Hamdan Medical Joumal 2015; 883-96 (htp/éedo.org/10.7707/h) 320) REVIEW Leprosy in pregnancy - a review of the literature Christiana Oluwashola Fatola,' Anthony Kodzo-Grey Venyo,? Lucy Kodzo-Grey Venyo? and Douglas John Lindsay Maloney* ‘Department of Ear Nose and Throat, North Manchester General Hospital, Manchester, UK, 2Department of Urology, North Manchester General Hospital, Manchester, UK, 2Division of Anaesthesia, Queen Elizabeth Hospital Critical Care Unit, Gateshead, UK, and “Department of District General Hospital, Keighley, UK Abstract Leprosy, or Hansen's disease, i one ofthe wos odes infections diseases I affects the kin and nee and, if et untreated, leads to defoiy. Every 2 minutes someone is dagrsed wit eps, but, because ofthe ack of education and the stigma suroundng the disease, some people ae diagnosed to late and develop life-changing dsb. Tough a simple couse of mediation, leprosy isan ere cable disease. Literate, such a reported cases and review paper, on leprosy in pregnancy was abianed sng vaious intemet seach engines. Leprosy in regnang isa rarely reported event, but rine counties in Ai, ‘sia and Latin Ameria have cositeed it a pubic heath problem ‘An effective cue for leprosy is arable in the form of matéag therapy, taken for some months, but treatment delayed una Inter tage, there i a hgh sk of dbl. Pegmang is haadous fr ‘women with lps. Is most dangerous ung the thi trimester when infection can lead to adverse obstetic and fetal outcmes, such 25 low bithwegt, prematurity, eave demain the newborn and enthea nodosum inthe pregnant mathe. Documentation on leprosy in pregnangy indicates that pregnancy {snot only a tigger for leprosy but abo an ideal in vio model for resech Leprosy in pregnancy an be treated say and efetvely by combined drug therapy. However, ea detection well-planned health education for eprsy paints and the highest standard of cnc superison during pegnangy are ke states in reducing problems asoated withthe disease and are als the est way to prevent dsl. ‘Correspondence: Christiana Okavashola Fatola, Department of Ear Nose and Throat, North Manchester General Hospital ‘Manchester, UK. Email sholly72@yahoo.com (© 201 The Aub) istopathology, Airedale Introduction Leprosy is an infectious disease which is caused by the bacillus Mycobacterium leprae.’ It affects the skin and nerves and can cause paralysis, muscle weakness and loss of sensation.? Duncan’ stated, in a historical view, that ever since leprosy was first reported, patients with leprosy have endured stigmatization, including laws prohibiting marriage to and allowing jorce from those with leprosy and separation of leprous parents from their children. Pregnancy has long been associated with the first presentation of clinical leprosy or worsening of ing disease.* The ensuing literature review on leprosy in pregnancy is divided into two pars: (1) general overview; and (2) discussion of miscellaneous narrations of reported cases of leprosy in pregnancy. Literature re w Definition and terminology Leprosy, also known as Hansen’s disease, is a chronic cutaneous infectious disease caused by an obligate intracellular bacillus, M. leprae. This organism grows best in the cooler areas of the body, including skin, peripheral nerves, testes, anterior chamber of the eye and upper respiratory tract. Leprosy is a global disease that almost exclusively affects individuals in the developing world 83 Jura pista ©2015 Sheth Hamdan Bn ai A Mien Ard fr Med SeesHamdan Medical Journal 2015; 883-96 (htp/éedok.org/10.7707/hm) 320) fa Epidemiology Leprosy is found sporadically in developing countries ‘and most cases of leprosy in the United States of ‘America occur in immigrants. Leprosy is distributed worldwide, as a result of travel and migration, but it is endemic in tropical countries.® In 2012, the number of cases of leprosy was, globally, 180000. In 2011, approximately 220000 ew cases were diagnosed However, it has also been stated that cases of leprosy significantly decreased from the 1960s to the 2010s” With approximately 250000 new cases detected ‘annually, this disease Isa challenge to health ‘worldwide. It has yet to be eliminated despite implementation of effective multidrug therapy (MDT)? Women who develop leprosy continue to be disadvantaged, with rates of late diagnosis and disability remaining high. Despite the aforementioned aspects of the disease, leprosy was not specified in the United Nations Millennium Development Goals. Nevertheless, there have been improvements in the other areas, such as education and poverty, which will help leprosy patients and services. A retrospective and longitudinal study of 149 cases of pregnant women with leprosy in Paré, Brazil, within a 3-year petiod between 2007 and 2009, showed that the age group with the highest Incidence of the pregnancy-leprosy association was 20- to 39-year-olds? Genetics ‘Anumber of genes have been associated with susceptibility to leprosy. de Messias-Reason et al” reported that about 95% of people are naturally immune to leprosy, but a defect in cell-mediated immunity causes susceptibility to leprosy. The region of DNA responsible for this variability is also linked. to Parkinson's disease, which led Buschman and Skamene” to suggest that the two disorders may be linked, in some way, at the biochemical level Risk factors From previous reviews, there appears to be little interaction between the human immunodeficiency virus and the risk of developing leprosy," however, people living in areas with polluted water and ‘consuming a poor diet, as well as those who suffer from diseases that compromise immunity, are at the highest risk of developing leprosy.” 84 Transmission There is uncertainty regarding the mode of transmission; nevertheless, some authors are of the opinion that M. leprae is spread from person to person via nasal droplets.” Some suggest that leprosy can be transmitted to humans by armadillo. Leprosy is not known to be either sexually transmitted or highly infectious after treatment; regardless, a large number of people are naturally immune and sufferers are no longer infectious after about 2 weeks of treatment’? Causative organism and pathophysiology ‘Mycobacterium leprae is a slow-growing, obligate, intracellular acid-fast bacillus with a predilection for the skin and nerves. This organism has not yet been successfully cultured in vitro" Types of leprosy There are three systems for classifying leprosy. The first system recognizes two types of leprosy based on a person's immune response to the disease, which includes tuberculoid leprosy and lepromatoid leprosy. In leprosy, there is a spectrum of lesions of which the less severe end of the spectrum is tuberculoid leprosy, and the most severe is lepromatous leprosy." Some of the characteristic features of tuberculoid leprosy include the presence of non-necratizing granulomas in the dermis and peripheral nerves and the absence of acid-fast bacilli within the granuloma. The lepromin skin test tends to be positive for tuberculoid leprosy and there also tends to be a predominance of helper CD4+ over CD8+ T lymphocytes at the infection site. Furthermore, tuberculoid tissues are usually rich in the messenger RNAs (mRNAs) of the Th1 family of cytokines* Good immune response and few lesions are associated with tuberculoid leprosy’ Some of the characteristic features of lepromatous leprosy include the presence of sheets of foamy macrophages in the dermis (and at other sites), which tend to contain numerous acid-fast bacilli, and the absence of granulomas. The lepromin skin test is usually negative and there tends to be predominance of suppressor CD8+ over CD4+ T lymphocytes at the infection site. In addition, lepromatous tissues tend to be rich in the mRNAs of Th2 cytokines. Loss of ability to kill bacteria appears to be specific to M. leprae, Patients who have lepromatous leprosy (© 201 The Aub) ual Campion © 2015 Se Hamdan Be as A ton Ard real SensHamdan Medical Joural 2015; 883-96 (htp/éedo.org/10.7707/he 320) i are not usually susceptible to opportunistic infections, cancer or acquired immune deficiency syndrome, and they maintain delayed-type hypersensitivity to Candida, Trichophyton, mumps, tetanus toxoid and tuberculin’ Lepromatous leprosy tends to be associated with a poor immune response and the disease affects the skin, nerves and other organs. Moreover, lepromatous leprosy tends to be more contagious than the other types of leprosy. The second classification system is based on that by the World Health Organization (WHO), which categorizes leprosy based on type and number of skin areas affected by the disease: = Paucibacillary (PB) type - five or fewer lesions with no bacteria detected in the skin smear. = Multibacillary (MB) type ~ more than five lesions or bacteria detected in the skin smear. The third classification system is the Ridley-Jopling, which is used globally in clinical studies. In this system the six classes of leprosy, based on the severity of symptoms, are: f= Intermediate leprosy ~ comprising flat lesions, which tend to heal on their own but can progress to a more severe type of leprosy. 8 Tuberculoid/P8 leprosy - comprising a few flat lesions, some of which can be large and numb (nerves may be affected) but can heal by themselves. It is possible that some tuberculoid lesions may develop into more severe forms. = Borderline tuberculoid (87) leprosy - comprising small and more numerous tuberculoid-like lesions, which may persist and revert to tuberculoid leprosy or advance to another type of leprosy. BT is associated with less nerve enlargement. = Mid-borderline leprosy ~ manifests as reddish plaques and is associated with moderate numbness and swelling of the lymph glands. Lesions may regress, persist or progress to other types of leprosy. = Borderline lepromatous (BL) leprosy ~ comprising many flat lesions, elevated lumps, plaques and nodules that are numb at times. They may persist, regress or progress to another type of leprosy. = Lepromatous/MB leprosy - comprising numerous lesions containing bacteria that do not regress." Associated with hai loss, nerve damage, weakness of the limb and disfigurement. (© 201 The Aub) Leprosy reactions are classified into two categories: type 1 and type 2. However, it is much more urgent to recognize and treat the nerve damage than to classify the type of reaction, Table 1 shows the differences between the two types of reaction. Clinical description Tuberculoid leprosy lesions tend to manifest as macules with a hypopigmented centre and raised erythematous border Lepromatous leprosy manifests as macules, papules and plaques, but firm nodules may also be seen on the face? Borderline leprosy also manifests as hypopigmented macules! Microscopic description The microscopic features of the types of leprosy (Figures 1 to 8) have been summarized as follows: = Microscopic examinations of biopsy specimens of tuberculoid leprosy tend to reveal epithelioid histiocytes encompassing small cutaneous nerves. Cells without evidence of necrosis may also be seen. The infiltrate may affect the papillary dermis Up to the epidermis and this may destroy the arrectores pilorum muscle. In addition, there is usually a scarcity of bacilli in the lesions = With regard to lepromatous leprosy specimens, histological examination tends to reveal macrophages that are located in poorly circumscribed masses in the dermis, with TABLE 1 Leprosy reactions Sign Co Inflammation of The leprosy patches New, tendered the sin are inflamed, but the lumps, not asscated rest ofthe sn is with te leprosy oral pathes General condition God, with tle or no Poor with fever and ofthe patent fever ‘general mabise Timing of Usual ery on in Usually ater in the presentation and the couse of MOT; treatment; only ‘ype of patent people wth oth PB. people with MB and MB Eye invement Wales of eed Intel eye dase closure may ocr its) spose Frome wth permis fa Sunde ow tragic an mony 07 mao. suing ie Twa. Loo: The let Feeatin of aig ‘sons (E202? Capit © 200 HE, London. 85 Jura pista ©2015 Sheth Hamdan Bn ai A Mien Ard fr Med SeesHamdan Medical Journal 2015; 883-96 (htp/éedok.org/10.7707/hm) 320) FIGURE 1 Lepromatous leprosy ~ skin low magnification). Throughout the dermis there isa diffuse dense population ‘of macrophages with no significant lymphocytic ‘component. Reproduced with permission from Hamodat M, ‘Skin-nontumor/clnical dermatology ~ infectious disorders ~ leprosy. Pathology Outlines; 2011, URL: pathologyoutlines ‘com/topic/skinnontumorleprosy html? FIGURE 3 Lepcomatous leprosy ~ skin (acid fast stain) Macrophages distended by numerous leprosy bacill-forming dlobi. Reproduced with permission from Hamodat M. ‘Skin-nontumor/clnical dermatology - infectious disorders ~ leprosy. Pathology Outlines; 2011. URL; pathologyoutlines. ‘com/topic/skinnontumorleprosy.htm> FIGURE 2 Lepromatous leprosy ~ skin. High-power ‘magnification of upper papillary dermis showing foamy macrophages. Reproduced with permission from Hamodat M, Skin-nontumor/clinical dermatology ~ Infectious disorders ~ leprosy. Pathology Outlines; 2011. URL: pathologyoutlines.com/topic/ skinnontumorleprosy.html? 86, FIGURE 4 Lepromatous leprosy ~ skin (acid-fast stain). Large number of bacili within macrophages. Reproduced ‘with permission from Hamodat M, Skin-nontumer/clinical dermatology ~ infectious disorders ~ leprosy. Pathology ‘Outlines; 2011. URL: pathologyoutlines com/topic/ skinnontumorleprosy html? (© 201 The Aub) ual Campion © 2015 Se Hamdan Be as A ton Ard real SensHamdan Medical Joural 2015; 883-96 (htp/éedo.org/10.7707/he 320) FIGURE 5 Lepromatous leprosy ~ spleen (low magnification). Numerous aggregates of foamy macrophages (not {granulomas} lying in splenic parenchyma. Reproduced with permission from Hamodat M. Skin-nontumor/linical dermatology - infectious alsorders ~ leprosy. Pathology Outlines; 2011. URL: pathologyoutines.com/topic/ skinnontumorleprosy.html? FIGURE 7 Tuberculoid leprosy ~ skin (low magnification, rnon-necrotizing granulomas). Numerous non-necrotizing ‘epithelioid granulomas are present and in association with Langhans’ giant cells. Reproduced with permission from Hamodat ML Skin-nontumov/elinical dermatology ~ infectious disorders ~ leprosy. Pathology Outlines; 2011. URL: pathologyoutlines.com/topic/skinnontumorleprosyhtml> FIGURE 6 Lepromatous leprosy ~ spleen. The aggregates: ‘of foamy macrophages are not associated with Langhans’ giant cells and are not forming granulomas. Reproduced with permission from Hamodat M. Skin-nontumor/cinical dermatology ~ infectious disorders ~ leprosy. Pathology Outlines; 2011. URL: pathologyoutlines.comy/topic/ skinnontumorleprosy html? (© 201 The Aub) FIGURE 8 Tuberculoid leprosy - skin (non-necrotizing ‘granuloma). High-power magnification showing a rnon-necrotizing epithelioid granuloma with a peripheral rim of lymphocytes and a Langhans’ giant cal Reproduced with permission from Hamodat M. ‘Skin-nontumor/cinical dermatology ~ infectious dlsorders ~ leprosy. Pathology Outlines; 2011. URL: pathologyoutlines. ‘com/topie/skinnontumorleprosy html? Jura pista ©2015 Sheth Hamdan Bn ai A Mien Ard fr Med SeesHamdan Medical Journal 2015; 883-96 (htp/éedok.org/10.7707/hm) 320) fa absent or scant numbers of lymphocytes. The macrophages may be distended with globi (large groups of leprosy bacilli). A large number of bacteria is usually seen in cutaneous nerves, the endothelium and the media of small and large vessels; these may invade the arrectores pilorum muscle. Lepromatous leprosy may also be associated with subcutaneous nodules, which may develop into erythema nodosum of leprosy = With regard to BL leprosy specimens, examination tends to reveal an onion skin pattern. For this form of leprosy there is more circumscription of the granulomatous response, more lymphocytes and a closer association with nerves? = With regard to indeterminate leprosy, histological ‘examination tends to reveal scanty superficial and deep lymphohistiocytic infiltrate in the dermi with a tendency to localize around appendages, and increased numbers of mast cells” = With regard to histiocytoid leprosy, histological examination tends to reveal spindle cell proliferation with a storiform pattern, which is indicative of fibrous histiocytoma Modified ZiehI-Neelsen stain (Wade-Fite staining), a type of skin test, is positive in leprosy. Diagnosis Diagnosis of leprosy can be established using polymerase chain reaction (PCR), as most skin lesions have no identifiable bacteria.” Matsuda reactions, which occur following intradermal injection of armadillo-derived lepra bacilli, are useful for classification of leprosy.” Fibrous histiocytoma is a differential diagnosis of leprosy.* Clinical features ‘As the mycobacterium causing leprosy is slow growing, symptoms can take years to appear after ‘exposure. The incubation period is usually 3 to 5 years.° The complexity with which leprosy presents is related to the varied immunological responses? The clinical signs of leprosy are related to the immunological status of the host. Hormonal changes during puberty and pregnancy can also ‘cause variation in the host's immune status? Tuberculoid leprosy occurs in individuals who have ‘good cell-mediated immunity. These patients develop a granulomatous response. Lepromatous leprosy occurs in individuals who have poor cell-mediated immunity. These patients do not develop a granulomatous responses Borderline leprosy is a form of leprosy that is intermediate between tuberculoid and lepromatous leprosy’ Leprosy is transmitted by nasal discharge and digital impregnation of the skin, as bacilli can be carried under nails and then inoculated under the skin by scratching Plantar leprosy lesions are thought to be a high risk for the development of squamous cell carcinoma."® In pregnancy, painful erythematous lesions of the skin on the face and limbs have been reported. Women who are afflicted with Hansen’s disease, including those who have been cured during pregnancy or the post-partum period, have a high risk of degenerating nerve function.” During late pregnancy and lactation, these women may also experience reactivation, relapse and transient exacerbation.” Leprosy reactions are triggered by pregnancy. ‘Type 1 reaction [reversal reaction (RR)] occurs during puerperium when cellular immunity returns to normal. Type 2 reaction [erythema nodosum leprosum (ENL}] peaks in the third trimester of pregnancy and during breast feeding, and neurological damage occurs earlier in these cases than in patients who are not pregnant” Both types of reaction continue long into lactation.*2" Complications of leprosy in pregnancy Duncan et a2" suggested that the adverse effects of pregnancy on leprosy are associated with suppression of maternal cell-mediated immunity during gestation and recovery post partum. ‘The risks to the mother and fetus are directly proportional to the bacterial load of the disease and there is an increased risk of premature birth and. delivery of small-for-gestational age infants? Neuritis affects almost half of pregnant women who also have leprosy and, in most cases, silent neuritis, which causes loss of both sensory and motor function and is associated with reaction and relapse? The risk of leprosy symptoms being more severe is, high during pregnancy, which may lead to permanent (© 201 The Aub) ual Campion © 2015 Se Hamdan Be as A ton Ard real SensHamdan Medical Joural 2015; 883-96 (htp/éedo.org/10.7707/he 320) i nerve damage, the most commonly affected being the ulnar, median and peroneal nerves.? Children born to mothers with leprosy have low birthweights, small placentae and grow slowly.” Screening in pregnancy Askin smear is a useful test to confirm very Infectious cases when itis difficult to be sure of the diagnosis on clinical grounds alone; however, many leprosy patients will have a negative skin smear. This means that, although they have leprosy bacilli in their body, there are too few to be seen in the smear and this will affect the type of treatment needed.” The Mitsuda test, which is also known as a lepromin test, measures the immune response against intradermally injected lepromin. It has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy.”* Skin biopsy, nasal smears or both are used to assess the presence of acid-fast bacili using a Fite stain Biopsies should be full-dermal thickness, taken from ‘an edge of the lesion that appears most active.” Serological assays can be used to detect phenolic stated that leprosy is usually well controlled by MDT. Nevertheless, in case of non-compliance or leprosy reactions, management, may be challenging. They reported a 33-year-old Brazilian woman with lepromatous leprosy who had been treated with MDT for 1 year and whose treatment had been discontinued in view of the fact that she wanted to have children. Two months after discontinuation of her medications, she developed a severe and recalcitrant ENL. Histological examination of a biopsy specimen revealed thrombosed small veins and neutrophilic inflammation in fat septa without arteritis. During her pregnancy and ensuing lactation period, glucocorticoids were the only suitable drug. Eickelmann et al” stated that with the use of the shortened WHO/MDT regimen (1 year vs. 2 years of treatment), ENL would probably be seen more often after leprosy therapy was complete. Furthermore, it would need to be rapidly recognized and treated to avoid damage to some organs such as eyes or kidneys. Duncan et al stated that a few prospective studies to ascertain the development of leprosy in the pre-sulfone and early sulfone years of children of leprous parents had been undertaken but no studies were made of the growth and development of these children. Duncan et al conducted a study between 1975 and 2003 with follow-up of both mothers and their babies. The study included 156 pregnant women who had various types of leprosy: 36 non-leprous, 25 tuberculoid and BT leprosy (celeased from treatment), 18 tuberculoid and 8T leprosy (active), 42 BL leprosy and 35 lepromatous leprosy. They found that babies of mothers with leprosy had complications such as lower birthweights, smaller placentae, slower growth, more infections and higher infant mortality than those of non-leprous mothers. The findings were most marked. in babies of mothers with lepromatous leprosy. (© 201 The Aub) ual Campion © 2015 Se Hamdan Be as A ton Ard real SensHamdan Medical Joural 2015; 883-96 (htp/éedo.org/10.7707/he 320) fa Growth in childhood was uneventful infants of mothers with lepromatous leprosy tended to catch up by 3.6 years of age. Children with lepromatous mothers had more infections in childhood than those from nor-leprous mothers. The puberty skeletal growth spurt, and menarche for the girls, was delayed in children from mothers with leprosy, in ‘comparison with a new healthy control group, but these children would catch up by their late teens. The aforementioned findings were most marked in children from mothers with lepromatous leprosy. Duncan et al concluded that impaired growth in utero and infancy is probably the result of immunological factors, but they could find no ‘explanation for the delayed growth in adolescent children of mothers with lepromatous leprosy. In 2007, Bbddinghaus et al* reported a case of leprosy in a 29-year-old pregnant Asian woman who presented with joint pain and multiple disseminated erythematous macules, papules and plaques. Biopsies of her skin lesions, which were then subjected to histological examination and staining for acid-fast bacilli, confirmed the clinical suspicion of a cutaneous mycobacterial disease. They iterated that both histological examination and staining for acid-fast bacilli should be performed for all patients with unidentified skin lesions. They further stated that, in thelr case, the definitive laboratory diagnosis of leprosy was achieved using a species-specific real-time PCR on samples from infected tissues. Lockwood and Sinha” examined the interaction between pregnancy, leprosy and leprosy reactions in a systematic literature review. They identified several retrospective case series and one retrospective cohort study but only one prospective cohort study. They reported that: = In the post-partum period, itis highly likely that. type 1 RRs will occur. This temporal association was also observed for both overt and silent neuritis. = Type 2 (ENL) reactions were also observed throughout pregnancy and during lactation. This, type of reaction may be severe and recurrent. They did not find any prospective, controlled studies that documented the complications of pregnancy in women treated with MDT regimens. ‘= They highlighted the need for prospective, controlled studies, with appropriate controls, on women throughout pregnancy and lactation so that risk factors for reaction and neuritis during pregnancy could be identified and quantified (© 201 The Aub) Duncan* stated that women who are afflicted with leprosy or cured of the disease run a serious risk of deterioration in nerve function when they become pregnant. During pregnancy and lactation, relapse and reactivation of leprosy may occur, as well as transient exacerbation maximally in late pregnancy. ENL in the first and third trimesters may lead to nerve damage post partum. Type 1 RR maximally occurs in the post-partum period, even after MOT and after release from treatment (RFT). Neurtis affects about half of women with leprosy during pregnancy/lactation, as well as after MDT-RFT, as ‘silent’ neuritis with new motor and sensory loss in the majority of cases, and stocking-and-glove anaesthesia in women with PB and post MOT-RFT. Patients incubating the infection tend to develop overt disease. The cycle of this disease can only be terminated by a combination of: (1) eprologists and, leprosy control personnel who understand the problems of leprosy in pregnant and lactating ‘mothers; (2) well-planned health education for leprosy patients, and both leprosy and maternal health-care workers; and (3) the highest standard of clinical supervision during pregnancy, prolonged lactation and at regular intervals during the woman's reproductive life, even after she would normally be released from surveillance after completion of MDT. Lyde undertook a cohort study over a 6-year period in 40 patients with leprosy, in which three pregnancies were reported. In the first patient, symptoms of the disease appeared during pregnancy. In the second patient, a type 1 reaction occurred during pregnancy; the patient had been treated previously. In the third patient, the fetus was exposed to three antimicrobial drugs during the first trimester. Lyde® made the ensuing concluding statements: fw Pregnancy causes a relative decrease in cellular immunity, which allows the organism causing leprosy to proliferate, which may worsen the disease state leading to permanent nerve damage. = Careful management of reactional states and treatment of patients with dapsone monotherapy could prevent this nerve damage. 1a Infants tend to be less affected than their mothers; nevertheless, selection of the mother's antimicrobial regimen should ensure adequate control of the bacteria while avoiding teratogenicity and in utero adverse effects. a” ou amp © 201 Sheth Hamdan Ba A koa a Me! SnesHamdan Medical Journal 2015; 883-96 (htp/éedok.org/10.7707/hm) 320) fa Lopes and Sarno™ reported on 20 cases of pregnant ‘women who had been afflicted by leprosy: eight with lepromatous leprosy, seven with BL leprosy, four with tuberculoid leprosy and only one with indeterminate leprosy. Three of the patients presented with symptoms during pregnancy, ‘while in another they manifested post partum. Pathological examination was positive in 13 patients but negative in seven patients. The Mitsuda test ‘was negative in 16 patients, positive in two patients ‘and not performed for the other two patients. Fourteen patients had polychemotherapy, which ‘comprises diaminodiphenyisulfone, rifampicin and clofazimine. Three of the patients had dapsone monotherapy. Three of the patients started treatment after delivery. Patients who developed reactive states were treated with corticosteroids and aspirin. Nine of the cases received continuous treatment, while eight had irregular treatment. Ten patients developed reactions: eight of them developed during pregnancy, one in puerperium. and one in the lactation period. Eight had ENL and ‘two had an RR. One newborn presented with ‘exfoliative dermatitis in the first hours after birth; his mother had used sulfone during pregnancy. With regard to the 20 babies, five weighed less than 2.5kg and four were premature. They concluded that the reaction states of patients and low birthweight of premature babies occurred, in lepromatous and BL cases.” Rodriguez-Pazos et a stated that, even though pregnancy has considerable influence on the course of the leprosy, there had been very few studies on the subject. They reported a 34-year-old Brazilian ‘woman, living in Spain for 3 years, who presented ith a 2-week history of painful, erythematous lesions on the face and limbs. She described swelling and pain in her left foot. She had been in good health but had reported a hypopigmented lesion on her right arm which had been present since she was a child, she did not have any symptoms associated with the lesion which had grown progressively. She had not considered the lesion to be of any importance until it became ‘erythematous and painful, coinciding with the appearance of the other lesions. She had previously worked with leprosy patients for 4 years. At the time of reporting, she had three children, the youngest of whom was 2 months old. On ‘examination, she was found to have numerous, well-delimited, infiltrated erythematous plaques 92 cn her limbs and face. Their surface was hairless. Some of the lesions had a raised border with a flat and hypopigmented centre. The pinna of her right ear was infiltrated and erythematous. She underwent a number of tests, including a full laboratory work-up, and radiographs of the chest and left foot were obtained, as well as ultrasound scans of the abdomen, which were normal She also had a Mantoux test, which was negative. Furthermore, she was subjected to neurological examinations which revealed a clear-cut diminution in sensation of temperature, pain and touch in the affected areas. A biopsy and histological examination of one of the plaques revealed a sarcoid-type granulomatous infiltrate which had involved the {ull thickness of the dermis, following the path of the neurovascular bundles towards the surface. Peripheral nerves were not observed. ZiehI-Neelsen staining of the specimen did not show any acid- and alcoholfast bacilli. The Ziehl-Neelsen stain was also negative on a sample of lymphatic fluid from the pinna of the ear and scrapings from the nasal septum. The aforementioned clinical pi was consideted to be compatible with a type 1 lepra reaction, triggered after delivery, in the course of a tuberculoid form of leprosy which had remained undetected for several years. She was treated with rifampicin 600mg/month, dapsone 100mg/day and prednisone 40mg/day in a tapering regimen. The swelling and pain in the left foot disappeared after a few days. The skin lesions showed a slower but nevertheless favourable response. Rodriguez-Pazos et al.® iterated the salient points about leprosy that have been made by other authors as follows: 1m Pregnancy may be associated with the development of both type 1 and type 2 lepra reactions. Type 1 reactions quite often develop during the puerperium, when cellular immunity returns to normal levels. Type 2 reactions may ‘occur during pregnancy or the lactation period, and neurological damage tends to occur earlier in these than in patients who are not pregnant2>* = Furthermore, the risk for the development of the disease and of disease recurrence in previously treated patients is higher during pregnancy." = A follow-up study of healthy pregnant women in an endemic area, by Duncan et al, found that 69% had developed leprosy, whereas the frequency was only 0.1% in the general population in the same area. (© 201 The Aub) ual Campion © 2015 Se Hamdan Be as A ton Ard real SensHamdan Medical Joural 2015; 883-96 (htp/éedo.org/10.7707/he 320) i a The main complication with regards to these patients is neuritis. In a follow-up study of pregnant women who had leprosy, 44% of them were found to have developed neuritis, of whom 27% were clinically silent* a Silent neuritis does produce a decrease in distal sensitivity, which is not associated with pain, swelling or paralysis. Silent neuritis is particularly common in the third trimester and post-partum period. It has been recommended that periodic neurological examination should be undertaken during the third trimester and post-partum period, regardless of the symptoms with which a patient presents, in order to allow for early detection and in order to avoid possible progression towards irreversible nerve damage. There is a high risk of prematurity and low birthweight for the newborn. It is important to follow up these children after delivery, in view of the fact that, sporadic cases of the appearance of leprosy lesions have been reported in the first months of life.” tu The risks for the mother and fetus are directly proportional to the bacterial load of the disease. In view of this, WHO has recommended the same treatment in both pregnant and non-pregnant women. In the PB forms of the disease, the treatment is based on the use of sulfone and rifampicin, while in the MB forms of the disease treatment is based on sulfone, rifampicin and clofazimine. Rifampicin is regarded as essential, as it is the most bactericidal. Although no controlled studies in women have been reported, MDT would not appear to be associated with a higher risk of abortions or congenital malformations. Children born to mothers who had been treated with clofazimine may develop a transitory hyperpigmentation at birth. it has been recommended that vitamin K should be given to the infants of mothers who had been treated with rifampicin in order to avoid post-natal haemorrhages. Haemolytic anaemia, which may be induced by sulfone, may add to the physiological anaemia of pregnancy. Lepra reactions may be treated with oral corticosteroids and clofazimine. Thalidomide (Thalidomide Celgene®, Celgene Ltd, Summit, NJ, USA), and thicamides, which are sometimes used as alternatives to clofazimine, are contraindicated during pregnancy." (© 201 The Aub) Rodriguez-Pazos et al concluded by stating that in view of the growing number of patients with leprosy who have been migrating from endemic areas, clinicians would need to be aware of the effects of pregnancy on leprosy and its specific management during this period, Summary Leprosy is a chronic disease caused by M. leprae. ‘The disease mainly affects the skin and nerves and, if untreated, it can cause permanent damage. Leprosy reactions are triggered by pregnancy. Type 1 reaction (RR) occurs during the puerperium when cellular immunity returns to normal, while type 2 reaction (ENL) peaks in the third trimester of pregnancy and during breast feeding, and neurological damage ‘occurs earlier in these patients than in those who are not pregnant. Both types of reaction continue long into lactation. Neuritis affects almost 50% of pregnant women, in most cases as silent neuritis with loss of both sensory and motor function associated with reaction and relapse, Leprosy is usually well controlled by MDT. Nevertheless, in the case of non-compliance or leprosy reactions, it may present a therapeutic challenge. It is believed that suppression of maternal cell mediated immunity during pregnancy and recovery post partum is responsible for the adverse effects of Hansen's disease in pregnancy. Conclusions Pregnancy induces a state of immunological change which may lead to worsening of leprosy in the mother, as well as precipitation of leprosy reactions, which may result in irreversible nerve damage to the mother; this may also affect the infant. However, leprosy in pregnancy can be safely and successfully treated with MDT. All pregnant and lactating women should be treated at referral level under supervision and monitored after completion of MDT. Leprosy in pregnancy has implications for: (1) the physician, (2) the obstetrician/gynaecologist, 93 ou amp © 201 Sheth Hamdan Ba A koa a Me! SnesHamdan Medical Journal 2015; 883-96 (htp/éedok.org/10.7707/hm) 320) fa (3) the leprosy health worker, and (4) the paediatrician, 12 as well as (5) the family and friends of the pregnant ‘woman, all of whom provide support and care to the patient. Conflict of interest We have no conflict of interest to declare. Acknowledgements We acknowledge Dr Nat Pernick, President of Pathology Outlines.com, who, on behalf of PathologyOutlines.com, granted us permission to reproduce figures from the website of PathologyOutlines.com. References a 4 15 16 ” 1 Groenen G, Saunderson PR. How to diagnose and treat 18 leprosy. Learning Guide One. London: The International Federation of Ant-Leprosy Associations (LEP); 2001 2. Saunderson P. How to recognise and manage leprosy 19 reactions. Learning Guide Two. 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