Pulmonary Mycobacterium tuberculosis Associated ...

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temperature of 38.1˚C. Patient had generalized petechia without mucocutaneous bleeding. Mild cervical and supraclavicular lymphadenopathy was present.

Pulmonary Mycobacterium tuberculosis Associated Immune Thrombocytopenia Purpura Harish R. Patlolla MD.1 Andrew C. Miller MD 2,3 1 Department of Medicine, Mount Sinai Hospital. Chicago, IL. 2 Critical Care Medicine Department, National Institutes of Health Clinical Center. Bethesda, MD. 3 Department of Emergency Medicine, West Virginia University. Morgantown, WV. Introduction


Table 1

Table 2

Immune thrombocytopenia purpura (ITP) secondary to pulmonary Mycobacterium tuberculosis (MTB) infection is a rare condition whose course differs from that of conventional ITP. We report the case of a 29-year-old man who presented with complaints of gingival bleeding and hematuria. He was diagnosed with ITP secondary to MTB infection, which responded to 4-drug direct observed treatment (DOT) with isoniazid, rifampin, pyrazinamide, and ethambutol (with pyridoxine).

Figure 2. Lymph node biopsy. Hematoxylin and eosin (H&E) stain. High-power field (50X magnification). The illustrated caseating TB granuloma is characterized by a central area of necrotic material (long black arrow) surrounded by an outer layer of macrophages, elongated epithelioid cell precursors, aka histiocytes (short white arrow), multinucleated giant cells (long white arrow), and ringed by T-lymphocytes (short black arrow).

Case Description A 29-year-old man presented with gingival bleeding, hematuria, and a petechial rash. He reported a 24-pound weight loss, weakness, abdominal discomfort, lowerextremity paresthesias, night-sweats, and shortness-ofbreath. Recent HIV testing was negative. He denied sick contacts, Mycobacterium tuberculosis (MTB) exposure, incarceration, or military experience.

Figure 1. Admission Chest X-ray illustrating an ill-defined opacity obscuring the superior aspect of the right hilum and a less well-defined density obscuring the left hilum.

Figure 3. Wedge biopsy (Left Upper Lobe Lung) revealed acid-fast bacilli.

Immune thrombocytopenia purpura (ITP) treatment was initiated with intravenous (IV) corticosteroids and IV immune globulin (IVIG). Bone marrow biopsy was performed (Table 2). Subsequent mediastinoscopy with lymph node biopsy was complicated by massive hemothorax. Emergent thoracotomy achieved hemostasis, and intra-operative left upper-lobe biopsy was obtained. Scalene lymph node biopsy yielded necrotizing granulomata (Figure 2), and wedge biopsy revealed acidfast bacilli (Figure 3). He was treated with isoniazid, rifampin, pyrazinamide, and ethambutol for MTB. He remains clinically improved and without recurrent thrombocytopenia at 1 year.

Thrombocytopenia results from impaired production, sequestration, or decreased platelet survival. Production defects generally involve multiple cell lineages and arise from marrow failure from toxins, infiltration, aplasia, sepsis, or infections (rubella, CMV, EBV, parvovirus, and varicella). Conversely, thrombocytopenias resulting from consumption or increased destruction may be distinguished into immune- or non-immune-mediated. Immune-mediated forms include ITP, drugs, posttransfusion, systemic lupus erythematosis (SLE), lymphoproliferative disorders, chronic infections (HIV, HCV, Helicobacter pylori) and heparin-induced thrombocytopenia (HIT). Non-immune-mediated processes include vascular prostheses, disseminated intravascular coagulation (DIC), thrombotic thrombocytopenia purpura/hemolytic uremic syndrome (TTP/HUS), HELLP syndrome, and eclampsia. MTB may present with various hematologic abnormalities including anemia, leukocytosis/-penia, thrombocytosis/-penia, monocytosis, lymphopenia, leukemoid reactions, and pancytopenia. ITP is a rare but described presentation.


Exam was significant for heart rate of 116/min, and temperature of 38.1˚C. Patient had generalized petechia without mucocutaneous bleeding. Mild cervical and supraclavicular lymphadenopathy was present. Lungs fields were clear, heart sounds normal, and no hepatosplenomegaly was evident. Pertinent laboratory values are listed in Table 1. Notably, patient demonstrated severe thrombocytopenia, HIVnegative CD4-lymphopenia, and anemia consistent with chronic inflammation. Peripheral smear revealed absence of platelets and normal cell morphology. Coagulation studies were normal. Chest X-ray revealed ill-defined bilateral hilar opacities (Figure 1). Chest CT identified diffuse ill-defined parenchymal and sub-pleural opacities, and bilateral supraclavicular and mediastinal lymphadenopathy.


CT Chest Imaging

Figure 4. Bone Marrow Biopsy displayed hyper cellular marrow (cellularity 65%), myeloid:erythroid ratio 3:1, tri-lineage maturation, normal morphology, and increased megakaryocytes. No granulomata, lymphoma, or fibrosis was seen. Acid-fast and fungal stains were negative.

Immune thrombocytopenia purpura (ITP) secondary to pulmonary Mycobacterium tuberculosis (ITP/MTB) infection is a rare but described condition whose course differs from that of conventional ITP. ITP typically requires long-standing corticosteroids, often relapses, and may require splenectomy for long-term remission. Conversely, ITP/MTB responds to short-duration corticosteroids followed by anti-tuberculosis therapy without relapse. Of the 16 cases reported, 0 and 1 patients had a known history of MTB or ITP respectively. In each case, thrombocytopenia resolved with MTB treatment. In patients presenting with ITP, lymphadenopathy, and pulmonary infiltrates, underlying MTB should be considered. Lymph node or lung biopsy should be considered to confirm the diagnosis if sputum AFB is negative, as an MTB diagnosis carries important therapeutic and social implications.

References 1. Ozkalemkas F, Ali R, Ozkan A, et al. Tuberculosis presenting as immune thrombocytopenic purpura. Ann Clin Microbiol Antimicrob. 2004;3:16. 2. Talbot S, Dowling A, Dowling JP, et al. Mediastinal nodal tuberculosis presenting as immune thrombocytopenia. Aust N Z J Med. 1998;28(4):465-466. 3. Tsuro K, Kojima H, Mitoro A, Yoshiji H, Fujimoto M, Uemura M, Masahide Y,Fukui H. Immune thrombocytopenic purpura associated with pulmonary tuberculosis. Intern Med. 2006;45(11):739-42. 4. Spedini P. Tuberculosis presenting as immune thrombocytopenic purpura. Haematologica. 2002;87(2):ELT09.