Case Report

MORBUS HANSEN
By:

Alqi Yutha Rahmi Hayati

Supervisor: Vella

DERMATO-VENEOROLOGY DEPARTMENT SCHOOL OF MEDICINE SYIAH KUALA UNIVERSITY Dr. ZAINOEL ABIDIN GENERAL HOSPITAL BANDA ACEH September 2013

Introduction Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It is an acid fast bacillus that replicates slowly (generation time 13 days). M. lepraesecretes no toxins, and its virulence is based on properties of its cell wall. It grows optimally at <37 C, explaining the bacteriums tendency to infect the cool areas of the body, such as the skin and the nerves close to the skin. The invading bacteria have three specific targets: peripheral neural tissue (Schwann cells), small vessels (endothelial cells and pericytes), and the monocyte-macrophage system. The formation of granulomas is a common histopathologic landmark of disease1. Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and its accompanying immunologic events, but whose course and sequelae often extend many years beyond the cure of the infection and may have severely debilitating physical, social, and psychological consequences. Both aspects must be considered by clinicians, researchers, and policymakers who deal with persons affected by this disease4. Leprosy can manifest in different forms, depending on the host response to the organism. Individuals who have a vigorous cellular immune response to M leprae have the tuberculoid form of the disease that usually involves the skin and peripheral nerves. The number of skin lesions is limited, and they tend to be dry and hypoesthetic. Nerve involvement is usually asymmetric. This form of the disease is also referred to as paucibacillary leprosy because of the low number of bacteria in the skin lesions (ie, < 5 skin lesions, with absence of organisms on smear). Results of skin tests with antigen from killed organisms are positive in these individuals3. Patients may also present with features of both categories; however, over time, they usually evolve to one or the other (indeterminate or borderline leprosy). Classification of leprosy: Leprosy has 2 classification schemas: the 5-category Ridley-Jopling system and the simpler and more commonly used WHO standard.

Ridley-Joplings classification depending on the host response to the organism, leprosy can manifest clinically along a spectrum bounded by the tuberculoid and lepromatous forms of the disease. Most patients fall into the intermediate classifications, which include borderline tuberculoid leprosy, midborderline leprosy, and borderline lepromatous leprosy. The classification of the disease typically changes as it evolves during its progression or management. The Ridley-Jopling system is used globally and forms the basis of clinical studies of leprosy. It may also be more useful in guiding treatment regimens and assessing risk of acute complications. Physical findings in each subtype are presented in the Clinical section. The clinical pattern depends on the ability of the body to mount an immune response to the invading bacilli6,7. According to the WHO, a patient with Leprosy is defined as having one or more of the following features, and who has yet to complete a full course treatment : 1) hypopigmented or reddish skin lesion(s) with definite loss of sensation, 2) involment of peripheral nerves, as demonstrated by definite thickening with loss of sensation, 3) skin smear positive for acid-fast bacilli. WHO classification divides cases into 3 types : paucibacilarry single-lesion (1 lesion), paucibacillary (2-5 lesions), and multibacillary (more than 5 lesions)8. Skin lesions may be multiple (border line) or innumerable (lepromatous). In the lepromatous form lesions may be bilaterally symmetrical and ill defined macules or diffuse infiltration that may progress to formation of plaque & nodules. In addition, there may be nasal bleeding & oedema of both feet. In the absence of treatment, paucibacillary form of leprosy may downgrade to multibacillary (from tuberculoid to lepromatous) through borderline spectrum5. Leprosy reactions are the acute episodes of clinical inflammation occurring during the chronic course of disease. They pose a challenging problem because they increase morbidity due to nerve damage even after the completion of treatment. They are classified as type I (reversal reaction; RR) or type II (erythema nodosum leprosum; ENL) reactions. Type I reaction occurs in borderline patients (BT, midborderline and BL) whereas ENL only occurs in BL and LL forms. Reactions are interpreted as a shift in patients immunologic status. Chemotherapy, pregnancy, concurrent infections, and emotional and physical

stress have been identified as predisposing conditions to reactions . Both types of reactions have been found to cause neuritis, representing the primary cause of irreversible deformities7. We report a case of lepromatous or Multibacillary Leprosy to enhance our knowledge about current epidemiology, classification system, diagnosis, and treatment, as well as the prevention of disability that would occurred by leprosy

CASE REPORT Patient Identity Name Sex Medical Record Age Race Address Examination date Anamnesis 1. The Chief Complaint Pain and red rash felt over all of the body since a year ago. 2. Additional Complaint Fever and joint pain 3. History of Present Illness A 45 years old female presented to us with multiple painful reddish thickening lesions over the arms, forearms, legs, boy, and facial associated with high grade fever and severe constitutional symptoms for a years. At the first time te red rash is a flat lesions and then progress to tickening since a year ago and her eyebrow kept loss since 1 year ago. The patient told that she could not feel the lesion, when she touch or prick the lesion,its just like : Mrs. K : Female : 96-75-19 : 45 years old : Aceh : Kutacane : September 4th 2013

nothing happened such a sensorium lost. Patient also had

multiple skin

coloured raised swellings over bilateral ear lobes for 1 year . The patients was apparently well 1 year back when he developed skin coloured

asymptomatic swellings over the ear lobes which were initially pin head sized but gradually progressed to lentil size. Patient also complained about abnormally dry skin on her leg and pain in the wrist, elbow, ankle, and knee joint for 1 year. Edema in her feet was complained as well for 10 months. The patient had done Multy Drug Treatment for a month and drop out for the next month. 4. History of Past Illness None 5. Family History None of her family had this kind of disease. 6. History of Medicine The patient had done multy drug treatment for a month and no medication on the next month due to limitation of MDT. 7. Social History The patient told us that she dont know about other leprosy case in her region and she has no idea if she had contact with another leprosy patient or not

A. Physical Examination Vital sign General Condition Abnormal Finding : Not checked : Fatigue :

Madarosis (+) / (+) Xerosis at region: cruris dextra et sinistra (+) / (+) antebrachii dextra et sinistra (+) /(+) Ulnaris nerve sinistra thickening (+)

Dermatologic status : Location :

a/r facialis, thoracalis anterior et posterior, Abdomen, and superior extremity dextra et sinistra, inferior extremity dextra et sinistra Significant finding : erythematous plaque, well-defined with irregular margination,multiple lesion with nummular to plaque. Generalisata distribution.

A Figure 1. Lesions at face and back

(A).Regio facialis : Multiple Macules erythematous, plaque size, > 5 lesions (B) Regio Coli and thorakal posterior : Multiple macules erythematous, numular to plaque size, > 5 lesions

Figure 2. Antebrachii and Cruris Region (A) Erythematous macules,anaesthesia, plaque size. Xerosis positive (B) Xerosis positive, dorsum edema covered with squamous B. Diagnosis of Appeals MB Leprosy + Type 2 Reaction DD/. 1. Psoriasis Vulgaris 2.Tinea Corporis 3. Drug Eruption C. Supporting Examination Sensibility test : Sensibility lost on the lessions Facialis Region (+) Coli Region (+) Brachii et Antebrachii region (+) / (+) Cruris region (+) / (+) Peripheral nerve enlargement - Auricularis magnus enlargement : (-) / (-) - Ulnars nerve enlargement : (+) / (-) - Tibial posterior nerve enlargement : (-) / (-) - Poplitea nerve enlargement : (-) / (-) Slit-Skin smear BI : +1 MI : 60%

D. Diagnosis MB Leprosy + Reaction type 2 E. Procedures 1. Treatment a. Supportif - Bed rest b. Pharmacology Systemic : Day 1 : 2 capsul rifampicin @300 mg (600 mg) 3 capsul Lamprene @100 mg (300 mg)

1 tablet dapsone @100 mg Day 2-28 : 1 capsul Lamprene @50 mg 1 tablet dapsone @100 mg Aspirin 4x400mg Full course of treatment 12 months

2. Education - Leprosy is a chronic bacterial infection. This disease is very harmful if not treated well - Leprosy is curable but if untreated can lead to severe deformities. - Explaining side effect of the drug. Rifampisin Dapson Lampren : reddish urine. : Anemia : Darker Skin colour

- Do not scratch the lesion. F. Prognosis - Quo ad vitam - Quo ad functionam - Quo ad sanactionam : dubia ad bonam : dubia ad bonam : dubia ad bonam

Discussion In this case, we have established the diagnosed based on history taking, physical diagnostics, significant dermatology findings and other dermatology examinations to support our suspicion that patient may have leprosy. We also did the test for leprosy based on that 3 cardinal sign of leprosy and we found that patient have some loss of skin sensation at face, upper and lower extremity. The patien also have ulnar nerve sinistra enlargement on palpation. The diagnosis of leprosy is based on the 3 cardinal sign of the disease, which are : skin patch with loss of sensation; enlarged peripheral nerve; positive slit-skin smear. Based on all finding and literature, we established that patient have multibacillary leprosy with reaction type 2.

According to WHO classification, multibacillary leprosy defined as leprosy with more than 5 lesions and as it correlation with Ridley-Jopling classification, multibacillary leprosy consist of some BT, BB, BL, and LL7. Individuals with minimal cellular immune response have the lepromatous form of the disease or multibacillary, which is characterized by extensive skin involvement. Skin lesions are often described as infiltrated nodules and plaques, and nerve involvement tends to be symmetric in distribution. The organism grows best at 27-30C; therefore, skin lesions tend to develop in the cooler areas of the body, with sparing of the groin, axilla, and scalp. This form of the disease is also referred to as multibacillary leprosy because of the large number of bacteria found in the lesions (ie, >6 lesions, with possible visualization of bacilli on smear)3. Pathogenesis of type II reaction is thought to be related to the deposition of immune complexes. Increased levels of TNF-, IL-1, IFN-, and other cytokines in type II reactions are observed. In addition, C-reactive protein, amyloid A protein, and -1 antitrypsin have also been reported to be elevated in ENL patients sera. A massive infiltrate of polymorphonuclear cells (PMN) in the lesions is only observed during ENL and some patients present with high numbers of neutrophils in the blood as well. Neutrophils may contribute to the bulk of TNF production that is associated with tissue damage in leprosy. More recently, microarray analysis demonstrated that the mechanism of neutrophil recruitment in ENL involves the enhanced expression of E-selectin and IL-1, likely leading to neutrophil adhesion to endothelial cells; again, an effect of thalidomide on PMN function was observed since this drug inhibited the neutrophil recruitment pathway. Altogether, the data highlight some of the possible mechanisms for thalidomides efficacy in treating type II reaction. TNF- may augment the immune response towards the elimination of the pathogen and/or mediate the pathologic manifestations of the disease. TNF- can be induced following stimulation of cells with total, or components of M. leprae, namely, lipoarabinomannan (the mycobacteria lipopolysaccharide- like component) a potent TNF inducer. In addition, mycolyl-arabinogalactan-peptidoglycan complex

ofMycobacterium species, the protein-peptidoglycan complex, and muramyl dipeptide all elicit significant TNF- release7. As the result of the anamneses, we found the patient presented with multiple painful reddish thickening lesions over the arms, forearms, legs, body, and facial associated with high grade fever and severe constitutional symptoms for a years. At the first time the red rash is a flat lesions and then progress to tickening since a year ago and her eyebrows kept losing since a year ago.. The patient told that she could not feel the lesion, when she touch or prick the lesion,its just like nothing happened such a sensorium lost. Patient also had multiple skin coloured raised swellings over bilateral ear lobes for 1 year . The patients was apparently well 1 year back when he developed skin coloured asymptomatic swellings over the ear lobes which were initially pin head sized but gradually progressed to lentil size. Patient also complained about abnormally dry skin on her leg and pain in the wrist, elbow, ankle, and knee joint for 1 year. Edema in her feet was complained as well for 10 months. As explained in the literature, the invading bacteria have three specific targets: peripheral neural tissue (Schwann cells), small vessels (endothelial cells and pericytes), and the monocyte-macrophage system. The formation of granulomas is a common histopathologic landmark of disease1. Leprosy is essentially a disease of peripheral nerves but it also affect the skin and sometimes certain other tissues, notably the eye, the mucosa of the upper respiratory tract, muscle, bone and testes2. Madarosis or loss of eyebrows is caused by bacillary infiltration/follicle destruction. On slit-skin biopsy, we found that bacterial (BI) at +1 and morphologic index at 60%. As the literatures said that test for leprosy include serologic assays, slit-skin smears, biopsies, be probes, polymerase chain reaction (PCR), and the lepromin test7. Slit-skin smears provide both bacteriologic indice (ie, measurement of the bacterial load) as well as morphologic indices, which signify viability. The inability to detect bacilli places a case in the paucibacillary categories (intermediate and tubercoloid tubercoloid). The demonstration of bacilli defines it as multibacillary (borderline tubercoloid, borderline borderline, and leprotamous). Unfortunetly, 70% of patients have negative smears; by

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definition, paucibacillary leprosy lack evidence of bacilli. In endemic areas, diagnosis may be made without biopsy, in part because the correlation between the clinical diagnosis and histopatologi is low. The lepromin test gauges the patients cell-mediated immune response to Mycobacterium leprae. The result is negative in lepromatous leprosy and positive in tubercoloid leprosy. Because the lepromin test in negative in lepromatous, it cannot be used to diagnose or confirm leprosy reliably, but it can assist in classification of recognized cases7. In general principles of management patient with leprosy include 6 steps :6 1. Eradicate infection with antilepromatous therapy. 2. Prevent and treat reactions. 3. Reduce the risk of nerve damage. 4. Educate patient to deal with neuropathy and anesthesia. 5. Treat complications of nerve damage. 6. Rehabilitate patient into society.

The patient treated with Multy Drug Treatment (MDT) Multibacillary. Patient had done a month MDT, so for for the next therapy only need 11 pack MDT MB for 11 month (1 pack per 4 week). The treatment consist of, Day 1: 2 capsul rifampicin @300 mg (600 mg), 3 capsul Lamprene @100 mg (300 mg), 1 tablet dapsone @100 mg. Day 2- 28 : 1 capsul Lamprene @50 mg, 1 tablet dapsone @100 mg. Makin the initial diagnosis of leprosy can be a challenge, may be the treatment : leprosy requires years of treatment and even more years of follow-up, complicated by reactional states. Leprosy was previously treated with monotherapy, suh as dapsone or rifampisin. Monotherpy, however, lead to drug resistance. Multidrug therapy was introduced by the WHO in 1982 and include use of dapsone, rifampin, and clofazimine8. Dapsone, which is bacteriostatic or weakly bactericidal against M. leprae, was the mainly treatment for leprosy for many years until widespread resistant strains appeared. Combination therapy has become essential to slow the development of resistance. Rifampicin is now combine with dapsone to treat paucibacillary leprosy. Rifampicine and clofazimine are now combine with dapsone to treat multibacillary leprosy. Any patient with a positive skin smear must be treated with the MDT regimen for

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multibacillary leprosy. The regimen for paucibacillary leprosy should never be given to a patient with multibacillary leprosy. Therefore, if the diagnosis in a particular patient is uncertain, treat that patient with MDT regimen for multibcillary leprosy10.

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Refferences 1. Kattan, JA. 2006. The Epidemiology and Clinical Presentation of Leprosy in Pediatric Population of Paraguay. Thesis. Yale University School of Medicine. 2. Bryceson, A., Pfaltzgraff, R. 1990. Leprosy for Student of Medicine. Medical Division of Longman group UK Limited 3. WHO. Weekly Epidemiological Record. 2011 86: 389-400 4. Scollard, DM et al. The Continuing Challenge of Leprosy. Clinical Microbiology Reviews. 2006 19 : 338381. 5. NLEP. 2009. Training Manual for Medical Officer. Ministry of Health and Family Welfare. New Delhi 6. Departement of Health and Famillies. 2010. Guidline for the Control of Leprosy In Northen Territory. Northen Territory Government 7. Bhat, RM., Prakash,C. 2012. Leprosy: An Overview Pathopysiology. Hindawi Publishing Corporation. 8. Wolff, K. Jonhson,R. Allen. 2009. Fitzpatricks Colour Atlas and Synopsis of Clinical Dermatology 6th edn; 24:665. McGraw-Hill. 9. Wolff, K. et al. 2008. Fitzpatriks Dermatology in General Medicine: Cutaneous Reaction to Drug- 7th Edition; 186:1786. McGraw-Hill. 10. WHO. 2013. Leprosy Elimination : WHO Multy Drug Therapy (MDT). Available at http://www.who.int/lep/mdt/en/index.html [Accessed : September 6th 2013]

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