|Year : 2021 | Volume
| Issue : 3 | Page : 330-334
Concomitant disseminated tuberculosis and lepromatous leprosy in a previously healthy male
Baldeep Kaur1, Daljinderjit Kaur1, Monica Gupta1, Nandini Agrawal2, Sarabmeet Singh Lehl1
1 Department of General Medicine, Government Medical College and Hospital, Sector 32, Chandigarh, India
2 Department of Pathology, Government Medical College and Hospital, Sector 32, Chandigarh, India
|Date of Submission||19-Feb-2021|
|Date of Acceptance||07-Mar-2021|
|Date of Web Publication||03-Sep-2021|
Department of General Medicine, Level 4 D Block, Government Medical College and Hospital, Chandigarh - 160 030
Source of Support: None, Conflict of Interest: None
Tuberculosis (TB) and leprosy are two chronic mycobacterial infections caused by intracellular Gram-positive aerobic acid-fast bacilli. Both have highly variable presentations depending on immunological milieu of the host and account for significant disease morbidity. The burden of these age-old infections of humanity still remains high in India. Regardless of the same geographical endemicity of the two, coinfections are sparsely reported. Indeed, studies have revealed an antagonism between them. Of the few coinfections reported in the past, majority were diagnosed over a temporal sequence, with one occurring after the other, and most of these were localized forms of TB associated with leprosy. Only a single case of disseminated TB and lepromatous leprosy has been reported in the medical literature till date. Here, we report another rare case of disseminated TB and lepromatous leprosy that ultimately proved fatal for the patient. The diagnosis of the two diseases was made simultaneously which is again infrequent in the reported literature.
Keywords: Coinfection, leprosy, tuberculosis
|How to cite this article:|
Kaur B, Kaur D, Gupta M, Agrawal N, Lehl SS. Concomitant disseminated tuberculosis and lepromatous leprosy in a previously healthy male. Int J Mycobacteriol 2021;10:330-4
|How to cite this URL:|
Kaur B, Kaur D, Gupta M, Agrawal N, Lehl SS. Concomitant disseminated tuberculosis and lepromatous leprosy in a previously healthy male. Int J Mycobacteriol [serial online] 2021 [cited 2021 Dec 3];10:330-4. Available from: https://www.ijmyco.org/text.asp?2021/10/3/330/325504
| Introduction|| |
Tuberculosis (TB) and leprosy are two of the most physically and psychosocially devastating diseases known to affect human health. TB accounted for 10 million new cases in 2017, with India harboring more than 25% of the global TB incidence. Likewise, the annual leprosy incidence was more than 200,000 globally, with India, Brazil, and Indonesia accounting for more than 80% of all the cases in the world. Both of them manifest with a bipolar spectrum of clinical features and histopathology that depend upon individual's immune response to the infective agent. The continuum of TB ranges from the anergic, multibacillary forms (miliary and periorificial) on one pole and the hyperergic, paucibacillary forms (lupus vulgaris and verrucous TB) on the other. A similar polarization is observed in leprosy ranging from paucibacillary tuberculoid leprosy to multibacillary lepromatous leprosy and the intermediate forms: borderline tuberculoid, mid-borderline, and borderline lepromatous in between the two poles. The conversion of both tuberculin and lepromin intradermal tests after the Bacillus Calmette–Guerin (BCG) vaccine for TB suggests evidence of a similar antigen profile. Prevalence of both these diseases individually is common in community in economically underprivileged nations, but concurrence in an individual is a sporadic entity. Despite literature showing evidence in favor and against, the exact correlation between TB and leprosy still remains ambiguous. Chaussinand concluded that the prevalence of leprosy varied inversely with the prevalence of TB. The transmission dynamics of two infections, with TB having higher reproductive rate and greater degree of infectivity than leprosy, does not allow both infections to occur simultaneously. On the other hand, Kumar et al. report that TB exists all through the spectrum of leprosy refuting the theory of cross-immunity. Here, we present the case of a middle-aged male simultaneously diagnosed with lepromatous leprosy and disseminated TB during the hospital admission.
| Case Report|| |
A 41-year-old male, a daily wager, presented to the emergency room with fever, pain abdomen, and vomiting of 7-day duration. He also complained of cough, shortness of breath, and bilateral lower-limb swelling over the past 1 month. In addition, there were an undocumented weight loss, loss of appetite, and generalized weakness. He also gave a history of 2–3 episodes of mild epistaxis that resolved on their own. There was no past history suggestive of nodular or painful skin lesions, joint pains, eye complaints, or neuritis. His past history was unrevealing of diabetes mellitus, hypertension, or TB. The patient was a reformed alcoholic and a chronic smoker. General physical examination revealed a moderately built and nourished individual. He had a deformed nose with depressed nasal bridge. There was diffuse involvement of the face and trunk in the form of multiple coalescing erythematous infiltrated plaques. A well-defined hypoesthetic plaque was seen over the right knee, as illustrated in [Figure 1]. Ulnar, superficial radial, and lateral popliteal nerves were found to be thickened and palpable bilaterally. Lateral madarosis was seen bilaterally [Figure 2]. Bilateral lower limbs revealed pitting edema. On presentation, the patient had a systolic blood pressure of 60 mmHg, pulse was feeble with a rate of 124/min, and SpO2 was 87% at room air. The patient was managed with intravenous normal saline and his vitals stabilized with 3 L of fluids. Empirical antibiotics were started in view of complaints of fever, cough, pain abdomen, and vomiting.
Initial hematological workup showed normocytic normochromic anemia with hemoglobin of 5.6 g/L and leukocytosis with neutrophilia. Two units of packed red blood cells were transfused. Chest radiograph revealed multiple fluffy opacities in the bilateral lung fields likely tubercular in etiology [Figure 3]. Sputum for Gram stain was negative and culture showed growth of normal flora. Acid-fast bacilli were not seen on AFB stain, but sputum for CBNAAT was positive for Mycobacterium tuberculosis. Blood culture was negative for any pathogenic flora. G6PD levels were within normal limits (10.64 U/g Hb). Split skin smear showed a bacterial index of 6+ and morphological index of 90%.
|Figure 3: Chest radiograph showing bilateral fluffy radio-opacities in the upper and middle zones suggestive of pulmonary tuberculosis|
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Skin punch biopsy from the back showed that epidermis was thinned out and there was a focal loss of rete ridges [Figure 4]. A clear grenz zone was seen in between dermis and epidermis. Dermis also showed the presence of ill-defined epithelioid cell granulomas along with large collection of histiocytes forming globi predominantly around periadnexal structures, thus confirming the diagnosis of lepromatous leprosy [Figure 4]. Staining for lepra bacilli was highly positive. However, in these cases, apart from leprosy and cutaneous TB, other differential diagnoses of isolated cutaneous nodules should also be considered. These include syphilis, sarcoidosis, cutaneous neoplasm, neurofibromatosis, cutaneous leishmaniasis, and adult-onset Still's disease. In our case also, these differentials were ruled out after skin punch biopsy. Although nerve thickening is common in leprosy, Pathania et al. presented cases in which even classical involvement of nerves and paresthesia was not present with ulceronodular lesions and still possibility of leprosy was kept, which was confirmed on histopathology, highlighting uncommon presentation in postelimination era.
|Figure 4: Photomicrograph showing slightly thinned epidermis with a grenz zone (black arrow) under epidermis. Dermis is packed with foamy histiocytes (red arrow) which on lepra stain shows globi (inset) of lepra bacilli (H and E, ×200)|
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Contrast-enhanced computed tomography (CECT) of the chest revealed patches of consolidation with centrilobular nodules scattered in bilateral lung fields, more so in the upper lobes [Figure 5]. In addition, ill-defined patch of consolidation were seen in the anteroposterior segment of the left upper lobe with areas of cavitations and hyperdense contents within the areas of breakdown. CECT abdomen revealed multiple granulomas in the spleen and liver. There were prominent proximal and mid-ileal loops with mild thickening at the ileocecal junction. Enlarged lymph nodes were seen in mediastinal (largest 1.1 cm), retroperitoneal, and mesenteric locations (largest 1.7 cm in the left preaortic region) [Figure 6]. The above features in conjunction with positive sputum CBNAAT test lead to a diagnosis of disseminated TB.
|Figure 5: Coronal section of computed tomography chest images a and b showing bilateral upper lobe lung involvement in the form of patchy consolidation (red arrows) with centrilobular nodules|
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|Figure 6: Contrast-enhanced computed tomography abdomen (coronal image) showing dilated mid-ileal loops (green arrow) and abdominal lymphadenopathy (red arrow)|
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The patient was started initially on clofazimine 50 mg once a day along with the empirical antibiotics. The conventional multidrug therapy for multibacillary leprosy which also includes rifampicin and dapsone was not started due to associated suspicion of TB and presence of severe anemia, respectively. With further diagnosis of disseminated TB, standard anti-TB therapy was started and clofazimine continued. No evidence of lepra reactions was seen. The patient showed improvement in appetite and fever and was discharged on the 15th day of hospitalization. As such, it has been observed that diagnosis and management of lepra reactions remained undiagnosed, which can complicate further with variable and atypical presentations, therefore, meticulous therapeutic strategy is to be kept in mind.
Outcome and follow-up
A telephonic follow-up consultation due to ongoing pandemic revealed that he had stopped taking the prescribed drugs and redeveloped fever, resulting in a fatal outcome.
| Discussion|| |
The precise relationship of leprosy and TB and their repercussions on the prevalence of each other remains debateable. The principal mode of transmission in both is via aerosols. The incubation period in leprosy is long and varies from months to years or more, while in case of TB, it is just around 4 weeks. Chaussinand observed in several different settings that the prevalence of leprosy had an inverse association with the prevalence of TB. He subsequently proposed a hypothesis that past exposure to TB leads to cross-immunization of sufferers to leprosy which might have contributed to the mysterious decline of leprosy in Europe. Lietman et al. tested this hypothesis formally by assessing the level of cross-immunity that would be required for M. tuberculosis to competitively exclude Mycobacterium leprae and concluded that if the fundamental reproductive time of leprosy was comparatively low, then, as Chaussinand proposed, TB could have played a major role in the abovementioned significant epidemiological outcome in Western Europe. Leprosy failed to come back in areas where TB had been controlled with extensive BCG vaccination suggesting the provision of immunity against leprosy as well. In a study by Ohara et al., mice immunized with recombinant M. bovis BCG showed reduced multiplication of M. leprae in the footpads, further supporting the evidence of cross-immunity. On the other hand, Donoghue et al. refuted this theory of cross-immunity by demonstrating the presence of widespread M. leprae and M. tuberculosis coinfection using DNA-PCR in human archaeological samples from the Roman period. It is also implicated that decreased cellular immunity in MB leprosy patients coupled with social impact led to either reactivation or superinfection with TB.
Despite the literature supporting both coinfection and cross-immunity theories, only sparse case reports are available for coinfection. A review of data from three leprosy referral centers in Hyderabad, India, over a period of 13 years identified three cases of this coinfection. Rajagopala et al. in 2012 reviewed extensively all previous cases of dual infection reported in the literature and found out 156 such cases. Dual infections were found to have higher morbidity (5.5%) and mortality (37.2%). The time period between the diagnosis of leprosy and TB in a patient is highly variable as per the data analyzed in the past. The study with the biggest data showed a gap duration ranging from 6 months to 15 years. Usually, leprosy predates TB, but the reverse has also been reported as by Agnihotri et al. in 1973. In our case, both the diseases were diagnosed simultaneously.
Revich et al. in 1954 reported the association to be highest in lepromatous leprosy followed by borderline and uncommon in tuberculoid form. In leprosy and TB coinfection, most of the reported cases had pulmonary TB while in few extra-pulmonary TB was also reported. Only one previous case report exists where a 26-year-old male was diagnosed with concurrent disseminated TB. Further reports also show that TB is more severe in a patient coinfected with leprosy. Donoghue et al. also stated that multibacillary leprosy was associated with higher mortality from TB. In our case, it was again lepromatous leprosy but was associated with extensive disseminated TB. The coinfection was obviously more severe, as evidenced by rapid clinical deterioration and patient demise.
The well-known risk factors for TB are HIV infection, silicosis, low socioeconomic profile, diabetes mellitus, gastrectomy, steroids or other immunosuppressant medications, renal failure, and organ transplant recipients. In the year 2000, Chandrashekhar et al. reported the occurrence of pulmonary TB following corticosteroid intake in two cases of leprosy. In the same year, Agarwal et al. reported a case of mycobacterial coinfection in a patient with renal transplant who had taken prednisolone, azathioprine, and cyclosporine for nearly a decade. However, in the TRIPOD studies, no incidence of TB was observed among 300 patients followed over 2 years and who were on prednisone and multidrug therapy for Hansen's. In our case, the patient had none of the above risk factors except for belonging to lower socioeconomic status. In a study conducted in Northwest Louisiana, it was exposure to armadillos as a risk factor for leprosy in patients with nonhealing rashes.
Interferon-gamma release assays (IGRAs) for latent TB can be falsely positive in scenario of coinfection. Despite recent advancement in technology, histopathology and a well-prepared Fite-Faraco stain still remain the cornerstone for diagnosis of leprosy. In our case, both slit skin smear and skin biopsy were diagnostic for leprosy. Treatment of TB in leprosy coinfection remains the same, and the WHO treatment categorization is followed similarly. Rifampicin is a critical component in the treatment schedule for both TB and leprosy. However, if the cases of leprosy with undiagnosed TB are put on monthly rifampicin, this would carry a severe risk of developing drug resistance. So the patients who cannot be started on rifampicin or till such time that patient is being worked up for TB, minocycline should be given as 100 mg daily as a temporary replacement. Once TB is diagnosed, the patient may be started on RHZE with dapsone. To rule out a coinfection, all leprosy cases should ideally undergo a chest radiograph with or without sputum examination as routine initial workup, especially in the presence of respiratory symptoms, constitutional symptoms such as weight and appetite loss, or a high erythrocyte sedimentation rate.
| Conclusion|| |
Both TB and leprosy are a great public health-care concern. Literature gives evidence supporting twin mycobacterial coinfection and cross-immunity theories, but none can explain all the interactions individually. It is imperative to screen out the clinical features of TB in each and every patient of leprosy to avoid single-drug therapy with rifampicin which is a highly bactericidal, first-line antitubercular drug. Monotherapy in missed coinfection may facilitate the emergence of acquired drug resistance and reduced efficacy of anti-TB therapy.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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