Last updated: July 20, 2019
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Hansens disease or Hansen’s disease has been around for 1000s of old ages, with mentions to the disease being found as far back as 1550 B.C. Treatment of Hansen’s disease was non understood for many old ages and so patients were excluded from conventional society for a long clip due to the physical symptoms that are associated with status. It was n’t until the 1940 ‘s when modern antibiotics became available that Hansen’s disease could be treated instead than merely being managed that so called “ leper settlements ” began to fall out of favour.1

Leprosy has been the focal point riddance programme backed by the World Health Organisation pledge since 1991 for the “ riddance of Hansen’s disease as a public wellness job by the twelvemonth 2000 ” 2 which has been defined in existent footings as the decrease in the figure of patients that will have antibiotic intervention to less than 1 in 10000. 107 out of the 122 state ‘s that were defined as being epidemic in 1985 have seen decreases in interventions rates down to ‘elimination ‘ criterions.


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Leprosy is caused by the acid fast bacilli Mycobacterium leprae, with its primary modesty being Humans. M. Leprae can non be cultured in vitro nevertheless it can be cultured in nine-banded armadillo and in mouse padders supplying all the samples that are required for surveies. This has allowed the analysis of the bacteria and now the full genome has been published. Analysis on the genome shows M. Leprae is related to the M. TB bacteria, nevertheless over half the functional cistrons of M. TB are lost in the M. Leprae bacteria, including some that are required for some metabolic tracts. This may explicate why the bacteria is unable to last in vitro and long doubling clip of 14 yearss as it may necessitate the hosts own metabolic tract to derive the necessary foods it requires. The cell wall of M. Leprae is thought to be mostly responsible to the opposition to the organic structure ‘s immune responses. The cell wall is similar to the remainder of the Mycobaterium species and is portion of the genome that was non lost. Mycolic acids make up about 60 % of the cell wall and are attributed to the acid-fast stating. The external cell wall contains many open proteins that are alone to each species, and it is this complex mixture of polyoses and glycolipids that makes the bacteria impenetrable to many solutes without specific conveyance systems.


The path of transmittal of M. Leprae has non been wholly proven nevertheless the primary path is thought to be by aerosol spread and consumption with though the repertory system, much like Tuberculosis. Most people are really immune to M. leprae, nevertheless there are certain genotypes that are susceptible to infection including both Human and non-Human leucocyte antigens.

Like transmittal the existent pathogenesis of Leprosy is non really good understood, but grounds suggests that the clinical manifestations within the patient are chiefly due to the immune response and can be classified by either the Ridley-Jopling Scale or the World Health Organisation ( WHO ) . Normally the WHO ranking is combined with the Ridley-Jopling graduated table to make up one’s mind which drug intervention should be recommended. Since we are covering with multibacillary Hansen’s disease we know that the response is chiefly down to the Th2-type cellular immune responses which normally leads to multiple progressive tegument lesions and may affect peripheral nervousnesss.

Clinical Manifestation

Since the pathogenesis of Leprosy has a big graduated table of fluctuation patients can show with heterogenous clinical manifestations of the disease. It is non merely the presentation of symptoms that can change besides the clip from infection to clinical manifestation which can run from a few months to 30-40 old ages. Some of the common symptoms of Hansen’s disease are skin lesions, failing or numbness caused by nervus harm and burn or ulcers in anesthetic custodies or pess.

Skin Damage – Normally the tegument lesions are maculas or plaques ; nevertheless seldom papules and nodules can be seen. Since we are covering with Multibacilliary Hansen’s disease there are big Numberss of lesions and can change in size, form and location, lesions can be hypopigmented or erythematous. If patients are more mid-borderline signifier of leprosy so these lesions can be immulogically unstable.

Nerve Damage – Nerve harm can happen in two parts, peripherally at the nervus short pantss and in the little cuticular nervousnesss. Peripherally the bacteria attacks the nervousnesss near the surface of the tegument, in countries like the cervix, cubitus, carpus, facial nervousnesss. The posterior tibial nervus is the most normally affected nervus followed by the ulnar, average and sidelong popliteal and facial nervousnesss. It is the harm to these nervousnesss that cause some of the symptoms of leprosy such as motor and centripetal loss. Attack of the little cuticular nervousnesss can take to hypoaesthesia and anhydrosis in borderline-tuberculoid and tuberculoid lesions. Within lepromatous disease baseball mitt and carrying centripetal loss occurs alternatively.

Eye Damage – Leprosy can do harm to the oculus by doing nervus harm and from the bacteriums occupying the oculus. Surveies have shown that 2.8 % of patients with multibacillary Hansen’s diseases were blind when diagnosed with leprosy and a farther 11 % had potentially blinding pathology. This can be potentially lay waste toing if the patient has nerve harm that has caused anaesthia in the custodies and pess.

Immulogical Chemical reaction

There are two types of Immulogical reactions associated with leprosy, type 1 ( reversal ) or type 2 ( erythema nodosum leprosum [ ENL ] ) . Around a 3rd of patients that have borderline Hansen’s disease can hold type 1 reactions while 50 % of those who suffer from lepromatous signifier and 10 % of boundary line Hansen’s disease are affected by type 2 reactions. However these reactions can happen at any clip and may be a reaction to the bacteria or the multidrug therapy ( during or after intervention ) .

Our patient is enduring from type 2 reactions or ENL, which is typically associated with febrility, unease, painful redness of the nervousnesss and the visual aspect of new nodules. These nodules are typically hypodermic, erythematous and painful for the patient. They are typically found on the face and limbs, but can be found on any portion of the organic structure.

ENL is thought to be an immune composite disease which accordingly activated the compliment immune response ; there are besides elevated degrees on TNF-I± and interferon-I? within the patients system. Widespread immune complex deposition can happen and this can take to farther complications to the patient including polyarthritis, lymphadenitis and iridocyclitis.

Treatment of Hansen ‘s Disease

Early interventions of leprosy were chiefly down to test and mistake and many compounds were indicated for usage that would non be considered today. These include anilin dyes, Sb, arsenic, baths, Cu, electrical currents, K iodide, Ra, sera, strychnine, thyme camphor, vaccinums and X raies. However one of the major interventions throughout the late 19th and early twentieth centuries was chaulmoogra oil, which was assorted with lard and was applied locally or taken orally. The merchandise so became commercially in 1909 available from Bayer and Company and Winthrop Chemical Company under the trade names Antileprol and Chaulmestrol severally. However these interventions have all been superseded by newer interventions which are listed below, most of the interventions used being antibiotics.


Part of the sulfones, Dapsone is normally considered one of the foundations of intervention of Hansen’s disease. Dapsone exerts in antibacterial action against M. Leprae by the indirect decrease in folic acid through the suppression of dihydropteroate synthase. In one mouse foot-pad theoretical account unwritten therapy of dapsone saw a decrease in the figure of feasible beings by 99.4 % which was apparent by the slowdown in growing curves between dapsone treated versus the control group. The dosage of dapsone is normally 100mg once/day orally with no accommodation needed with patients with nephritic damage, nevertheless for those with hepatic damage ; nevertheless no guidelines exist on dose accommodation for hepatic damage.

Dapsone was originally used in monotherapy of leprosy but opposition became debatable, estimated at 2-10 % . It has been proposed that the mutant of the folP1 cistron taking to a more immune dihydopteroate synthase which is capable of synthesizing folic acid in more utmost conditions. Due to resistance expected with monotherapy, multidrug therapy has now become the criterion for attention.

Dapsone has been associated with methemoglobinemia, hemolysis, lymphadenopathy, fever, hepatitis, leucopenia, anemia, acute psychosis and seldom peripheral neuropathy. These inauspicious effects can be restricting to intervention nevertheless the most profound side effects being methemoglobinemia and hemolysis linked to a lack in glucose-6-phosphate dehydrogenase ( G6PD ) . Dapsone can be used in gestation nevertheless cautiousness should be used as it is possible harmful to the fetus, harmonizing to FDA categorizations it is a category C drug. It is besides excreted through chest milk and can be potentially harmful to babes that have a reduced degree of G6PD who are breast Federal.


Rifampicin is a disinfectant agent that acts by adhering to the I?-subunit of RNA polymerase and block written text of RNA and its activity is seen in even slow spliting cells such as M. leprae. Bactericidal success can be seen within 3 hebdomads of therapy and even a individual dosage has been shown to be effectual in cut downing the bacterial burden. Rifampicin can be taken monthly or day-to-day depending if the patient is to be supervised or non, it is besides available as I.V. extract but this signifier of intervention is seldom used. Patients with hepatic disfunction do non necessitate a decrease in dose nevertheless for those who have nephritic damage with creatinine clearance below 10ml/min should hold a 50 % decrease in dosage. Rifampicin should merely be used in multidrug therapy due to the rapid visual aspect of opposition ; this is likely due to mutants in the I?-subunit of RNA polymerase through point mutants in ropB cistron.

Side effects of rifampicin include unease, roseola and hepatotoxity. Warning should be given about the fact piss, perspiration and cryings can hold orange stain and this may do hurt to the patient and may do have oning contact lenses uncomfortable but it does non intend the drug should be withheld. However if the patient develops thrombocytopenia, a rare side consequence, rifampicin should be discontinued instantly and another intervention should be initiated. There are many interactions with rifampicin and patient ‘s medicine should be checked before originating intervention. Dapsone metamorphosis is increased by rifampicin but it is non considered of import in the intervention of Leprosy, but Pediapred, used in the intervention of type 1 and 2 reactions, has a important interaction. Due to this interaction if Pediapred needs to be introduced into therapy the rifampicin dosage should be reduced from a upper limit of 600mg/day to 600mg/month. Rifampicin is rated by the FDA as a category C drug in gestation and therefore should be used with some cautiousness nevertheless it is non teterogenic, it besides excreted through chest milk.


A phenazine dye that has a similar antibacterial activity as Dapsone, clofazine is utile in dapsone opposition as it is still active in strains resistant to dapsone intervention. Its method of action is non understood but its ability to adhere to DNA of M. Leprae may be linked to its activity. There are some suggestions that cloafimine as the added benefit of being immunomodulatory and this may which can be utile if the patient is likely to endure either a type 1 or type 2 reaction. The usual dosage of clofazine is 300mg monthly under supervising, and 50mg daily supervised ( or 100mg on alternate yearss ) . However in the instance of an immune reaction clofazimine dosage can be increased up to 300mg daily for a upper limit of 3 months ; nevertheless it may take up to 6 hebdomads before they have maximal curative consequence.

Side effects are comparatively mild in comparing to the some of the other medicines used to handle leprosy with the chief 1s being sickness and emesis, abdominal hurting and tegument stain. Most of the stain manifests itself as additions pigmentation on the tegument due to increased degrees of melanin, this can prevail after intervention but chiefly the stain fades one time intervention has been withheld. Since clofazimine can be excreted though cryings patients should be warned that contact lenses may go stained when used during intervention. One issue with clofazime in the UK is down to its handiness merely on a named patient footing which may increase the clip a patient has to wait before intervention can get down.


Fluoroquinolones, such as moxifloxacin and ofloxacin, act by suppressing DNA gyrase and DNA reproduction and written text in M. Leprae. Antibacterial drugs like moxifloxacin have a similar bactericidal activity to rifampin with one dosage bring forthing a significant decrease in bacterial burden. In one survey after three hebdomads of day-to-day intervention there were no feasible beings staying. Ofloxacin besides has substainal activity and is used in the intervention for individual lesions along with a combination of other drugs. However the other drugs in this category have small activity against the bacteria and should be avoided in intervention. Resistance to this category of drug occurs chiefly due to mutants in the gyrA but non through gyrB.


Minocycline is a tetracycline antibiotic that exerts its consequence on the 30S ribosomal fractional monetary unit in M. Leprae. It is non every bit active as Rifadin, nevertheless it is still considered a utile option in intervention of Leprosy due to resistance, intolerance or clinical failure. There are inauspicious effects in utilizing long term intervention of Minocin, including skin pigmentation, g.i. annoyance and cardinal nervous system effects. It should be avoided in gestation due to its ability to stain enamel.


Clarithromycin is a man-made macrolide that has better antibiotic activity than the remainder of the macrolides but has reduced activity against Minocin. It is thought that it acts by the decrease of ATP and is utile as an option to therapy where there is intolerance or opposition.

Treatment of Immunological Reactions

These types of reactions are medical exigencies that must be treated every bit shortly as possible to guarantee that there are no long term effects on the patient. Antibacterial therapy should be continued throughout these reactions because the benefits of intervention outweigh the hazard. There are several options for intervention that each has their ain benefits and hazards associated with them. Type 2 reactions or ENL is hard to handle and so many options need to be considered


Corticosteroids are used to supply diagnostic alleviation from immune responses and work good for type 1 reactions. Initiation therapy of 40-60mg of prednisolone day-to-day can be used to supply this alleviation. Treatment length should be kept every bit short as possible to cut down the hazard of developing the long term effects associated with steroid usage nevertheless these effects should be weighed against the patients risk if they do non have steroids. When used to handle ENL it has been found that perennial classs of corticoids may be required due to the difficultly in supplying sustained alleviation.


Thalidomide is a utile drug in the intervention of ENL and has been shown to be more effectual at supplying alleviation than corticoids and should be considered if the patient is corticosteroid intervention does non supply alleviation to ENL symptoms or if they are contraindicated. Its method of action is non to the full understood, but it has been shown to cut down the degrees of TNF-I± . Through the ADF evaluation system thalidomide is a category X drug and therefore it should usually be avoided in female patients who are or who may go pregnant. Treatment of these patients with thalidomide should non be taken lightly and the patient needs to portion of the determination doing procedure before get downing intervention.


Pentoxifylline has been shown to diminish degrees of TNF-I± in patients through an unknown mechanism when a dosage of 400-800mg three times daily. However it does non execute every bit good as thalidomide in a randomised clinical test. There is a usage for it though when thalidomide is contraindicated or uneffective, as 62.5 % of patients having intervention experient alleviation in their symptoms. The major inauspicious effects with this drug include g.i. jobs and CNS jobs nevertheless by utilizing controlled-release preparations there are decreases in side effects.

Tumor necrosis factor inhibitors

Working on the footing that many of the drugs listed above cut down degrees of TNF-I± systemically utilizing biologic TNF inhibitors for the intervention of ENL reactions would be a logical measure. It has been shown in surveies that utilizing biologics like Enbrel and Remicade can be used to handle more serious and hard to handle reactions, nevertheless they should be used with cautiousness as the biologics are besides known the aggravate infections and studies have besides been published demoing Remicade and adalimumab addition the bacterial burden within patients. Therefore any determination on whether to get down intervention should be based upon the badness of the reaction.

Recommendation for intervention

Our patient is a 25 twelvemonth old female with multibacillary Hansen ‘s disease, with a terrible type II reaction. Initially I ‘d urge that the intervention of Hansen’s disease is continued due to the wellness hazards associated by keep backing intervention is excessively great. The combination I would urge is Dapsone 100mg daily ( unsupervised ) , Rifampicin 600mg monthly ( supervised ) and Clofazimine 300mg daily for 3 months to assist cut down the badness of the ENL reactions, after 3 months this so needs to be reduced back down to 50mg day-to-day plus 300mg monthly. To assist with the terrible ENL reactions I would besides urge adding on Prednisolone 60mg to assist alleviate symptoms, retreating intervention every bit shortly as clinically possible, repetition classs may be required. If farther intervention is required to supply alleviation so I would urge adding in Pentoxifylline 400mg daily.