Case Report

J Med Discov (2020); 5(1):jmd19030; DOI:10.24262/jmd.5.1.19030; 
Received August 30th, 2019, Revised January 30th, 2020, Accepted February 23rd, 2020, Published March 22nd, 2020.

ANCA glomerulonephritis in a patient with active tuberculosis

Noor M. Mualla¹, Rizwan Badar², Bashar Al hemyari², Jyotsna Sharma²

¹Icahn School of Medicine at Mount Sinai, The Mount Sinai Hospital, New York, NY 10029.

²University of California Riverside School of Medicine, GME Office, Riverside, CA 92501

* Correspondence:Noor M. Mualla, Icahn School of Medicine at Mount Sinai, The Mount Sinai Hospital, New York, NY 10029. Email: noor.mualla@icahn.mssm.edu

TANCA vasculitis is a necrotizing vasculitis that commonly affects the medium and small vessels. Characterized by necrotizing granulomatous inflammation and the presence of anti neutrophil cytoplasmic antibodies (ANCA). However, tuberculosis may sometimes lead to elevation of serum ANCA titers, making it hard to diagnose and should always rule out ANCA vasculitis in the differential diagnosis, to ensure fast response within a short period of time. Here we presented a case manifested initially with symptoms suggestive with active tuberculosis, remission noted within appropriate treatment. However worsening renal failure findings and serum ANCA positive titers, suggest actual ANCA vasculitis, which confirmed by renal biopsy.

Keywords: ANCA, Tuberculosis, Glomerulonephritis, ANCA vasculitis

ANCA associated vasculitis is a type of autoimmune disease that causes necrotizing vasculitis, usually affects the medium and small arteries. It can be associated with ANCA specific for myeloperoxidase (MPO-ANCA/P-ANCA) or proteinase 3 (PR3-ANCA/C-ANCA). Symptoms depend on what organ has been involved. When ANCA vasculitis involves the kidney, these ANCA antibodies attack small blood vessels in the glomeruli and damage it. ANCA glomerulonephritis is the term used when ANCA vasculitis has involved the kidney.
Major variants of ANCA associated vasculitis include Microscopic polyangiitis, Granulomatosis with polyangiitis (Wegener’s), and Eosinophilic granulomatosis with polyangiitis (Churg- Strauss). However, some infectious diseases, such as bacterial endocarditis and tuberculosis may sometimes show high titers of ANCA, mimicking vasculitis. Tuberculosis is an infection caused by Mycobacterium tuberculosis and is believed to induce the development of antibodies such as positive (ANCA) that can be indicators for the diagnosis of other diseases. Based on reports, conflicting results found on tuberculosis patients with a positive ANCA.

A 77-year-old Guatemalan male with no known past medical history, presented with dyspnea and dry cough for 4 weeks. CXR and CT chest revealed fibrosis, nodules and a small cavitary lesion in the upper lobe. BAL confirmed active pulmonary TB with positive acid-fast bacilli stain. Patient was started on Anti-tuberculosis (TB) drugs. However, his creatinine began to worsen from 2.3mg/dl on admission to 4.6mg/dl. Multiple urinalysis revealed microscopic hematuria. He had 5 grams of proteinuria based on protein to creatinine ratio. Workup for AKL was unrevealing. P-ANCA was elevated to 1:640 (normal, <3.5 U/mL). Renal biopsy was performed, and revealed active chronic pauci-immune crescentic glomerulonephritis.

Figure 1: see proliferation of cells occupying the entire Bowman’s space (green arrows) and compressing the tuft (red arrows). The blue arrows indicate the Bowman’s capsule. This is the characteristic aspect of an epithelial crescent, in this case circumferential. Cells forming the crescent may be epithelial, monocytes or other inflammatory cells. (Masson’s trichrome, X400).

Figure 1 cites:  Mualla, N. M. (n.d.). Bowman’s space. photograph, LA.

Figure 2: This immunofluorescence micrograph of a glomerulus demonstrates positivity with antibody to fibrinogen. With a rapidly progressive GN, the glomerular damage is so severe that fibrinogen leaks into Bowman’s space, leading to proliferation of the epithelial cells and formation of the bright crescent shown.

Figure 2 cites: Mualla, N. M. (n.d.). Immunofluorescence micrograph of a glomerulus. photograph, LA.

From our search of the literature, we found only one other case of ANCA glomerulonephritis in a patient with active tuberculosis.

There are many reported cases in the literature of patients with tuberculosis who had positive ANCA titers, but none had actual ANCA vasculitis. However, in this case, remission of TB was noted after initiating the anti TB treatments, while the ANCA titer remained high, with worsening creatinine level and renal failure findings, all indicating the presence of actual ANCA vasculitis.

We can not be certain if our patient had two unrelated disease processes, or if the elevated ANCA titers as seen in other cases of tuberculosis, actually lead to an ANCA vasculitis in our patient. The other uncertainty is whether or not tuberculosis can actually predispose patients to ANCA vasculitis.

Of note, the management is difficult for these patients as immunosuppression could potentially worsen the outcome of a patient with active tuberculosis.

The etiology underlying remains unclear. The most common etiology was “anti-TB drug-induced vasculitis”.

Based on previous case reports showing various anti- TB drugs have been reported as causative agents for vasculitis, such as propylthiouracil (PTU), isoniazid (INH) and rifampicin. These agents might interrupt the resolution of the neutrophil extracellular trap, acting as the mechanism behind vasculitis. The other explaining etiology is that secondary elevation of ANCA induced by a chronic inflammation by TB infection lead to development of vasculitis.

While the patient was receiving treatment for TB, we instituted 60mg prednisone daily. Once repeat BAL was negative for acid-fast bacilli, we then added weekly Rituximab infusions. By his third dose, his creatinine had decreased to 2.8mg/dl and proteinuria had decreased to 3.2 grams. Unfortunately due to the patient’s financial constraints he was later lost to follow up.

None

None

1. Huan, Gao, Yang, Gao, Xiao-yu, Qu, Jiancheng, Xu, & Yan-qing, Song. (2018). Antineutrophil cytoplasmic antibodies in Chinese patients with tuberculosis. Revista da Sociedade Brasileira de Medicina Tropical, 51(4), 475-478. https://dx.doi.org/10.1590/0037-8682-0400-2017
2. Iijima, Yuki MD a,*; Kobayashi, Yoichi MD a; Uchida, Yoshinori MD a; Tsutsui, Toshiharu MD, PhD a; Kakizaki, Yumiko MD a; Naganuma, Tsukasa MD b; Tsukamoto, Katsuhiko MD c; Oyama, Toshio MD d; Miyashita, Yoshihiro MD a Medicine. 97(43):e12430, October 2018.
3. Guiyi Ji, Xuemei Zeng, Andrew J. Sandford, and Jian-Qing He.Rifampicin-induced antineutrophil cytoplasmic antibody-positive vasculitis: a case report and review of the literature. 2016; 54: 804-807. doi: 10.5414/CP202576.
4. Yamauchi K, Sata M, Machiya J, et al. Antineutrophil cytoplasmic antibody positive alveolar haemorrhage during propylthiouracil therapy for hyperthyroidism. Respirology 2003;8:532–5.
5. Culver B, Itkin A, Pischel K. Case report and review of minocycline- induced cutaneous polyarteritis nodosa. Arthritis Rheum 2005;53: 468–70.
   [17]  Tan CD, Smith A, Rodriguez ER. Systemic necrotizing vasculitis induced by isoniazid. Cardiovasc Pathol 2014;23:181–2.
6. Kim JH, Moon JI, Kim JE, et al. Cutaneous leukocytoclastic vasculitis due to anti-tuberculosis medications, rifampin and pyrazinamide. Allergy Asthma Immunol Res 2010;2:55–8.
7. Jordan D. Rosen, Olivera Stojadinovic, Jeffrey D. McBride, Rene Rico, Jeong Hee Cho-Vega and Anna J. Nichols, Bowel-associated dermatosis-arthritis syndrome (BADAS) in a patient with cystic fibrosis, JAAD Case Reports, 10.1016/j.jdcr.2018.08.029, 5, 1, (37-39), (2019).
8. Middleton, D. Karp, E. Lee, J. Cush Wegener’s granulomatosis presenting as lower back pain with prostatitis and ureteral obstruction J Rheumatol, 21 (1994), pp. 566-569.

© This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/