Leprosy is an infectious disease which is caused by the bacillus Mycobacterium leprae.1 It affects the skin and nerves and can cause paralysis, muscle weakness and loss of sensation.2 Duncan3 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 divorce 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 existing disease.4 The ensuing literature review on leprosy in pregnancy is divided into two parts: (1) general overview; and (2) discussion of miscellaneous narrations of reported cases of leprosy in pregnancy.
Definition and terminology
Leprosy, also known as Hansen’s disease,5 is a chronic cutaneous infectious disease caused by an obligate intracellular bacillus, M. leprae.1,5 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.
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.5
In 2012, the number of cases of leprosy was, globally, 180 000.6 In 2011, approximately 220 000 new cases were diagnosed.6 However, it has also been stated that cases of leprosy significantly decreased from the 1960s to the 2010s.7
With approximately 250 000 new cases detected annually, this disease is a challenge to health worldwide. It has yet to be eliminated despite implementation of effective multidrug therapy (MDT).7
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 Pará, Brazil, within a 3-year period between 2007 and 2009, showed that the age group with the highest incidence of the pregnancy–leprosy association was 20- to 39-year-olds.8
A number of genes have been associated with susceptibility to leprosy. de Messias-Reason et al.9 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 Skamene10 to suggest that the two disorders may be linked, in some way, at the biochemical level.
From previous reviews, there appears to be little interaction between the human immunodeficiency virus and the risk of developing leprosy;11 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.12
There is uncertainty regarding the mode of transmission;12 nevertheless, some authors are of the opinion that M. leprae is spread from person to person via nasal droplets.7 Some suggest that leprosy can be transmitted to humans by armadillos.13,14 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.9
Causative organism and pathophysiology
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.5
Some of the characteristic features of tuberculoid leprosy include the presence of non-necrotizing 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.5 Good immune response and few lesions are associated with tuberculoid leprosy.5
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 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.5 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:
Intermediate leprosy – comprising flat lesions, which tend to heal on their own but can progress to a more severe type of leprosy.
Tuberculoid/PB 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 (BT) 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.16 Associated with hair loss, nerve damage, weakness of the limb and disfigurement.
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.
Reproduced with permission from Saunderson P. How to recognise and manage leprosy reactions. Learning Guide Two. London: The International Federation of Anti-Leprosy Associations (ILEP); 2002.2 Copyright © 2002 ILEP, London.
Tuberculoid leprosy lesions tend to manifest as macules with a hypopigmented centre and raised erythematous border.5 Lepromatous leprosy manifests as macules, papules and plaques, but firm nodules may also be seen on the face.5 Borderline leprosy also manifests as hypopigmented macules.5
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.5
With regard to lepromatous leprosy specimens, histological examination tends to reveal macrophages that are located in poorly circumscribed masses in the dermis, with 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.5
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.5
With regard to indeterminate leprosy, histological examination tends to reveal scanty superficial and deep lymphohistiocytic infiltrate in the dermis, with a tendency to localize around appendages, and increased numbers of mast cells.5
With regard to histiocytoid leprosy, histological examination tends to reveal spindle cell proliferation with a storiform pattern, which is indicative of fibrous histiocytoma.5
Modified Ziehl–Neelsen stain (Wade–Fite staining), a type of skin test, is positive in leprosy.5
Diagnosis of leprosy can be established using polymerase chain reaction (PCR), as most skin lesions have no identifiable bacteria.17 Matsuda reactions, which occur following intradermal injection of armadillo-derived lepra bacilli, are useful for classification of leprosy.5
Fibrous histiocytoma is a differential diagnosis of leprosy.5
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.5 The complexity with which leprosy presents is related to the varied immunological responses.5 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.3
Tuberculoid leprosy occurs in individuals who have good cell-mediated immunity. These patients develop a granulomatous response.5
Lepromatous leprosy occurs in individuals who have poor cell-mediated immunity. These patients do not develop a granulomatous response.5
Borderline leprosy is a form of leprosy that is intermediate between tuberculoid and lepromatous leprosy.5
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.5
Plantar leprosy lesions are thought to be a high risk for the development of squamous cell carcinoma.18
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.19 During late pregnancy and lactation, these women may also experience reactivation, relapse and transient exacerbation.19
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.20 Both types of reaction continue long into lactation.3,20
Complications of leprosy in pregnancy
Duncan et al.21 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.22,23 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.3,19,20,24 The risk of leprosy symptoms being more severe is high during pregnancy, which may lead to permanent nerve damage,25 the most commonly affected being the ulnar, median and peroneal nerves.2
Children born to mothers with leprosy have low birthweights, small placentae and grow slowly.17
Screening in pregnancy
A skin smear is a useful test to confirm very infectious cases when it is 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.1
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.26
Skin biopsy, nasal smears or both are used to assess the presence of acid-fast bacilli using a Fite stain. Biopsies should be full-dermal thickness, taken from an edge of the lesion that appears most active.27
Serological assays can be used to detect phenolic glycolipid-1 (specific for M. leprae).27
Serological tests for the detection of M. leprae antibodies or antigens are the fluorescent antibody absorption test and phenolic glycolipid-1 (PGL-1) enzyme-linked immunosorbent assay (ELISA), which has been further simplified as dot ELISA and dipstick ELISA. Patients seropositive for PGL-1 have an increased risk of relapse, and the level of PGL-1 may be used as an indicator of bacterial load in these patients.28
A follow-up is essential for children born to mothers with leprosy, as leprosy lesions have been known to appear in the first few months following birth.21
Leprosy medications used in pregnancy
Leprosy is usually well controlled with a combination of drugs known as MDT. This is also recommended by WHO. These drugs include dapsone, rifampicin and clofazimine. The treatment varies according to whether the leprosy has been classified as PB or MB (Tables 2 and 3).1
|Monthly dose under supervision||Rifampicin 600 mg|
|Daily dose||Dapsone 100 mg|
Modified from Gimovsky AC, Macri CJ. Leprosy in pregnant woman, United States. Emerg Infect Dis 2013; 19:1693–4.29
|Monthly dose||Rifampicin 600 mg|
|Clofazimine 300 mg|
|Daily dose||Dapsone 100 mg|
|Clofazimine 50 mg|
Modified from Gimovsky AC, Macri CJ. Leprosy in pregnant woman, United States. Emerg Infect Dis 2013; 19:1693–4.29
Rifampicin is essential, as it is the most bactericidal, but it can cause post-natal haemorrhage in infants from mothers that received treatment; therefore, vitamin K should be administered to these infants to avoid this condition.21
Clofazimine, effective when administered daily in high doses, causes chronic abdominal pain and discoloration of the skin, particularly in people with light skin.2 Oral corticosteroids and clofazimine can be used to treat lepra reactions in pregnancy. Low-dose prednisolone (30mg, reducing the dose gradually) to treat leprosy reactions during pregnancy is also advised to avoid growth retardation and adrenal suppression in the newborn.1
As a result of immunodeficiency in pregnancy, lepromatous leprosy and relapse after treatment are commonly seen throughout pregnancy.29
Miscellaneous narrations from reported cases and studies
Gimovsky and Macri29 reported that leprosy in pregnancy is rare in the USA. WHO documented a total of 213 036 new cases of leprosy, throughout the world, in 2009, and stated that nine countries in Africa, Asia and Latin America considered it to be a public health problem, accounting for about three-quarters of the global disease prevalence.30
Gimovsky and Macri29 reported a case of leprosy in a pregnant 27-year-old Mexican woman, who already had one child. At her initial prenatal visit, about week 24 of gestation, the patient reported that she had observed subcutaneous nodules on various parts of her body, including her arms, legs, back and abdomen, about 5 months prior to the prenatal visit and 2 weeks prior to her last menstruation. Biopsy and histological examination of a skin lesion revealed acute and chronic panniculitis with acid-fast bacilli. Diagnosis was confirmed, using PCR, to be lepromatous leprosy. This woman was treated with rifampicin, dapsone, clofazimine and prednisolone (Lodotra®, Napp Pharmaceuticals Ltd, Cambridge, UK). The patient was closely monitored with serial ultrasound scans, which revealed consistent fetal growth at the 50th percentile. At about 37 weeks of gestation, her membranes had ruptured and she underwent a caesarean delivery, taking into consideration that the method of leprosy transmission is not yet proven and to prevent possible vertical mother-to-child transmission. The patient delivered a female infant, weighing 2.95 kg with good Apgar scores of 8 in 1 minute and 9 in 10 minutes. On the first post-operative day, the patient was restarted on dapsone treatment; she received dapsone, 50 mg daily, and prednisone, 40 mg daily. The patient was discharged with her infant on the third post-operative day.
Lockwood and Sinha31 postulated that pregnancy causes a relative decrease in cellular immunity, which enables the organism M. leprae to proliferate.
It has been suggested that permanent nerve damage can be prevented by careful management and that lepromatous leprosy and relapse after treatment are more commonly encountered throughout pregnancy because of the pregnant woman’s immune-deficient state.31,32
It has also been stated that infants tend to be less affected than mothers; nevertheless, selection of the mother’s antimicrobial drug regimen option must ensure adequate control of the bacteria while avoiding teratogenicity and in utero adverse effects, such as low birthweight.22,32 Furthermore, the infant, potentially, has a high risk of contracting leprosy from the mother by skin-to-skin contact or droplet transmission, particularly if the mother has not received treatment.
Palácios et al.8 stated that few previous publications had reported pregnancy to be associated with exacerbation of leprosy. They conducted a study8 that aimed to describe the rate of detection of this association in Pará, Brazil, by county and integration region from 2007 to 2009 via an analysis of sociodemographic, epidemiological and operational indices. During the study period, 149 associations were detected, with 14 hyperendemic counties: seven in 2007, five in 2008 and two in 2009. They concluded that their analyses had revealed that the surveillance programme was still unsatisfactory in Pará. The interpretation of the endemicity parameters had enabled qualitative and quantitative analyses to determine the epidemiological panorama of this association. The identification of high endemicity required further clarification.
Eickelmann et al.33 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.33 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.34 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.34 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 (released from treatment), 18 tuberculoid and BT 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. 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 non-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.34 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, Böddinghaus et al.15 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 their case, the definitive laboratory diagnosis of leprosy was achieved using a species-specific real-time PCR on samples from infected tissues.
Lockwood and Sinha31 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, it is 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.
Duncan20 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 MDT and after release from treatment (RFT). Neuritis 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 MDT–RFT. Patients incubating the infection tend to develop overt disease. The cycle of this disease can only be terminated by a combination of: (1) leprologists 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.
Lyde35 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.
Lyde35 made the ensuing concluding statements:
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.
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.
Lopes and Sarno36 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 diaminodiphenylsulfone, 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 2.5 kg and four were premature.
They concluded that the reaction states of patients and low birthweight of premature babies occurred in lepromatous and BL cases.37
Rodríguez-Pazos et al.25 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 with 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 on 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 full thickness of the dermis, following the path of the neurovascular bundles towards the surface. Peripheral nerves were not observed. Ziehl–Neelsen staining of the specimen did not show any acid- and alcohol-fast 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 picture was considered 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 600 mg/month, dapsone 100 mg/day and prednisone 40 mg/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.
Rodríguez-Pazos et al.25 iterated the salient points about leprosy that have been made by other authors as follows:
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 pregnant.38
A follow-up study of healthy pregnant women in an endemic area, by Duncan et al.,32 found that 6% had developed leprosy, whereas the frequency was only 0.1% in the general population in the same area.
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.24
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.39
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 thioamides, which are sometimes used as alternatives to clofazimine, are contraindicated during pregnancy.32,40
Rodríguez-Pazos et al.25 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.
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.
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, (3) the leprosy health worker, and (4) the paediatrician, as well as (5) the family and friends of the pregnant woman, all of whom provide support and care to the patient.