Health Burden of Hansen's Disease in Central India: A 4-Year Retrospective Study.

BACKGROUND: Despite the implementation of multidrug therapy by WHO to treat Hansen's disease (HD), new case detection rates are still high indicating active transmission. AIMS AND
OBJECTIVES: To study the clinical profile of HD in central India along with its epidemiological characteristics.
MATERIALS AND METHODS: Medical records of clinically diagnosed Hansen's patients were recruited retrospectively during January 2015 to December 2018. Case records were evaluated with respect to demographic, clinical, histopathological, and bacteriological investigations, development of reaction, and deformities. Patients were classified based on Ridley Jopling classification and treated accordingly. Statistical analysis was done using proportion, mean, and percentage.
RESULTS: A total of 400 new patients were enrolled and males outnumbered females. Maximum cases, 115 (28.75%), were in the age group of 31-40 years. Sixteen (4%) cases belonged to the pediatric age (less than 18 years) group. Most common clinical spectrum was borderline lepromatous (n = 156, 39%) followed by lepromatous HD (n = 120, 30%). Eleven patients had pure neuritic HD and nine had histoid HD. Grade 2 deformity was found in 52 and grade 1 deformity was found in 16 patients. Most common lepra reaction was type 2 lepra reaction (n = 112, 28%). Thirteen (3.25%) patients were of relapse of HD among which maximum eight were BL HD followed by LL HD three (0.75%) and TT HD two (0.5%).
CONCLUSION: Early diagnosis is very important for timely and proper implementation of treatment which will prevent sequelae and physical disabilities that can have an impact on the individual's social and working life, which are responsible for stigma and prejudice regarding the disease. Detection of this huge number of cases signifies a high burden of HD in this area even in the post elimination era. Copyright:

Introduction

Hansen's disease (HD), more commonly known as Leprosy, is a chronic granulomatous disease caused by Mycobacterium leprae (M. leprae) which primarily affects the nerves and skin and secondarily other organs.[1] Leprosy still continues to be one of the major public health problems in many countries including India. There were 2,16,108 new leprosy cases registered globally in 2016, according to official figures from 145 countries from the 6 World Health Organization (WHO) Regions. The global prevalence rate was 0.29/10,000 at the end of 2016.[2] In India, a total of 1,35,485 new cases were detected during the year 2016-17, which gave Annual New Case Detection Rate (ANCDR) of 10.17 per 1,00,000 population.[3] Although India achieved the elimination target of HD of less than 1 case per 10,000 population in December 2005, even today HD continues to be a cause of significant public health concern.[4] The prevalence rates of HD in the pediatric age group in various studies vary from 5.1% to 11.43% in India.[5] HD in pediatric age group indicates a hidden reservoir of infective cases in the community, the usual source of contact being the family members, neighbours, or contact from fellow students in the schools where they are studying.[1]

Worst affected regions in India include Bihar, Orissa, Chhattisgarh, Gujarat, Jharkhand, MP, Maharashtra, Dadra and Nagar Haveli, Lakshadweep, etc. where prevalence is found to be more than 2 in many districts.[3] Accurate diagnosis of HD is of elementary importance to all aspects of the disease including social aspects, epidemiology, case management, and the prevention of disabilities. Delay in the diagnosis and misdiagnosis of HD are more common due to long incubation period and atypical clinical presentation.[6] Government has recently launched the Leprosy Case Detection Campaign (LCDC) for early detection of HD and for providing timely treatment. Hence, the current study was undertaken to study the clinical features of HD and estimate pediatric cases of HD.

Materials and Methods

This was a retrospective cross-sectional study in which medical records of all Hansen's patients from prefilled proformas, attending the department of Dermato-Venereo-Leprology, during January 2015 to December 2018 were analysed. Medical records of the patients including age, sex, occupation, address, marital status, onset of lesions, duration of lesions, associated symptoms, history of previous treatment, and family history were analyzed.

Detailed cutaneous examination including morphology, peripheral nerve palpation, sensory, motor and cranial nerve examination, and investigations including slit skin smear and histopathological examination were analyzed from predesigned proformas. Based on history, clinical examination, and investigations, a diagnosis of HD was made and patients were classified based on Ridley Jopling classification as tuberculoid (TT) HD, borderline tuberculoid (BT) HD, midborderline (BB) HD, borderline lepromatous (BL) HD, and lepromatous (LL) HD. In addition to these, patients who did not have any cutaneous findings with significant nerve conduction abnormalities were classified under pure neuritic (PN) HD. All diagnosed patients were treated with Paucibacillary (PB) therapy (MDT)/Multibacillary MB-MDT based on their spectrum and patients were followed up for any lepra reaction, side effects of multidrug therapy, and deformity. Statistical analysis was done using mean, proportion, and percentage.

Results and Observations

Total 400 new patients with HD were enrolled among which 250 were males and 150 were females (M:F ratio = 1.67) [Graph 1]. Age of the patients ranged from 14 to 76 years. Maximum cases (n = 115, 28.75%) were in the age group of 31–40 years. Forty-five cases belonged to the age group above 60 years, while sixteen belonged to age less than 18 years [Table 1]. Primary cutaneous manifestation was observed in 389 (97.25%). Most common clinical spectrum was BL HD (n = 156, 39%) followed by LL HD (n = 120, 11.5%). Eleven (2.75%) patients had PN HD, while nine (2.25%) had histoid HD [Table 2 and Figures 1, 2]. BT HD was the most common spectrum reported in the pediatric age group (n = 6). Positive contact history was present in 12 (75%) children.

Graph 1

Sex wise distribution

Table 1

Agewise distribution

Age (years)	0-10	11-20	21-30	31-40	41-50	51-60	61-70
2015	0	0	9	11	2	0	2
2016	2	5	12	11	13	2	2
2017	2	7	26	33	16	13	9
2018	0	11	50	60	42	28	32
Total	4	23	97	115	73	43	45

Table 2

Clinical spectrum of HD

Spectrum	Percentage	Number
TT	7.5%	30
BT	16.75%	67
BB	1.75%	7
BL	39%	156
LL	11.5%	120
Histoid	2.25%	9
Pure neuritic	2.75%	11

Figure 1

(a) Patch of tuberculoid Hansen's disease over forearm. (b) Patches of borderline tuberculoid Hansen's disease over back. (c) Patches of midbordeline Hansen's disease over trunk. (d) Lesions of borderline lepromatous Hansen's disease over face

Figure 2

(a) Patches of borderline Hansen's disease over trunk, (b) leonine facies, (c) histoid lesions over abdomen, and (d) histoid lesions over forearm

Overall, the most common site in TT HD was head and neck region 12 (40%) and of BT HD was upper limb 37 (55.22%). The most common site of lesion in the pediatric age group was upper limb (43.75%) [Table 3]. Most common morphological type present in LL HD was nodular 56 (46.67%) followed by plaque 37 (9.25%) and diffuse 37 (9.25%).

Table 3

Distribution of lesions in children (spectrum TT HD and BT HD)

Site of lesion	Year
	2015	2016	2017	2018
	Upper limbs	4	2	-	5
	Lower limbs	2	-	-	6
Trunk	1	-	-	4
Head and neck	1	-	1	10

Most common lepra reaction reported was type 2 lepra reaction (n = 103, 25.75%) followed by type 1 lepra reaction (n = 20, 5%). Type 2 lepra reaction occurred commonly in BL spectrum (n = 53, 13.25%), whereas type 1 reaction occurred most commonly in BT spectrum (n = 15, 3.75%) [Graph 2 and Figure 3].

Graph 2

Lepra reaction

Figure 3

(a and b) Type 1 Lepra reaction with involvement of face, back, and buttocks; (c) Erythema nodosum leprosum over face and trunk

Most common deformity reported was grade 2 (n = 52, 13%) followed by grade 1 deformity (n = 16, 4%) both occurring commonly in BL HD [Graph 3]. Most common type of deformity was trophic ulcer (n = 28, 7%), followed by ulnar claw hand (n = 17, 4.25%) [Table 4 and Figure 4].

Graph 3

Deformity distribution

Table 4

Yearwise distribution of deformities in HD

Year	Deformity
	Claw hand	Foot drop	Trophic ulcer	Saddle nose
	2015	1	0	0	0
	2016	2	0	4	0
2017	2	0	5	0
2018	12	3	19	4
Total	17	3	28	4

Figure 4

Deformity: (a) saddle nose, (b) trophic ulcer, (c) ulnar claw hand

In patients with cutaneous manifestations, skin biopsy was done and histopathological examination performed and it was noted that 171 (42.75%) of cases showed clinicopathological correlation (CPC). Maximum CPC 24 (80%) was observed in the TT group of patients [Table 5].

Table 5

Clinicopathological correlation

Year	TT	TT (HP)	BT	BT (HP)	BB	BB (HP)	BL	BL (HP)	LL	LL (HP)	HH	HH (HP)	PN	PN (HP)
2015	5	3	5	1	0	0	8	1	3	0	2	0	1	0
2016	3	2	11	7	1	1	23	10	8	0	0	0	1	0
2017	3	2	15	9	0	0	38	16	44	14	3	1	3	0
2018	19	17	36	15	6	2	87	34	65	32	4	4	6	0
Total	30	24	67	32	7	3	156	61	120	46	9	5	11	0

Three hundred seventy-seven (94.25%) patients were treated with MB-MDT while twenty-three (5.75%) were treated with PB-MDT according to WHO guideline. Thirteen (3.25%) patients were of relapse of HD among which maximum eight were BL HD followed by LL HD three (0.75%) and TT HD two (0.5%). Relapse patients were diagnosed as per the criteria shown in Table 6.[78]

Table 6

Criteria for relapse

The first three criteria are sufficient to make a diagnosis of relapse; criteria 4 and 5 are additional and may be used wherever facilities are available.
1.	Clinical criteria	Increase in size and extent of existing lesion(s) appearance of new lesion(s) infiltration and erythema in lesions that had completely subsided nerve involvement (thickening or tenderness)
2.	Bacteriological criteria	Positivity (in a smear-negative patient) at any site in skin smears for AFB at two examinations during the period of surveillance is diagnostic of relapse. In patients with a positive BI, if BI increases by 2+ over previous smears at any two sites and continues to be so at two examinations, it is diagnosed as relapse, provided the patient has ingested 75% of the drugs.
3.	Therapeutic criteria	This is useful when reversal reaction is suspected. The patient may be treated with prednisolone (reaction dose being around 1 mg/kg/day), after which a reversal reaction should subside completely in 2 months. If symptoms do not subside or only partially subside or lesions persist or increase under the cover of steroid, relapse should be suspected.
4.	Histopathological criteria	This includes the reappearance of granuloma in PB cases and increased macrophage infiltration with solid-staining bacilli and increasing BI in MB cases.
5.	Serologic criteria	In LL cases, the measurement of PGL-1 IgM antibodies is a good indicator of relapse.

Discussion

HD produces a spectrum of clinical phenotypes. The type 1 reaction, which most commonly occurs in the BT, BB, and BL forms, is characterized by erythema and swelling in the preexisting lesions, fever, and neuritis.[9] The most common clinical presentation of type 2 reaction, i.e., erythema nodosum leprosum, is most commonly found in BL and LL HD and is characterized by the sudden manifestation of erythematous tender nodules which are frequently accompanied by fever, malaise, neuritis.[9]

This study included 400 patients which showed slightly higher preponderance in males (M:F- 1.67:1) which was similar to studies done by Thakkar and Patel, Adil et al., and Patil and Sherkhane.[4910] This indicates that males are more vulnerable to HD because of their greater mobility and increased opportunities for contact in big population. Majority of patients belonged to age group 31–40 years (n = 107, 26.75%) which is in concordance with Adil et al. (n = 60, 26.7%).[4] Childhood leprosy accounts for 4% (16) which is lower as compared to 14.2% (32) in Adil et al. and 12.3% (31) in Thakkar and Patel.[49] These differences may be due to the difference in the cut of age of these studies. Maximum cases of HD were from Nagpur, Amravati, Chandrapur, Seoni, Chindwara, and Balaghat (central India) as compared to other studies which were from different regions of India [Table 7].

Table 7

Comparison with other studies

	Our study	Adil et al. (2008) [Uttar Pradesh]	Thakkar and Patel (2014) [Vadodara]	Patil and Sherkhane (2016) [Karnataka]
Number of patients	400	225	250	114
M:F ratio	1.67:1	2.08:1	1.7:1	3.97:1
Most common spectrum	BL HD (39%)	BL HD (38.2%)	TT HD (29.2%)	-
Histoid HD	2.25%	1.78%	-	-
Pure neuritic HD	2.75%	1.33%	18%	-
Childhood leprosy Positive contact	75%	-	48.3%	-
Lepra reactions (most common)	32.25%	12.9%	9.6%	-
	Type 2 in BL HD	Type 2	Type 2	-
Deformities (most common)	17% Grade 2 (mc Trophic ulcer in BL HD)	-	42.8%	82.46%
		-	Grade 1	Grade 2
Clinicopathological correlation	42.75%	-	60%	-
Relapse	3.25%(13)	-	-	-

The present study revealed that maximum cases in the clinical spectrum of HD were BL HD (n = 156, 39%) which is similar to Adil et al. (n = 86, 38.2%).[4] Second most common spectrum found in our study was LL HD (30%) followed by TT HD (7.5%). In this study, 2.75% (11) patients were of pure neuritic HD which is in consistence with Adil et al. (n = 3, 1.33%) and very less as compared to Thakkar and Patel (n = 45, 18%) and Kolleri et al. (n = 75, 8.5%).[4911] 2.25% (11) patients of histoid HD were diagnosed in our study which is parallel to Adil et al. (1.78%).[4] The incidence of histoid HD reported in India varies from 2.79% to 3.60%.[12] In children, BT HD (n = 6, 42.85% of total children) was most commonly reported in our study which is in concordance with Ghunawat et al. (n = 90, 71.64%).[5] Positive contact history in children was 75%. Positive contact history in childhood leprosy was seen in 48.3% and 18% by Thakkar and Patel and Mohammed et al., respectively.[913] Close contacts with leprosy case are an important cause of transmission in children which may be due to lower immune status as compared to elders. An overall most common site in TT HD was head and neck region 12 (40%) and BT HD was upper limb 37 (55.22%). The most common site of lesion in the pediatric age group was extremities (87.5%) similar to the study by Nair.[1] Most common morphological type in LL HD in our study was nodular.

Deformities in this study were 17% (68) of patients which comprised commonly of grade 2 (n = 52, 13%) followed by grade 1 (n = 16, 4%). This was very less as compared to Patil and Sherkhane where 82.46% (94) of patients showed deformities, comprised 11.41% (13) patients of grade 1 and 71.05% (81) of grade 2.[10] As per Thakkar and Patel, 42.8% patients showed deformity which comprised 73% (29.2) patients of grade 1 and 34%(13.6) of grade 2.[9] Most common type of deformity in our study recorded was trophic ulcer (n = 28, 7%) in BL HD.

Lepra reactions were seen in 32.25% (129), whereas Thakkar and Patel and Adil et al. showed 9.6% (24) and 12.9% patients of lepra reactions, respectively. In lepra reactions, type 2 reaction (n = 112, 28%) is much more common than type 1 (n = 17, 4.25%) reaction in our study. Similar observations have been made by Thakkar and Patel who observed type 2 lepra reactions (n = 16,6.4%) common than type 1 reaction (n = 8,3.2%).[49] We also recorded that most common spectrum showing type 2 lepra reactions was BL HD.

HD cases show diversities between the clinical and histopathological features. In the present study, the histopathological characteristics were consistent with the clinical diagnosis in 42.75% patients. In a study conducted by Arunagirinathan et al., the histopathological features were consistent with clinical diagnosis in 62.85%.[14] Thakkar and Patel showed 60% patients' histopathological characteristics consistent with the clinical diagnosis.[9] Thirteen (3.25%) patients were of relapse of HD which was most commonly recorded in BL HD.

This study gives a broad view of the scenario of HD in central India but as it was conducted in a tertiary care hospital, it is not illustrative of the circumstances on the field. The large percentage of multibacillary cases signifies that leprosy awareness and programs need to be more vigorously implemented along with facilities for investigations and rampant provision of treatment. An innovative approach to target vulnerable groups needs to be devised to achieve complete eradication of this peril from the community.

Conclusion

To the best of our knowledge, this is first study of HD in central India which addresses clinicoepidemiological and histopathological characteristics and associated deformities. Detection of this huge number of cases signifies a high burden of HD in this area even in the post elimination era. In our study, males outnumbered females with borderline lepromatous as most common spectrum of HD. 2.25% of histoid HD cases in post elimination era is an eye opener for vigilant detailed history, clinical examination, and investigations. The occurrence of childhood HD disease in children is alarming and signifies active disease transmission. 3.25% of relapse cases of HD were diagnosed, which was not seen in other studies, and is a cause of concern suggesting the importance of proper counseling and treatment. Therefore, in an endemic country like India, we still need to have an open eye to recognize the varied manifestations of leprosy and treat accordingly.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.