European Journal of Cardiovascular Medicine

Leprosy is a well-known disease (Hansen’s Disease) since the days of Sushruta and Charkas and is caused by Mycobacterium leprae. In Vedic reference, it is mentioned as “Kusht Rog” [1]. It is one of the important causes of permanent physical deformity and the social stigma attached to it grossly increases the level of stress in the affected individual [2].

Leprosy is a neglected tropical disease that is considered rare in most regions despite having relatively high incidence in some countries. It is caused by infections with Mycobacterium leprae and Mycobacterium lepromatosis. Mode of transmission for this infection occurs via droplets during close and frequent contact with untreated cases.Both M. leprae and M. lepromatosis are slow-growing bacteria with incubation periods varying from 5 to 10 years, depending on clinical subtypes.The clinical presentations of leprosy include skin rash, peripheral neuropathy, and organ deformities [3,4].

1. lep­rae usually affects the skin and the peripheral nerves but has a wide range of clinical manifestations and spread from person to person, primarily as a droplet nasal infection, is widely prevalent in India. After the introduction of Multidrug therapy (MDT), the country achieved elimination status.

In the absence of an effective vaccine, early diagnosis and treatment of the disease are important to stop the transmission of M. leprae, reduce the risk of physical disability and deformity, and reduce the physical, psychosocial, and economic burden of the disease [5,6]. Due to difficulties in diagnosis, lack of scientific studies on leprosy, and largely unknown outcomes in patients with leprosy, childhood leprosy reflects early exposure to M. leprae but remains neglected [7-9].

Despite advances in all spheres ofmedical science, leprosy continues to bea public health challenge in countries likeIndia.[10] The objective of this case series is to discuss unusual patterns of leprosy encountered at our superspeciality hospital and to increase the awareness among clinicians regarding such diagnostic dilemmas.

STUDY

Thisprospective single centre observational study was conducted for duration of 3 months between August to September 2024at the mycobacteriology laboratory in apex healthcare centre of North India. All clinically suspected cases of lepromatous leprosy who came for slit skin smear sampling were included in the study.  Slit skin smear biopsy was performed in these patients. Samples were collected from the following sites 1) Ear lobes 2) above eye brows 3) from lesions. Smears were stained by Z-N (ZiehlNeelsen) stain with 5% H₂SO₄ and seen at 100X magnification for acid fast bacilli.

 Case-1   A 20-year-old male was admitted to the hospitalfor the evaluation of loss of sensation and ulcers on both hands and legs. He had loss of sensation in left hand one and half years back. He developed pustules on left hand and both foot, after few days these pustules converted into ulcers in both foot. There was disfigurement of three fingers in left hand. There was no history of madarosis /hair fall for which he visited to neurology department where diagnosis of Mononeuritis multiplex was made but after treatment symptoms didnot subsided. To rule out leprosy patient was sent to mycobacteriology laboratory for slit skin smear which came out to be positive.Further section from nerve biopsy shows nerve bundles with perineural mild fibrosis along with focal perineural and intraneural lymphocytic infiltrate along with occasional foamy histiocytessuggestive of Indeterminate leprosy. He was started with oral dapsone 100 mg daily, clofazimine 50 mg daily, and rifampin 600 mg daily. On follow up patient got relief from symptoms.

Case-2-A 21-year-oldfemale with no significant medicalhistorypresented withfever and swelling all over the bodyin the past 5 months, she also developed papules on face, back and on legs. Gradually there was loss of sensation on right foot due to which she was unable to walk properly. She also gave history of madarosis on right side. Therewas history of hypopigmented patches on back. Forall these conditions she visited hospital and slit skin smear biopsy was performed which came positive. Antileprosy medications initiatedand on follow upher skin lesions promptly flattened and got relief from symptoms.

Case-3-A 59-year-old male came to dermatology OPD with loss of sensation on both legs and in left hand since one and half year. Papules were present on left hand which further developed in ulcers and deformities. There washistory of white hypopigmentedpatches. He visited many hospitals but diagnosis was not made and his condition was not improving. When he visited dermatology OPD, he was advised for slit skin smear which was positive for M.leprae. He was started on oral dapsone 100 mgdaily, clofazimine 50 mg daily, and rifampin 600 mg daily and continued drug therapy. Patient got relieved from his symptoms.

Case-4-A 52 years female developed fever two months back along with that there was severe pain in her hands and legs due to which she was unable to walk properly. Both hand and foot of right side was involved.Therewas no history of ulcers, loss of sensation or hypopigmented patches. We took slit skin smear which was positive for M.leprae bacilli after which treatment was provided and on follow up patient reported resolution of pain and gait improvement.

Case-5-A17-year-old male patient, having history of loss of sensation on right side of hand for more than 6 years for which he visited many doctorsbut the diagnosis wasn’t made.He then visited tertiary caremedicine department theirneurological examination revealed decreasedtemperature sensation and proprioception in a stocking‑glovedistribution over the right hands. There was claw hand deformity on right side, associated with numbness of medial aspect of right upper limb, below elbow and medial two and half fingers. No history of ulcers, madarosis or hairloss. The patient was referred to dermatology for further skin biopsy and from there patient was sent to mycobacteriology laboratory for slit skin smear examination which reported the smear positive for M. leprae.Treatment started one and half months back and patient has got relief from the symptoms. Fortunately in this long standing case no sequelae and deformity reported.

CASE 6-A 45 years old female patient visitedto dermatology for treatment of hypopigmented patches on her face for more than 10years without any deformity but loss of proprioception, after clinical examination she was sent for slit skin smear which came positive for leprae bacilli. After treatment she responded well and hypopigmented patches also subsided

Figure 1: Various manifestations of M.leprae infections 1A. Maculopapular rashes ; 1B Madarosis;Figure 1C Claw hand

Table1: Patient Demographics, skin lesions, histopathology findings.

The present study included a detailed description of six cases that were diagnosed at a tertiary care hospital in Lucknow, India. We diagnosed six cases of leprosy in 2024, some with unusual manifestations presenting significant diagnostic challenges.

Among 15 patients who attended our tertiary care hopsital in North India for leprosy examination,6 were positive for leprae bacilli.

A systematic review included 30 studies occurring between 2010 to 2020, spanning 10 countries and comprising 11,353 leprosy patients. The 10 countries included India (10), Philippines (1), Brazil (7), Ethiopia (2), China (3), Madagascar (1), Iran (1), Saudi Arabia (1), Nigeria (2) and Bangladesh (2). The leprosy patient sample sizes of the included studies ranged from 39 to 4,775, among which, the data of male, female, multibacillary (MB), paucibacillary (PB), grade 2 deformity (G2D), age < 15 years, and age ≥ 15 years were collected. In the quality assessment, quality scores of the included studies ranged from 5 to 9, and contained 16 medium quality and 14 high quality studies. Altogether, the 27 studies contained a sample size of 11,091 leprosy patients, among which, the reported male proportion ranged from 39.3% to 83.9%. The pooled proportion of males to females was 63% (95% CI 59%-66%) to 37% (95% CI 34%-41%), respectively. The result of the degree of heterogeneity inconsistency (I²) was 91.3% (P < 0.001) [11].

The tribal population of India accounts for just 8.6 per cent of the overall population. However, 18.5 per cent of the new leprosy cases were detected within the tribal community in the year 2020, indicating a disproportionately high burden of leprosy among the tribal population. Recent data suggest that these health disparities can be mainly related to the increased marginalization of tribal population as compared to other communities. This shows the need to further explore the current situation of leprosy in tribal populations so that suitable interventions can address the contributing factors, leading to health inequalities in disadvantaged socio-economic groups [12].

Among positive patients five of them visited in out-patient department while one was admitted in department of medicine.Contact history was present in only 1 patient. Most of the patients were from rural areas.  Out of 6, only 2 patients presented with nonhealing ulcer, and three initially sought help from primary care providers. Only two patients developed subjective numbness. Leprosy was not suspected before skin biopsy in three cases, while non-infectious diagnoses were considered, including mycosis fungoides, erythema multiforme, vasculitis, and amyloidosis. In the other two cases, leprosy was in the initial differential diagnosis. Ultimately, the diagnosis of leprosy was established in all six individuals based on clinical presentation, slit skin smear. Routine histopathology was able to detect the bacilli only in one case. This case series highlights the importance of leprosy, especially in the Northern India where its incidence is increasing despite the prominent elimination program going on in country.

There was another study by NipornJariyakulwong et al., in 2022 stated that the the most reasonable cause of her diagnosis is a history of close contact with her father-in-law who was diagnosed with leprosy 30 years ago. This incubation period was particularly long and has not been usually reported in human leprosy cases. However, this long incubation period for leprosy has been reported in chimpanzees.⁸ This reminds healthcare providers that proper surveillance of leprosy should not be neglected. Patients may undergo a subclinical stage for decades and present symptoms in unusual regions after their international migration.⁷ Moreover, since leprosy is one of the greatest imitators of other skin diseases, a complete history taking could be helpful for an appropriate differential diagnosis [13].

We observed a sudden rise in number of leprosy cases detected at our lab. Though the sample size is not significant, however 5+ cases out of 15 are significant to draw attention to this.

Leprosy remains a public health problem in many developing countries, especially, in tropical regions. Since the causative Mycobacterium spp. are slow-growing, people may have subclinical leprosy for years. The international migration and importation of workers from one country to another could be a cause of expansion of leprosy from endemic areas to uncommon areas. The long incubation period of this disease makes it difficult to estimate its real incidence and eradication.

While leprosy treatment is free in India as also around the world, the cost of travel and the associated loss of wages, failure of surveillance mechanisms in endemic areas and a lack of information about the availability of treatment are significant barriers to treatment. Discontinuation of specialized leprosy hospitals and stopping the treatment follow up and surveillance activities can contribute to poor adherence to treatment [14,15].

Inadequate compliance to treatment is a major issue with tribal populations as they undertake short-term migration making them prone to leave their treatment incomplete, thereby increasing the chances of emergence of drug resistance. Regular monitoring of the cases released from treatment and relapse cases is also needed to further reduce leprosy burden [16].

The result of this study points to the fact that there is still circulation oflepra bacilli in the community in the “elimination era.” It also highlights the need for early diagnosis and appropriate treatment at the field level to prevent the spread of bacilli anddevelopment of disabilities.

DECLARATIONS:

Conflicts of interest: There is no any conflict of interest associated with this study

Consent to participate: There is consent to participate.

Consent for publication: There is consent for the publication of this paper.

Authors' contributions: Author equally contributed the work

1. Leprosy in India. Bhattacharya S, Sehgal V (1999).
2. Govindasamy K, Jacob I, Solomon RM, Darlong J. Burden of de­pression and anxiety among leprosy affected and associated factors-A cross-sectional study from India. PLoSNegl Trop Dis. 2021; 15: e0009030.
3. World Health Organization. Towards zero leprosy. Global leprosy (Hansen's Disease) Strategy 2021–2030Word Health Organization Regional Office for South-East Asia, New Delhi (2021), p. 30
4. E. Tan, Y.W. Yeo, D.J.Q. Ang, M.M.F. Chan, S.M. Pang, L.H. Sng. Report of a Leprosy case in Singapore: an age-old disease not to be forgotten in developed countries with low-prevalence settings. Access Microbiol, 1 (2019), Article e000014
5. Ghosh S., Chaudhuri S. Chronicles of Gerhard Henrik Armauer Hansen’s life and work. Indian Journal of Dermatology . 2015; 60(3):p. 219.
6. Prakoeswa C., Reza N., Alinda M., Listiawan M., Thio H. B., Kusumaputro B. Pediatric leprosy profile in the postelimination era: a study from Surabaya, Indonesia. American Journal of Tropical Medicine and Hygiene . 2022; 106.
7. Mohanty P., Naaz F., Bansal A. K., Kumar D., Gupta U. D. Challenges beyond elimination in leprosy. International Journal of Mycobacteriology . 2017; 6(3):p. 222.
8. Moraes P. C., Eidt L. M., Koehler A., Pagani D. M., Scroferneker M. L. Epidemiological characteristics and trends of leprosy in children and adolescents under 15 years old in a low-endemic State in Southern Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo . 2021; 63:p. e80.
9. Rumbaut Castillo R., Hurtado Gascón L. C., Ruiz-Fuentes J. L., et al. Leprosy in children in Cuba: epidemiological and clinical description of 50 cases from 2012–2019. PLoS Neglected Tropical Diseases . 2021;15(10).
10. Rao PN, Suneetha S. Current Situation of Leprosy in India and its Future Implications. Indian Dermatol Online J. 2018 Mar-Apr;9(2):83-89. doi: 10.4103/idoj.IDOJ_282_17. PMID: 29644191; PMCID: PMC5885632.
11. Jing Yang et al. Global epidemiology of leprosy from 2010 to 2020: A systematic review and meta-analysis of the proportion of sex, type, grade 2 deformity and age. Pathog Glob Health. 2022 May 4;116(8):467–476.
12. Mukul Sharma , Pushpendra Singh et al. Epidemiological scenario of leprosy in marginalized communities of India: Focus on scheduled tribes. Indian J Med Res . 2023 Jan 5;156(2):218–227.
13. NipornJariyakulwong et al. Lepromatous leprosy with a suspected 30-year incubation period: A case report of a practically eradicated area. Journal of Taibah University Medical Sciences. 2022; 17 (4): 602-605.
14. Avanzi C, Singh P, Truman RW, Suffys PN. Molecular epidemiology of leprosy:An update. Infect Genet Evol. 2020;86:104581.
15. Deps P, Collin SM. Mycobacterium lepromatosis as a second agent of Hansen's disease. Front Microbiol. 2021; 12:698588.
16. 16. Rathod SP, Jagati A, Chowdhary P. Disabilities in leprosy:An open, retrospective analyses of institutional records. An Bras Dermatol. 2020;95:52–6.