently referred to our hospital in April 2015 as a case of recurrent mucocutaneous abscess formation in order to create a diagnosis and treatment plan. He did not have any significant past medical history or surgical history or any risk factors for HIV. There was no history of childhood infections, relatives with opportunistic infections or immunodeficiencies.

Physical examination of the patient on admission was normal except his body temperature was ranging between 38.2 and 39.4 °C and pallor. Cystic tender swelling (4×3cm) was located in the subclavian triangle area, in the supraclavicular region expanding to the occipital triangle. The skin over the swelling was lividly discolored with signs of necrosis associated with generalized small lymphadenopathy. There was scrotal sinus on the left side of the scrotum with signs of necrosis.

At that moment, laboratory tests revealed normal blood sugar, urine analysis and serum biochemistry except mild hypoalbuminemia, mild elevation in liver enzymes and ESR 70 mm/h. There were no abnormalities in WBCs and platelets count except mild lymphocytopenia and microcytic anemia. Serum iron, ferritin were within normal limits.

In routine work up chest X-ray revealed radiologic evidence of MTB and this was confirmed with a positive culture for acid alcohol fast bacilli from a laryngeal swab and blood culture revealed Mycobacterium tuberculosis. The BCG scar was present and normal, with negative results of tuberculin test. Neck U/S revealed a bilocular cystic lesion each of them about 2.5×3cm with markedly turbid fluid content. Pus is seen at lower deep cervical to suprasternal notch with multiple enlarged variable size lymph nodes with no abnormal vascularity. Abdominal U/S was normal except mild hepatomegaly. Scrotal U/S and Doppler revealed an abscess about (3×1cm) at the left scrotal neck with hypo echoic area about (3×1cm) is seen at the parenchyma of the testis and another abscess about (5×3cm) is seen at the left thigh (intra muscular). Rt testis showed multiple hypoechoic focal lesions. Screening for malignancy revealed negative results for testicular tumors such as alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), lactate dehydrogenase (LDH). Serological viral studies revealed negative results of HIV, hepatitis C virus antibodies and hepatitis B surface antigen. Most clinically relevant autoantibodies were checked, but all of them were found to be negative. Laboratory work-up of immunodeficiency was performed ([Table 1]). The blood cell count, T cells, T cell subsets, B cells, and natural killer cells were within normal limits. Also, we examined the performance of delayed-type hypersensitivity (DTH) antigens using a tetanus toxoid. Our patient was of middle aged. Therefore, our patient is unlikely to have a partial deficiency of adenosine deaminase (ADA). Therefore, no ADA analysis was performed. Interferon У secretion and IFN-УR expression could not be done due to financial causes.
Table 1: Laboratory findings on admission.

Click here to view

Once the diagnosis of symptomatic sIgMD with miliary tuberculosis was recognized, the patient was treated aggressively with the courses of Isoniazide, Rifampicin, Pyrazinamide, Ethambutol and Clarithromycine to covering for disseminated TB or severe atypical mycobacterial infection. He showed dramatic improvement after antimycobacterial therapy and the patient was discharged after 1month of hospitalization on Isoniazide, Rifampicin and Pyrazinamide. Subsequently, chest X-ray normalized. But sputum smears still positive for AFB after 4 months of treatments. Within 5 months, most of patient symptoms disappeared and scrotal, Abdominal and neck U/S normalized and sputum smears for AFB became negative.

  Discussion Top

SIgM deficiency is a rare form of dysgammaglobulinemia which was described first in 2 children with fulminant meningococcal septicemia, more than 45 years ago [1] and characterized by an isolated low level of serum immunoglobulin M (IgM). There have been a few cases reported in the literature, with a reported prevalence of 0.03–3% [2],[3],[4]. Adults with primary sIgM deficiency usually associated with autoimmune diseases and malignant neoplasm [3],[4] whereas children may present with severe life-threatening infections, a few cases of possible primary sIgM deficiency in adults with no evidence of autoimmunity or malignant neoplasm have been reported [5]. Adult patients usually present with mild infections. Our patient, who was previously healthy with no evidence of autoimmunity or neoplasm, represents a possible case of primary sIgM deficiency in adults with severe life-threatening and unusual infections (Miliary tuberculosis). We reviewed and compared previously reported 43 patients with sIgMID from 1967 to 2015, including our patient, and their characteristics are summarized in [Table 2].
Table 2: Summary of reported cases with selective IgM deficiency.

Click here to view

IgM provides the initial response to foreign antigen and plays a regulatory role in the subsequent immune response development, accelerating the production of high-affinity IgG [6]. SIgM deficiency can be asymptomatic or may symptomatically present with infections from encapsulated bacteria and viruses, some of which can be serious and even life threatening infections varying from pneumonia to septicemia and meningitis. A few cases of sIgMD with mycobacterium avium complex (MAC) infection or M. tuberculosis, but none of them presented with MTB without T-cell disorders [7].

In primary sIgM deficiency, B cells, T cells and T cell subsets, and NK cells are normal [2],[8]. T cell functions are normal [2]. Innate immune functions are normal [2]. Specific antibody response to pneumococci is impaired in 50% of symptomatic cases [2] as in our case. However, several patients with selective IgM deficiency and T cell and NK cell defects with MAC intracellulare infections have been reported [7]. In a subset of patients with sIgM deficiency circulating IgM+B cells are decreased or completely lacking. Specific IgG antibody responses against pneumococcus polysaccharides are impaired in a subset of patients with selective IgM deficiency who appear to respond to immunoglobulin therapy [6]. Furthermore, immunologic investigation neglected any possibility of an immune defect associated with tuberculosis, In our case the innate immunity is intact. T cells, T cell subsets, and T cell functions and phagocytic responses, serum IgA, IgE, IgG, and IgG subclasses were normal. The presence of the BCG scar as well as normal lymphocyte blastogenesis ruled out SCID.

Several studies have previously reported and classified IgM deficiency in primary or secondary type. Our patient had no history of autoimmune disease or malignancy, as demonstrated in secondary IgM deficiency, so primary IgM deficiency was suggested. Is there any possibility of direct relationship between occurrence of secondary IgM deficiency and MTB? So, after 5 months of treatment with negative results of sputum smears for AFB, we reinvestigated the serum level of IgM, which was low (22 mg/dL) and serum IgG, IgA, and IgE were normal (1153, 233.2, 42 mg/dL respectively) with a normal lymphocyte count. After an extensive literature review, we found relationship between lymphopenia and MTB. Lymphopenia improved after starting antituberculosis treatment [9]. However, they could not come up with a direct relationship between the cause of IgM deficiency and tuberculosis. Gerasimos, et al. reported an HIV-seronegative adult with disseminated TB having marked T-lymphocytopenia, which normalized after treatment with anti-tuberculosis therapy. Lymphocytopenia was attributed to disseminated TB [10]. There is no obvious explanation for the cause of T cell depletion. Probabilities include consumption at the site of infection, such as the lungs or suppression of T cell production by the MTB. Certain components of MTB such as D-arabino-D-galactan activate suppressor mechanism in vitro, which in turn might cause lymphocyte depletion [10] and IgM deficiency as a part of immune system suppression. It may be the observation of a phenomenon that need to be supported by conducting a cohort study of patients with MTB by analyzing lymphocyte subsets and IgM deficiency in a prospective manner.

In contrast, the pathogenesis of primary sIgM deficiency is unknown with no specific genetic or molecular basis defined. A number of defects have been reported, including intrinsic B cell defects in plasma cell differentiation [8], increased T cell suppressor activity, which may be specific to IgM isotype or isotype-nonspecific [5]. There is no report of formation of anti-IgM antibodies (anti IgA occur in 20–40% of sIgA deficiency). Furthermore, transformation to panhypogammaglobulinemia or common variable immunodeficiency has not been reported for sIgMID, although subclass IgG deficiencies can occur [8]. This suggests that sIgM deficiency is a heterogeneous disorder, which requires further studies to elucidate the predominant mechanisms involved in its pathogenesis.

Although a role of antibodies in defense against MTB has not been described in detail, there is some evidence for the role of B cells and antibodies in host defense against intracellular pathogens including M. tuberculosis, as B cells can regulate both CD4+ and CD8+ T cell memory responses and produce antibodies and cytokines which can modulate the maturation of antigen-presenting cells. Also B cells can regulate the differentiation of macrophages into subsets which are important in anti-mycobacterial defense. While role of antibodies are evident in the presence of monoclonal antibodies specific for a number of mycobacterial components including arabinomannan, lipoarabinomannan, heparin-binding hemagglutinin, and 16kD-crystalin, and passive transfer of serum with polyclonal antibodies against M. tuberculosis is protective in relapse of tuberculosis in SCID mice and the role is also supported by M. tuberculosis infections in patients with X-linked agammaglobulinemia. Ultimately, a role of antibodies in mycobacterial defense is supported by the presence of IgG antibodies against glycopeptidolipid (GPL) core antigen of MAC in 77% of patients with pulmonary MAC and none in pulmonary tuberculosis [11]. Therefore, an antibody defect in our patient may be responsible for the development of MTB. Further examination using lymphocytes of the patient with sIgMD will be necessary to establish the pathogenesis of this disease.

  Conclusion Top

Miliary tuberculosis without T-cell disorders in a healthy adult should lead to further investigation of underlying diseases including primary immunodeficiencies.

Conflict of interest statement

The authors have no conflicts of interest to declare.

  References Top

J.R. Hobbs, R.D. Milner, P.J. Watt, Gamma-M deficiency predisposing to meningococcal septicaemia, Br. Med. J. 4 (1967) 583–586.  Back to cited text no. 1
L. Yel, S. Ramanuja, S. Gupta, Clinical and immunological features in IgM deficiency, Int. Arch. Allergy Immunol. 150 (2009) 291–298.  Back to cited text no. 2
T. Takeuchi, T. Nakagawa, Y. Maeda, S. Hirano, M. Sasaki- Hayashi, S. Makino, A. Shimizu, Functional defect of B lymphocytes in a patient with selective IgM deficiency associated with systemic lupus erythematosus, Autoimmunity 34 (2001) 115–122.  Back to cited text no. 3
S. Saini, A.J. Dettore, K.J. Bhambhani, S. Buck, J. Poulik, S. Savaşan, IgM deficiency in CD30+ cutaneous lymphoproliferative disorder, J. Pediatr. Hematol. Oncol. 33 (2011) 156–159.  Back to cited text no. 4
T. Ohno, M. Inaba, K. Kuribayashi, Selective IgM deficiency in adults: phenotypically and functionally altered profiles of peripheral blood lymphocytes, Clin. Exp. Immunol. 68 (1987) 630–637.  Back to cited text no. 5
A.G. Louis, S. Gupta, Primary selective IgM deficiency: an ignored immunodeficiency, Clin. Rev. Allergy Immunol. 46 (2014) 104–111.  Back to cited text no. 6
Sudhir Gupta, Sudhanshu Agrawal, Sastry Gollapudi, Selective IgM deficiency with T cell defects and Mycobacterium avium complex (MAC) infection, Open Immunol. J. 5 (2012) 8– 12.  Back to cited text no. 7
M.F. Goldstein, A.L. Goldstein, E.H. Dunsky, D.J. Dvorin, G.A. Belecanech, K. Shamir, Selective IgM deficiency: retrospective analysis of 36 adult patients with review of the literature, Ann. Allergy Asthma Immunol. 97 (2006) 717–730.  Back to cited text no. 8
E.N. Gonc, S. Ozen, A. Gocmen, Y. Zafer, I. Tezcan, Severe lymphopenia in tuberculosis. A mere coincidence or a significant association?, Turk J. Pediatr. 42 (2000) 65–67.  Back to cited text no. 9
G.J. Zaharatos, M.A. Behr, M.D. Libman, Profound Tlymphocytopenia and cryptococcemia in a human immunodeficiency virus-seronegative patient with disseminated tuberculosis, Clin. Infect. Dis. 33 (2001) 125–128.  Back to cited text no. 10
Asal Gharib, Ankmalika Gupta Louis, Sudhanshu Agrawal, Sudhir Gupta, Syndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous Mycobacterium avium intracellulaire infection, Am. J. Clin. Exp. Immunol. 4 (2015) 15–27.  Back to cited text no. 11


  [Table 1], [Table 2]

This article has been cited by
1 Unbalanced serum immunoglobulins in clinical subtypes of pediatric tuberculosis disease
Filippo Consonni, Nicolň Chiti, Silvia Ricci, Elisabetta Venturini, Clementina Canessa, Leila Bianchi, Francesca Lippi, Carlotta Montagnani, Mattia Giovannini, Elena Chiappini, Luisa Galli, Chiara Azzari, Lorenzo Lodi
Frontiers in Pediatrics. 2022; 10
[Pubmed] | [DOI]
2 Green Method Synthesised Graphene-Silver Electrochemical Nanobiosensors for Ethambutol and Pyrazinamide
Rachel Fanelwa AjayI,Siphokazi Tshoko,Yonela Mgwili,Siphamandla Nqunqa,Takalani Mulaudzi,Noluthando Mayedwa,Emmanuel Iwuoha
Processes. 2020; 8(7): 879
[Pubmed] | [DOI]
3 Selective immunoglobulin M deficiency: An underestimated immunodeficiency disorder – not so rare
Arun Agarwal
Indian Journal of Allergy, Asthma and Immunology. 2020; 34(1): 43
[Pubmed] | [DOI]
4 Expected advantage of urine lipoarabinomannan for tuberculosis detection in human immunodeficiency virus-endemic setting
Beuy Joob,Viroj Wiwanitkit
International Journal of Mycobacteriology. 2019; 8(4): 413
[Pubmed] | [DOI]
5 Challenges in investigating patients with isolated decreased serum IgM: The SIMcal study
Lisanne M. A. Janssen,Roeland W. N. M. Hout,Esther de Vries,Claudio Pignata,Emilia Cirillo,Peter D. Arkwright,Vassilos Lougaris,Matthew Buckland,Marina Garcia-Prat,Vall dćHebron,Pere Soler-Palacin,Monia Ouederni,Pavlina Kralickova,Hassan Abolhassani,Lennart Hammerstrom,Asghar Aghamohamamdi,Juan L. Santos-Pérez,Ali Sobh,Jutte van de Werff ten Bosch,Stefanie Henriet,Sara S. Kilic,Y. Karali,Luis Ignacio Gonzalez-Granado,Anna Sediva
Scandinavian Journal of Immunology. 2019; : e12763
[Pubmed] | [DOI]
6 Autoimmunity and immunodeficiency at the crossroad: autoimmune disorders as the presenting feature of selective IgM deficiency
Corrado Campochiaro,Sirin Atay,Kristina E N Clark,Voon Ong,Christopher P Denton
BMJ Case Reports. 2019; 12(1): e223180
[Pubmed] | [DOI]
7 Selective IgM Deficiency: Clinical and Laboratory Features of 17 Patients and a Review of the Literature
Zita Chovancova,Pavlina Kralickova,Alena Pejchalova,Marketa Bloomfield,Jana Nechvatalova,Marcela Vlkova,Jiri Litzman
Journal of Clinical Immunology. 2017;
[Pubmed] | [DOI]
8 Truly selective primary IgM deficiency is probably very rare
L. M. A. Janssen,T. Macken,M. C. W. Creemers,J. F. M. Pruijt,J. J. J. Eijk,E. de Vries
Clinical & Experimental Immunology. 2017;
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case report
Article Tables

 Article Access Statistics
    PDF Downloaded154    
    Comments [Add]    
    Cited by others 8    

Recommend this journal