Disseminated tuberculosis presenting as cutaneous leucocytoclastic vasculitis
- Abhishek Verma ,
- Sunita Aggarwal ,
- Ranvijay Singh and
- Tushar Mittal
- Medicine, Maulana Azad Medical College, New Delhi, Delhi, India
- Correspondence to Professor Sunita Aggarwal; drsunita.mamc@gmail.com
Abstract
Cutaneous leucocytoclastic vasculitis (CLV) is a type of small vessel vasculitis, predominantly presenting with palpable purpuras and sometimes with systemic manifestations. The following report describes the case of a woman, who presented with fever, anorexia and maculopapular lesions over both lower limbs. Skin biopsy revealed CLV. CT scan demonstrated bilateral pulmonary nodules, ileocecal wall thickening and generalised lymphadenopathy. Colonoscopy guided biopsy obtained from ileocecal valve ulcer showed epitheloid cell granuloma with Langhans-type giant cells and caseous necrosis. Rapid clinical improvement was seen with anti-tubercular therapy. Among infectious causes, although rare and an uncommon presentation, Mycobacterium tuberculosis should be considered as an important cause of CLV.
Background
Tuberculosis (TB) is one of the most prevalent communicable infectious diseases. TB is known to affect different body tissues with variable clinical manifestations, and among them TB-related vasculitis is one of the rare presentations. Vasculitis can affect blood vessels of all sizes, resulting in multisystemic involvement with a variety of signs and symptoms. It can be classified into large vessel, medium vessel and small vessel vasculitis, depending on the type of vessel affected. Cutaneous leucocytoclastic vasculitis (CLV) is a small vessel vasculitis that majorly involves dermal postcapillary venules.1 It can be idiopathic or secondary to systemic vasculitis disorders, autoimmune diseases, neoplasm, drug hypersensitivity and infections. Among infectious causes, TB is a rare one. Here, we present the case of a woman, who initially presented with CLV, and after extensive workup, was found to be having disseminated TB as an underlying aetiology. This case demonstrates this rare association between TB and CLV.
Case presentation
A woman in her early 20s presented with complaints of fever for 20 days. It was insidious in onset and of low grade. It was associated with fatigue, malaise, anorexia and relieved on taking paracetamol. Eight days later, she developed discrete erythematous maculopapular eruptions of size varying from 0.1×0.1 cm to 1×1 cm over bilateral legs and feet. Eruptions were painless, non-blanchable and non-pruritic. She was having a dry cough for 10 days. She did not have any other localising symptoms or chronic illness. She had regular menstrual cycles. She was not taking any other drugs. No history of any kind of substance abuse and contact with pulmonary TB case. She was vaccinated with BCG at birth. On examination, she had pallor, mild bilateral pitting type pedal oedema. Rest of the systemic examination was unremarkable.
Investigations
She underwent multiple investigations to identify the underlying disease. She had microcytic hypochromic anaemia with haemoglobin 64g/L and reticulocyte production index of 0.5. Total leucocyte and platelet count were normal. She had hypoproteinaemia with serum protein 4.7 g/dL and serum albumin 2.2 g/dL. Rest of her liver and kidney function tests was normal. The erythrocyte sedimentation rate (78 mm/hour) was raised. Her ferritin level (243 mcg/L) was raised, serum iron level (42 mcg/dL) was low, vitamin B12 and folic acid levels were normal. Urine routine examination was normal. Skin biopsy was obtained from rashes and it was suggestive of the presence of leucocytoclastic vasculitis (figure 1). She had elevated levels of rheumatoid factor and C reactive protein. Anti-streptolysin O titre was <200 tu/mL. Further, titres of antinuclear antibody, anti-dsDNA antibody and anti neutrophilic cytoplasmic antibody (ANCA) were in a normal range. Serum cryoglobulin levels were normal. Serology for HIV-1 and HIV-2, hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) antibody, dengue virus and rickettsia was negative. Further, no organism was isolated on blood and urine cultures. CT scan of neck, chest, abdomen and pelvis was done. It showed the presence of lymphadenopathy in retropharyngeal, right supraclavicular, mediastinal, mesenteric and retroperitoneal region, along with nodular opacities in bilateral upper lung lobes and circumferential wall thickening involving ileocecal region (figure 2). On Mantoux tuberculin skin test, she had horizontal induration of 14 mm (more than 10 mm is significant, in view of resident of TB endemic country). On colonoscopy, ileocecal valve was deformed and patulous with superficial lip showing a large superficial ulcer covered with whitish exudates. On inferior lip, a 5 mm×5 mm nodule was seen covered with erosions. Biopsy obtained from these lesions showed focal denudation along with distortion of crypt architecture in the form of crypt dilatation and crypt loss. Lamina propria shows multiple coalescent epitheloid cell granulomas with Langhans-type giant cells and caseous necrosis along with dense lymphoplasmacytic infiltrate in the background (figure 3). This confirmed the diagnosis of disseminated TB (pulmonary, abdominal and lymph node) along with secondary CLV.
H&E stained skin biopsy showing features consistent with leucocytoclastic vasculitis.
CT image of abdomen showing circumferential thickening of ileal loop (marked with solid black arrow).
H&E stained biopsy of ileocecal valve lesions (40× image on left, 100× image on right) showing epitheloid cell granulomas with Langhans-type giant cells and caseous necrosis along with dense lymphoplasmacytic infiltrate in the background.
Treatment
After confirmation of the presence of TB, the patient was started on anti-tubercular therapy (isoniazid/rifampicin/pyrazinamide/ethambutol for 2 months followed by isoniazid/rifampicin/ethambutol for 4 months) with pyridoxine. Steroids were not prescribed during the course of therapy.
Outcome and follow-up
With therapy, she started showing clinical improvement with resolution of fever over the next 7 days, improvement in apatite in 10 days and followed by resolution of rashes over 3 weeks. She was able to attend her college back and resume her studies by second week of therapy. She completed 6 months of anti-tubercular therapy, uneventfully, with complete recovery.
Discussion
CLV is a type of small vessel vasculitis, with predominant cutaneous manifestations due to the involvement of dermal postcapillary venules. It most commonly presents with palpable purpura, however, may also present with macules, papules, vesicles, nodules, ulcers or urticaria. Skin lesions may be painful or pruritic sometimes. These lesions are most commonly seen in lower limbs, because of hydrostatic forces on postcapillary venules. It can be primary (idiopathic) or secondary to drugs, infections, malignancy, primary vasculitis, autoimmune and connective tissue disorders.2
Diagnosis of CLV is confirmed on tissue biopsy. Histopathologically, it is identified by the presence of inflammation with leucocytoclasia (neutrophilic fragmentation), fibrinoid necrosis and neutrophilic infiltrates around blood vessel walls along with extravasation of erythrocytes. The absence of tubercular bacilli in biopsy specimens in CLV differentiates it from cutaneous TB.3 The next step in management is to identify the aetiology followed by treating that underlying cause. In cases of persistent vasculitis, where no underlying cause is identified, dapsone, hydroxychloroquine, non-steroidal anti-inflammatory drugs and glucocorticoids have been tried with some success, as reported in previous studies.4
Among infectious causes, TB is a rare one. In previous literature, TB is reported with three forms of vasculitis—Henoch–Schonlein purpura, vasculitis secondary to rifampicin and CLV. The exact pathogenesis of CLV secondary to TB is still not known completely. Multiple possible explanations have been proposed, including deposition of immune complexes, arthus reaction in response to bacilli, direct invasion of bacilli in vessels, delayed-type hypersensitivity reaction and association with anti-tubercular drugs (especially seen with rifampicin).2 5
In this case, confirmation of vasculitis and TB on biopsy and clinical improvement with anti-tubercular therapy is supportive of the association between TB and CLV. Our patient acquired TB, in spite of receiving BCG vaccine. BCG vaccine has a protective efficacy of 0%–80% against tubercular meningitis and disseminated TB. Our case is evidence for a causal association between these two pathological entities. However, further studies and trials are needed to identify the pathogenesis behind this association.
This case demonstrates TB causing CLV. TB is a rare aetiology for CLV, still, a highly prevalent disease, especially in developing countries. Thus, treating physicians should be aware of this association, so that, tubercular therapy can be initiated early to attain uneventful recovery in a maximum number of such patients.
Patient’s perspective
It all started with a simple fever and later when I developed rashes, I visited hospital for check-up. Initially, I was not giving so much attention to this. But, later, when multiple investigations were not able to identify my disease, I started feeling low and was worried, if I am having some unknown and uncurable disease. I was not able to focus on my studies. My treating doctors explained me the need for further imaging and tests, for which I agreed. With CT scan report, cancer was the first and only thing in my mind. After undergoing colonoscopy and guided biopsy, my doctor informed me about tuberculosis. It was ultimately a great relief for me, knowing, my disease is diagnosed and that too is treatable. I completed my drug therapy after 6 months, uneventfully.
Learning points
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Cutaneous leucocytoclastic vasculitis (CLV) is a small vessel vasculitis, which can be primary or secondary to other systemic diseases.
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Tuberculosis (TB) is a great masquerade and can present with various atypical manifestations also.
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TB is a rare but treatable cause of CLV. It should be kept in mind as a possible aetiology while evaluating cases of vasculitis.
Ethics statements
Patient consent for publication
Footnotes
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Contributors Supervised by SA. Patient was under the care of SA, AV, RS and TM. AV, RS and TM were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms and critical revision for important intellectual content. SA and AV gave the final approval of the manuscript. Is the patient one of the authors of this manuscript? No.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.
References
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