Peripheral Smear And Complete Hemogram
Dissertation submitted in
Partial fulfillment of the requirements for the award of
M.D. DEGREE in
PATHOLOGY – BRANCH III REGISTER NO : 201713502
THE TAMILNADU
DR. M.G.R. MEDICAL UNIVERSITY CHENNAI - 32
OCTOBER 2019
This is to certify that the dissertation entitled “Observational Study of Cases of Lepra Reactions By Peripheral Smear And Complete Hemogram”
is a record of bonafide work done by Dr. Nisha. K in the Department of Pathology, Chengalpattu Medical College, Chengalpattu under the supervision of Dr. S. Ravi M.D., Professor and Head, Department of Pathology and submitted in partial fulfillment of the requirements for the award of M.D. Degree in Pathology by The Tamilnadu Dr. MGR Medical University, Chennai. This work has not formed the basis for the award of a degree or diploma, any time before.
Dr. Hariharan,M.S.,Mch., Dr. S. Ravi M.D.
Dean, Professor and Head,
Chengalpattu Medical College, Department of pathology, Chengalpattu Chengalpattu medical college Chengalpattu
I hereby declare that the dissertation entitled “Observational Study of Cases of Lepra Reaction By Peripheral Smear And Complete Hemogram
”
was done by me in the Department of Pathology, Chengalpattu Medical College, in collaboration with, Central Leprosy Teaching And Research Institute, Chengalpattu from May 2017 to October 2019,under the guidance and supervision of Dr. M. Sivakami M.D., Associate Professor, Department of Pathology, Chengalpattu Medical College.
This dissertation is submitted to the Tamil Nadu Dr.MGR Medical University, Chennai towards the partial fulfillment of the requirements for the award of M.D. Degree in Pathology.
I have not submitted this dissertation on any previous occasion to any University for the award of any degree.
Place:
Date: Nisha. K
This is to certify that the dissertation entitled, “Observational Study of Cases of Lepra Reactions By Peripheral Smear And Complete Hemogram”
submitted by the candidate Dr. Nisha. K in partial fulfillment of the requirements for the award of M.D. Degree in Pathology by The Tamil Nadu Dr. M.G.R. Medical University, Chennai is a bonafide research work done by her under my direct guidance and supervision, in the Department of Pathology, Chengalpattu Medical College, Chengalpattu. This work has not formed the basis for the award of any degree or diploma, any time before.
Dr. M. Sivakami.,MD.
Associate Professor Department of Pathology,
Chengalpattu Medical College, Chengalpattu
COMMITTEE CERTIFICATE
To start with, I thank the almighty GOD in making this project a successful one.
I express my deep gratitude to Dr. Hariharan M.S., Mch Dean, Chengalpattu Medical College, for granting me permission to undertake this study.
I profusely thank and express my sincere gratitude to Dr. S. Ravi M.D., Professor and Head, Department of Pathology, Chengalpattu Medical College, for having suggested this topic for dissertation and for having rendered his valuable support and encouragement without which this project work would not have been feasible.
I wish to record my heartfelt thanks to Dr. M. Sivakami M.D., my guide for being always with me to motivate me and who spared her valuable time to make this work come out in the best possible way.
I wish to extend my sincere thanks to Dr. Chitrakala Sugumar M.D, DGO., Dr. Saravanan, M.D., Dr. Vanitha,M.D., Associate Professors, Department of Pathology, Chengalpattu Medical College, for their constant support and encouragement throughout my work.
I more than indebted to my previous associate professors Dr. Surekha MD., Dr. Sheeba M.D., Dr. Sathyalakshmi M.D, Dch for the words of support and encouragement when I embarked on this project.
I also wish to record my sincere thanks to Dr. S. Suryalakshmi, MD., Dr. V. Palaniappan, MD., Dr. M. Malathi, MD., Dr. D. Pushpalatha, MD., Dr. Prathipa. MD., Dr. Mahesh, MD, Dr. P.S. Vamitha, MD, Assistant Professors in Department of Pathology, Chengalpattu Medical College, for their constant support and encouragement throughout my work.
Leprosy Teaching and Research Institute for granting me permission to do this study at the institute.
I thank all the technical staff in the Department of Pathology, Chengalpattu Medical College, for their sincere and timely technical assistance.
I dedicate this book to my sister, Rosana. K, who was always there to cheer me up during the difficult times.
Last but not the least, I am indebted to all the patients who have made this study possible.
Dr. Nisha. K
SL. NO PARTICULARS PAGE NO.
1 Introduction 1
2 Aims and Objectives 2
3 Review of Literature 3
4 Materials and Methods 33
5 Observation and Results 40
6 Discussion 65
7 Conclusion 68
8 Bibliography 70
9 Annexures
I: Proforma II: Master chart
III: Glossary
Sl.No. TITLE Page No 1 Various haematological parameters in Type I lepra
reaction
37
2 Various haematological parameters in Type II lepra reaction
38
3 p value estimation 39
4 Distribution of lepra reaction among different age groups
40
5 Distribution of lepra reaction among different sexes 42 6 Incidence of lepra reaction along the different
spectrum of leprosy
43 7 Onset of reaction in relationship to MDT 45 8 Peripheral smear picture in lepra reaction 59
Sl.No. Title Page no 1 Distribution of reaction among different age groups –
Pie chart
41
2 Distribution of reaction among different sexes – Pie chart
42
3 Incidence of different types of lepra reaction
occurring along the spectrum of leprosy – Bar chart
44
4 Onset of reaction in relationship to MDT – Bar chart 45 5 RBC counts in different cases of lepra reaction – Bar
chart
46
6 WBC counts in different cases of lepra reaction – Bar chart
47
7 Hb levels in different cases of lepra reaction – Bar chart
48
8 PCV in different cases of lepra reaction – Bar chart 49 9 MCV in different cases of lepra reaction – Bar chart 50 10 MCH in different cases of lepra reaction – Bar chart 51 11 MCHC in different cases of lepra reaction – Bar
chart
52
Bar chart
13 Neutrophil count in different cases of lepra reaction – Bar chart
54
14 Lymphocyte count in different cases of lepra reaction – Bar chart
55
15 Mixed cell population count in lepra reaction 56 15 RDW in different cases of lepra reaction – Bar chart 57 16 Reticulocyte count in different cases of lepra reaction
– Bar chart
58
Sl.No. TITLE Page No.
1 HPE picture of tuberculoid leprosy 60
2 HPE picture of borderline tuberculoid leprosy 60
3 HPE picture of borderline lepromatous leprosy 61
4 HPE picture of lepromatous leprosy 61
5 HPE picture of erythema nodosum leprosum 62
6 Peripheral smear of microcytic anaemia 63 7 Peripheral smear of macrocytic anaemia 63
8 Peripheral smear of neutrophilia 64
INTRODUCTION
Leprosy, caused by Mycobacterium leprae, is a chronic granulomatous disease with predilection for affecting skin and nerves. It is also called as Hansen’s disease as a tribute to the Norwegian physician Gerhard Henrik Armauer Hansen, who first described the bacillus. The main mode of transmission is through aerosolized droplets from the infected patient. Because of the variation in the immune response mounted by each individual, they may present with a wide range of symptoms, from very mild cutaneous manifestations to those due to severe lepra reactions. Lepra reactions stand to be the greatest cause of morbidity, disability and ensuing social stigma in leprosy patients. They present as an acute episode that interrupts the slow and chronic evolution of leprosy. The hematologic findings in lepra reactions are few in the literature most of which elaborate on the disorders of coagulation and fibrinolysis. This thesis is an attempt to study the haematological and peripheral smear findings in lepra reaction to understand the possible mechanism and suggest therapy for its complications.
AIMS AND OBJECTIVES
1. To evaluate the complete hemogram findings in cases of lepra reaction.
2. To find out proportion of lepra reaction cases developing anemia.
3. To find out the type of anemia, developing in lepra reactions.
4. To find out the proportion of lepra reaction cases, with elevated reticulocyte count.
REVIEW OF LITERATURE
DEFINITION OF LEPRA REACTION:
The term reaction has been given to those episodes of significant inflammation which are a consequence of the mycobacterium leprae bacilli directly itself and not those as a result of any secondary infection or trauma1 CLASSIFICATION OF LEPRA REACTION:
Classification of the patients is necessary to decide on the appropriate treatment. It helps the clinician to predict those patients who are likely to develop complications and to give an accurate prognosis. Two systems used to classify leprosy patients.
1) The Ridley–Jopling system 2 – It is based on clinical and histopathological features and the bacteriological index. The categorisation is based on the immune response mounted by the patient’s immune system in response to the bacilli.
a) Type I lepra reaction - Downgrading reaction - Upgrading reaction b) Type II lepra reaction
c) Type III lepra reaction
2) WHO operational system3 – It is based on the number of lesions and is used when facilities for slit-skin smears are not available. It is simple tool that can be used even by the health care providers.
SYNONYMS FOR DIFFERENT REACTIONS IN LEPROSY 1. Acute exacerbations in leprosy (Dharmendra)
2. Leprosy reaction (Jopling W.H)
3. Acute phases in leprosy (Cochrane R.G.) 4. Lepra reaction (Muir.E)
5. Type I reaction (Bryceson) a) Borderline reaction b) Tuberculoid reaction
c) Non lepromatous lepra reaction 6. Type II reaction
a) ENL reaction
b) Lepra fever (Ramu and Dharmendra) c) Lepromatous lepra reaction (Bryceson)
7. Reversal reaction – upgrading reaction 8. Type II reaction – Lucio Phenomenon
LEPROSY TYPE NO OF SKIN LESIONS Paucibacillary 1-5
Multibacillary 6 or more
EPIDEMIOLOGY PREVALENCE:
Type I reactions: Type 1 reactions (T1R) develop in around 30% of patients and are seen in the immunologically unstable borderline forms of leprosy4. Type II reactions: Type 2 reactions develop in around 19- 26% of the patients and are seen in BL and LL cases5.
AGE:
The common age group of presentation of Type I and Type II reactions is between 20-40 years, with the highest incidence of type II reaction being noted between 11-40 years, which corresponds to the highest age of incidence at which leprosy in detected in South India 6. A higher prevalence of leprosy has been noted in children. Most of them tend to have either indeterminate or tuberculoid type of leprosy7. Even with such high prevalence rates, the frequency with which the type I and type II reactions occurs in children is extremely rare.
SEX:
Type I and Type II reactions are seen to occur in both the sexes with an almost equal frequency. Studies carried in South India8 show a predominance of males6 presenting with type II lepra reactions and this was due to the increased number of male patients reporting to the hospital (10:1). Studies by Browne 9 show a higher incidence among males whereas those by Guinto10 showed them to be more among females.
TYPE OF LEPROSY
Type of reaction and the class of leprosy associated with it
Al types of leprosy can show some manifestation of reactions except that of indeterminate leprosy.
TYPE I LEPRA REACTION:
It is an example of delayed type of hypersensitivity reaction. It is seen in both borderline as well as tuberculoid leprosy patients who are on treatment who are on treatment or following the completion of multi drug therapy11. Sometimes the disease manifests itself for the first time as reaction and persists for long periods of time12. Type 1 reaction is usually a reversible reaction otherwise called upgrading reaction or the false exacerbation reaction. The other subtype is usually associated with worsening and called the downgrading reaction13.
TYPE II LEPRA REACTION:
Also called erythema nodosum leprosum. It is an example of type III hypersensitivity reaction. It is seen in multibacillary leprosy cases with a high
TT BT BB BL LL
ENL
Downgrading reaction
Upgrading Reaction
bacillary load as in cases of borderline lepromatous and lepromatous leprosy patients12. Type 2 reactions are more severe than type 1 reactions are they present with systemic manifestations and due to their recurring nature14
TYPE III LEPRA REACTION
Also called Lucio phenomenon. It is a variant of Type 2 reaction and is observed in cases of diffuse lepromatous leprosy (DLL or Lucio-Latapí leprosy).
This particular variant of lepromatous leprosy (LL) is reported mainly in Mexico15. Lucio’s phenomenon may present in either untreated leprosy patient or in already fully treated diffuse lepromatous leprosy patient years later even in the absence if bacillary load16.
PATHOPHYSIOLOGY AND IMMUNOLOGY TYPE 1 REACTIONS
It is an example of delayed type of 1 hypersensitivity reaction. It is attributed to the upgradation reaction, with the lesions progressing towards the tuberculoid pole, with a reduction in bacillary load. At this phase there is strong lymphocyte response with a strong skin test positivity to lepromin antigens1718. In episodes of reversal reaction, skin lesions and nerves have showed infiltration with IFN-γ and TNF-secreting CD4+ lymphocytes producing oedema and inflammation19 20. A significant elevation in the levels CXCL10 was found in those having a reaction when compared to those without a reaction2122. Increased FoxP3 staining was noted in reversal reaction patients compared with the non- reactional states and cases of ENL, suggesting a role of the regulatory T cells22.
TYPE II REACTIONS
Type II reaction occurs due to the deposition of immune complexes in the circulation23. The reactions show an increase in the levels of IL-1β, IFN-γ, TNF- α and other cytokines along with increase in levels of acute phase reactants like α-1 antitrypsin, C-reactive protein, amyloid24. Peripheral blood neutrophilia is so seen at the time of the reaction with neutrophils being the major contributors of TNF production, that produces tissue damage in leprosy. Microarray analysis have demonstrated that neutrophil recruitment in ENL involves the heightened expression of E-selectin and increased levels of IL-1β, leading to adhesion of neutrophils to the endothelial cells25.TNF-α may be responsible for the augmentation of the immune response so as to eliminate the pathogen and/or acts as a mediator, responsible for the pathologic manifestations of the disease. Either the cells or the lipoarabinomannan component of cell wall of M. Leprae can stimulate the production of TNF-α. Other than these, the protein-peptidoglycan complex, and muramyl dipeptide, mycolyl-arabinogalactan-peptidoglycan complex of Mycobacterium species, can all generate TNF-α release26.
TYPE III LEPRA REACTION
In Lucio’s phenomenon, the capillary endothelium is infected by the bacillus, leading to the proliferation of the endothelial cells, resulting in thrombosis and occlusion of vessels24. Laboratory investigations show increase in acute phase reactants such as α1-antitrypsin, C-reactive protein (CRP), α1-acit glycoprotein (AGP), and γ-globulins27.
PRECIPITATING FACTORS FOR LEPRA REACTION TYPE I REACTION
Risk factors include vaccination, MDT, pregnancy, puerperality, infections, stress, trauma, and oral contraceptive use. The number of skin lesions have been described as an individual risk factor28. Studies show that patients with the involvement of three or more body segments have ten times more chances of incurring neural damage and reversal reaction29. Facial involvement by the lesion also precludes the development of reversal reaction30. Recent studies show that there may be a genetic component involved12.
TYPE II REACTION
Risk factors include emotional and psychological stress, puberty, pregnancy, vaccination, infection1431.
CLINICAL MANIFESTATIONS TYPE I REACTION
They occur mostly within the first 6 months of starting multidrug therapy (MDT)32. Following treatment, the lesions which were regressing or turning into hypochromic macules suddenly become erythematous and oedematous, some of which may become scaly or in rare occasions ulcerate33. The existing lesions get inflamed but no new lesions appear. The lesions which were previously unnoticed or were invisible patches now become prominent which may give the false impression of the new lesions cropping up. The newly inflamed lesions are usually painless though tenderness can be elicited. Sometimes there may be a
burning sensation, pain in the face and extremities. Within the first 12 months of therapy, most of the patients experience isolated neuritis. Already existing peripheral neuropathy (sensory, motor, autonomic) and nerve thickening may become more prominent. The most commonly involved nerves in order of frequency being Ulnar, median, posterior tibial, fibular, radial, and facial nerves.
The patients may present facial palsy, foot drop and claw hand due to neural dysfunction. Palmar and plantar areas show hyperesthesia and widespread nerve damage28. Damage to the facial nerve results in lagophthalmos31. Neural damage is of importance as it stands to be the main reason behind the deformities in the due course of reversal reactions. Such episodes maybe painless as in silent neuritis. Sensory or motor dysfunction without the presence of skin lesions in type 1 and type 2 reactions is called as silent neuritis29. It may cause scleritis, iritis and in rare instances lead to blindness. When the reactions become severe the patient may present with features like fever, weakness, bone pain, lymphadenopathy, joint pain, and generalized oedema. Systemic symptoms are more in patient of lepromatous leprosy than borderline leprosy. Reversal reactions are not associated with fever and the patient’s clinical condition is usually good1331
Grading of Type I reaction34
1. Mild – Erythematous raised skin lesions with no evidence of neuritis.
2. Moderate - Erythematous patches/ plaques with effusion of joints
3. Severe – Ulceration of the skin lesions/ neuritis causing paralysis or impending paralysis
TYPE II LEPRA REACTION
These reactions can occur from anytime as in the early course of starting multi drug therapy or in late periods or even following the completion of the treatment as the immune response takes long period to eliminate the dead bacillus from the macrophages. In most of the cases, it occurs within three of initiation of the treatment. Lepromatous leprosy patients may detoriate suddenly and this is very rarely seen in the cases if BL leprosy. Multiple organs and systems can be involved.
Based on mode of onset of reaction35
1. Rheumatic type – Starts with fever, joint manifestations and skin lesions manifest later.
2. Exanthematous type – Starts with fever and skin lesions simultaneously.
3. Mixed type – Starts with fever, skin lesions and joint manifestations simultaneously.
Grading of Type II reaction
1. Mild – Temperature up to 100◦ F and a few skin lesions on one or more extremities.
2. Moderate – Temperature up to 102◦F. Skin lesions are more numerous in all four limbs and few on the trunk and face with occasional vesicles and pustules. Extracutaneous signs present.
3. Severe – Temperature above 102◦F. Vesiculation and pustulation present.
Visceral involvement present.
CUTANEOUS MANIFESTATIONS
Erythema nodosum leprosum (ENL) is the most commonly seen cutaneous feature of type II reaction. It was first described by Green (1929) to be an “acute exanthem of leprosy”. The lesions present as tiny 2.5mm nodules and sometimes as papules which are typically warm, tender and painful. They may be either be superficial lesions that appear to be elevated from the surrounding skin or may be deeper and such lesions are better appreciable when they are palpated. The lesions appear dome shaped with an erythematous to ducky brown ill-defined margins. They appear in crops that blanch when slight finger pressure is applied and soon become evanescent lasting for only 2-3 days and very rarely are present for longer duration. If multiple lesions are present, then have a bilateral and symmetrical distribution. More lesions are seen to crop between 5.00 to 6.00PM and this is attributed to the diurnal variation of endogenous cortisol with the production being at its lowest during the aforementioned time.
ENL can occur in any region of the body that has a lepromatous infiltrate and is seen as bilaterally symmetrical lesions. ENL lesions are more in trunk and other sites include flexor aspect of forearms, face, arms, medical aspect of thighs. They may occur on skin in any portion of the body except for the areas which are considerably warmer including axillae, groin, scalp, perineum and the intertriginous areas as M. leprae proliferates preferably in the relatively cooler
areas. Occasionally lesions of the palms and scalp can be noted. As the lesions desquamate and start subsiding, they tend to leave behind a bluish tinge in the skin. In instances of incomplete recovery, chronic painful panniculitis supersedes which may persist for years.
When larger areas of skin and subcutaneous tissue become involved, they become fixed to the underlying fascia, muscle or bone and leading to immobilisation in joints and deformities. The involved tissue lacking a proper vascular supply, ulcerates even with minima pressure or trauma. The consequently formed ulcer heals taking a prolonged period of time.
Type II reaction can also present as bullae, vesicles, pustules, ulcerated or like lesions of erythema multiforme36. Cases of bullous type of ENL have been reported from South America, Mexico, India with one case being reported from Nepal37. In bullous type of ENL, the histopathology sections show an intra epidermal cleft along with diffuse neutrophilic infiltrates and a few foamy histiocytes and a few rod shaped lepra bacilli. 37 Occasional cases of Erythema necroticum ulcerans has been seen in adults, but not in paediatric population one single exception of a case reported by Pandhi et al6. Haemorrhagic and pustular variants of ENL carry a poor prognosis35. When lesions recur, they tend to occur at the same site as the previous ones. Pretibial ulceration can also be seen in ENL due to dysproteinaemia).
Conflicting reports have been arising probing into the relationship between leprosy and HIV for a long period of time. By the virtue of studies carried out, increased prevalence of active tuberculosis and other mycobacterial
infections amongst the HIV, was expected, particularly in the lepromatous spectrum. It could be possibly due to the prevalence of ENL in areas where HIV and leprosy are endemic. Earlier literature is complete with cases of Type I reactions (reversal reactions) occurring more frequently amongst the HIV infected. Severe neuritis, poor prognostic outcome and increase in number of relapses are common among the HIV infected leprosy patients38. Gebre et al39 recorded showed that the HIV infected had a higher risk of developing ENL reactions. Nand Lal Sharma et al38also reports similar findings. HIV being a neurotrophic virus may produce necrotizing vasculitis of the nerves40. Since both M.leprae and HIV are neurotrophic, their coinfection results in neuropathy that is described as steroid resistant41. Vreeburg et al42 also noted that although neuritis of lepra reactions occurs at an equal frequency in both the HIV infected as well as non-infected buts equally common in both HIV positive and HIV negative patients. Recent studies have also proved that HIV co infection has no significant effect on epidemiology, clinical, immunological and histological spectrum of leprosy. The exact mechanisms of ENL behind the cases of co infection in patients is yet to be fully elucidated.
NEURITIS
Type II reaction causes neural inflammation. In severe reactions, nerves may become painful with rapid loss of function. But neuritis is not as pronounced as in Type I Lepra reaction. Affected nerves besides being tender are mildly enlarged due to inflammation.
CONSTITUTIONAL SYMPTOMS
Systemic manifestations are seen in type 2 lepra reactions and include fever which usually is more noticeable during the evenings, is of high grade and is associated with chills and rigors. There is exhaustion and prostration by pain, myalgia, headache, anorexia, insomnia and depression. Oedema of the hands, feet and face, painful dactylitis are some other manifestations of Type II reaction.
OCULAR MANIFESTATIONS
Eye maybe involved in ENL and includes keratitis, scleritis, conjunctivitis, lagophthalmos, episcleritis, iridocyclitis and secondary glaucoma. Among these iridocyclitis stands to be the most dreaded complication leading to irreversible blindness in leprosy. Symptoms include redness, decreased vision, photophobia, epiphora and pain in the eye radiating to the brow and the temple. The eyelids appear swollen in severe reactions due to ocular inflammation and congestion.
The eye is diffuse involved with erythema with it being the most intense at the limbus 360◦ around the cornea (ciliary flush) with severe ocular tenderness. Loss of lustre of cornea is seen lustre of the cornea due to corneal oedema, presence of proteins and inflammatory infiltrates in the aqueous chamber (flare and cells). The affected pupil shows mild constriction when compared with the other normal eye. The above-mentioned symptoms are present in varying degrees, depending upon the nature of the reaction and its
severity. This should be quickly diagnosed and treated as delay in treatment may lead to permanent loss of vision.
Studies done till date show that orbital involvement by reaction has been reported only in one case of lepra reaction43. Vasculitis due to due to Wegener’s granulomatosis and arteritis have been implicated as the reasons behind orbital apex syndrome, but only in one case studied up to date, it has been attributed to ENL. Lepromatous process also involve the sinuses. Dhaliwal et al43, described the involvement of ethmoidal sinus, left maxillary along with destruction of medial orbital wall, which causes the lesions to spread to the orbit. Orbital apex involvement leads to damage to the nerves coming out through it including III, IV, V and VI cranial nerves, producing complete ophthalmoplegia, loss of visual acuity and decreased sensations in the eye. Ophthalmic, posterior ciliary or central retinal artery may get involved by inflammation of lepra reaction causing sudden blindness. Proptosis may occur due to the oedema and inflammation of the connective tissues surrounding the eye. Loss of vision and proptosis are medical emergencies and require immediate diagnosis and treatment.
ENT MANIFESTATIONS
Nasal mucosa, buccal mucosa, palate, tongue can be involved in Erythema nodosum Inflammation in these areas results in rhinitis, nasal blockade with difficulty in breathing, erosion, epistaxis, ulceration and in occasion perforation of the septum of nose. Soft palate involvement leads to ulceration of uvula and destruction, healing of which leading to scarring and deformity of the fauces. Such erosions and ulceration can also been seen in the hard palate44.
Laryngeal involvement in lepra reaction causes cough, hoarseness of voice, aphonia, raucous voice and sometimes there maybe respiratory compromise35. In the oral cavity gums may also be involved with diffuse swelling of the gums.
MUSCULOSKELETAL MANIFESTATIONS
Myositis occurs as a manifestation of type II reaction. The chief muscles of involvement being vasti and brachioradialis. The muscles become woody hard. Painful and tender nodules are formed along the muscle fibres rendering the movements difficult. Periostitis occurs as a part of lepra reaction and can affect lower end of fibula, tibia, phalanges, upper end of ulna, and calcaneum. In the tibia, it clinically seen as tender swelling and thickening along the anterior curvature. X ray features include the features include thickening of the cortex with periosteal elevation, and increased anterior curvature. The digits are inflamed producing dactylitis.
Osteoporosis occurring as a chronic complication of Type II reaction chiefly affects mainly the long bones, ribs, phalanges and metacarpals. X ray shows areas of rarefaction and pseudocyst formation. All these changes produce weakening of bones with resultant pathological fractures. Subarticular collapse of bones resulting in of shortening of digits may occur. “Double stripe sign” in bone scan is visualised in distal tibiae45. It can also be appreciated in hypertrophic osteoarthropathy. The joint manifestations of Type II reaction include arthralgia and arthritis producing non paralytic deformation of joints. It has been found that the joint manifestations are inversely proportional to that of the skin lesions35.
When joint is involved one can notice soft tissue swelling, sub articular collapse, osteoporosis, ankylosis in X rays.
LYMPH NODE ENLARGEMENT
Tender lymphadenopathy is seen in 50% of cases with ENL. One study has reported pre auricular lymph node enlargement to have a predictive role in lepra reaction35. Lymph node enlargement can also be seen in the inguinal, intercostal, axillary and cervical nodes. The initially tender nodes during the course of time become non tender and matted. In very rare instances, the overlying skin maybe necrosed with discharging sinus46.
CARDIOVASCULAR MANIFESTATIONS
Mild decrease in the blood pressure is noted in lepra reaction. The blood vessels show evidence of vasculitis. Friction rub of pericardium has also been reported.
RESPIRATORY SYSTEM MANIFESTATION Pleuritis occurs with Type II reaction.
CHANGES IN TESTIS AND EPIDIDYMIS
Epididymis and testis may become acutely inflamed in lepra reaction and is one of the most important clinical manifestations in males. One or both the testis may become tender resulting in diffuse enlargement. One may develop testicular atrophy rapidly following an acute episode of orchitis or over a long period of time gradually following low grade orchitis. With testicular atrophy
and loss of production of testosterone, and production of oestrogen, gynaecomastia manifests.
CHANGES IN BREAST
The breast becomes tender and inflamed with a picture like that of acute mastitis.
CHANGES IN ABDOMINAL VISCERA
Tender hepatic enlargement, with the liver extending below the costal margin maybe noted. Recurrent bouts of lepra reaction may result in persistent hepatomegaly with ascites, amyloidosis of liver and splenomegaly. Renal involvement may show up as haematuria and very rarely as oliguria. Recurrent lepra reaction with chronic inflammation may also cause amyloid deposition in the renal parenchyma. Adrenal inflammation and decreased functional capacity of adrenals with peritonitis can also occur.
TYPE III LEPRA REACTION
This may be seen during anytime, from 1–3 years after the onset of disease and is more frequently seen in patients who have not been treated or those who have been inadequately treated. Cutaneous manifestations include painful erythematous lesions which progressing to irregular and angulated ulcers with , necrotic and jagged-edges, predominantly in the extremities 47. Signs of neural involvement and constitutional symptoms are rare.
HISTOPATHOLOGY OF THE REACTIONS TYPE 1 REACTION
In type 1 reaction oedema is seen in the upper dermis along with vaguely formed granulomas. Epidermal erosion, spongiosis, inflammatory infiltrate composed of foreign body giant cells, Langhan’s giant cells is accompanied by fibroblastic response in the dermis. In severe reaction, ulcer, necrosis and inflammatory infiltration by neutrophils may be seen48. Inflammatory cells are seen infiltrating the epidermis and along with increased neural destruction.
Oedema is present both inside and around the granulomas producing destruction the adjacent nerves28.
TYPE 2 LEPRA REACTION
Two histopathological variants of ENL have been described. First variant was reported by Ridley and is called “the pink nodule type” or classical ENL (or mild ENL form). Clusters of neutrophils are seen around the small granulomas. Mast cells, Eosinophils, plasma cells are also present. Classical characteristics of vasculitis affecting small or medium sized vessels include necrotising lesions and thrombosis which have been reported in around 25% of the cases. Vasculitis appears to be the easiest change appreciated in these lesions and involves infiltration by neutrophils, haemorrhage, and formation of thrombus, and it may be severe in ENL with necrosis. Such necrosis is more often seen in epidermis and dermis with associated collagen degeneration can be observed all leading to dermal fibrosis48. Lesions of untreated patients show acid
resistant bacilli (ARB), whereas in those receiving therapy granular and fragmented ARB are often found.
LUCIO PHENOMENON
Lucio phenomenon shows the following histopathological features a) Endothelial cell colonisation by lepra bacilli
b) Proliferation of endothelial cells, with thickening of the vessel wall with eventual obliteration of vessel
c) Hypoxia mediated angiogenesis d) Ectasia of vascular channels and
e) Thrombosis. Diffuse lepromatous leprosy is characterised by necrotising lesions and displays two histopathological patterns: with one of them being non inflammatory and other being inflammatory with neutrophilic infiltrates and panniculitis. The first pattern is produced due to the endothelial cell colonisation by Mycobacterium leprae. The second pattern is a combination of pre-existing occlusive vasculopathy, occurring along with lepra reaction at present and is considered as a variant of ENL.
DIAGNOSIS OF REACTIONS
TYPE 1 REACTION: Mainly depends on the clinical features.
REVERSAL REACTION
DOWN GRADING REACTION Occurs in In near-lepromatous
and borderline patients
In near-tuberculoid and borderline patients
Nature of Lesions
a) No new lesions / only few new lesions b) Pre-existing lesions become more
pronounced c) Sensory deficit does not progress d) Previously involved nerves become more
inflamed but now new nerves are involved
a) Increase in the number of new skin lesions
b) Pre-existing lesions become less pronounced c) Sensory deficit progresses to involve new areas
d) New nerve involvement seen
Bacteriological index
Decreases Increases
Lepromin test Negative tests revert to positive
Positive reverts to negative or there is weak positivity Histopathological
picture
Oedema in and around granuloma, infiltration by neutrophils and mononuclear cells.
Granulomas with extracellular oedema
TYPE 2 REACTION B. HEMATOLOGICAL
1) Anaemia - Normocytic normochromic anaemia, megaloblastic anaemia (Attributed to sulpha drugs interfering with folic acid metabolism), aplastic anaemia (due to toxins and drugs interfering with the bone marrow) and haemolytic anaemia (more in G-6P- D deficient individuals) can occur.
2) Reticulocytosis - In the event of severe reactions with haemolytic episodes, abrupt decrease in haemoglobin values with increase in the reticulocyte count. Haemolysis is reflected in increased reticulocyte count which may go up to 2%.
3) Leucocytosis is attributed to the immune complexes’ deposits, inflammatory process.
4) Thrombocytosis as a reactive change to anaemia in ENL.
5) Elevation of ESR due to the inflammatory process.
C. BIOCHEMICAL FINDINGS
Abnormalities of liver function tests in T2R have been reported. It mainly includes a deficiency in coagulation factors and rise in alanine aminotransferase.
With moderate hepatic dysfunction, these levels completely come back to normal when the reaction subsides. In severe reaction with haemolytic crises, a very mild rise in the levels of serum bilirubin (1-2mg%) has been observed.
Changes in the albumin globulin ratio have also been reported, mainly brought about by the increase in α – globulin49.
D. URINE EXAMINATION
Patients with type II reaction also have evidence of renal involvement as reflected by albuminuria, (traces to 1 +), pus cells and epithelial cells, numerous erythrocytes, and presence of granular casts in urine. Bile pigments can be found I the T2R during the acute phase. Haemoglobinuria can be found in some with T2R and can present with smoky urine. Amyloidosis has to be rue out in any patient with T2R with chronic persistent proteinuria.
E. SKIN BIOPSY AND HISTOPATHOLOGY TYPE I LEPRA REACTION
Histopathological observations in type 1 reactions include lymphocyte accumulation within granuloma, oedema in granuloma and papillary dermis followed by folliculotropism and lymphocytic panniculitis.
TYPE II LEPRA REACTION
Histopathological observations in type 2 reaction include the presence of neutrophils in the granuloma, leukocytoclasia, papillary dermal oedema, lobular and septal neutrophilic panniculitis50
F. FLUORESCENT MICROSCOPY
Deposits of IgG and C3 complexes can be found in the early phases of EN.
TYPE III LEPRA REACTION
The routine laboratory findings include leucocytosis mostly due to absolute neutrophilia, high ESR, anaemia, hypergammaglobulinemia and positive cardiolipin antigen tests for syphilis. The diagnosis can be confirmed with immunofluorescence and histopathological examination.
DIFFERENTIAL DIAGNOSIS TYPE 1 REACTION
Cutaneous disease simulants 1. Urticaria
2. Angioedema 3. Erysipelas 4. Gyrate erythema
5. Well’s syndrome (eosinophilic cellulitis) 6. Erythema multiforme
7. Subacute and acute lupus erythematosus 8. Drug eruptions (including fixed drug eruption) TYPE II REACTION
Cutaneous disease simulants
1. Acute cutaneous lupus erythematosus
2. Neutrophilic dermatoses (sweet’s disease and pyoderma gangrenosum)
3. Subcorneal pustular dermatosis (Sneddon-Wilkinson Disease) 4. Pityriasis lichenoides et varioliformis (PLEVA)
5. Varicella or disseminated herpes zoster Simulants of septal panniculitis of ENL
1. Erythema nodosum 2. Erythema induratum
3. Alpha-1 antitrypsin deficiency
4. Pancreatic disease and pancreatic carcinoma
5. Vasculitides - cutaneous polyarteritis, lupus profundus
6. Typical and atypical mycobacterial infections, calcific arteriopathy (calciphylaxis)
7. Cholesterol embolus
8. Lymphoproliferative disorders (lymphomatoid granulomatosis, B-cell lymphoma, and cutaneous T-cell lymphomas
TYPE III REACTION
1. Leukocytoclastic vasculitis
2. Vasculopathy associated with cryoglobulinemia 3. Macroglobulinemia
4. Calciphylaxis
5. Cholesterol embolism 6. Coumadin necrosis 7. Factitial dermatitis51
MANAGEMENT OF REACTIONS
GENERAL PRINCIPLES OF MANAGEMENT 1. Continuation of Anti leprosy drugs 2. Counselling to relieve stress
3. Treatment for inter-current infections and infestations 4. Analgesic, anti-inflammatory drugs (NSAIDS)
5. Anxiolytics (at bedtime)52 TYPE 1 REACTION
1. If the reaction is mild with no evidence of neuritis (pain, loss of sensation or function) - Analgesics, such as acetylsalicylic acid or paracetamol.
2. If the reaction is severe with evidence of neuritis - Analgesics and corticosteroids, such as oral prednisolone. It is started with 40 - 60 mg daily (up to a maximum of 1 mg/kg) with the reaction subsiding within few days of treatment. The dose is then decreased step by step, weekly or fortnightly and then is eventually stopped. In most of the cases, the reactions and neuritis can be successfully treated with a standard 12-week course of prednisolone but some researchers advocate the use of steroids for long periods of time.
TYPE 2 REACTION
1. In mild reactions - Analgesics, such as acetylsalicylic acid or paracetamol, and corticosteroids, such as oral prednisolone.
2. In severe type 2 reactions, not responsive to corticosteroids or in whom corticosteroids are contraindicated – Higher doses of clofazimine or thalidomide maybe used under strict medical supervision.
ANTI REACTION DRUGS 1.CORTICOSTERIODS In type 1 lepra reaction
Mechanism of action: Their main effects are to inhibition of cellular immune response and suppression of inflammatory response against M. leprae antigens in the skin. Corticosteroids increases vasodilation by inhibiting the release of mediators such as arachidonic acid (prostaglandins) metabolites and platelet activating factor (PAF), vasoactive amines, neuropeptides, interleukin-1 (IL-1), TNF-α, and nitric oxide (NO). They inhibit adhesion of neutrophils, eosinophils, and lymphocytes to the endothelial cells, their migration to the inflammation site, and decrease vascular permeability. They also inhibit phagocytosis and free radical production.
Dosage: Started at a dose of 40 mg for cases of type 1 reactions. However in those with neuritis, it is started at a dose of 1 mg/kg (60 mg) and may go up to 2 mg/kg depending on the severity of the reaction.53. Prednisolone is usually tapered over a period of time with clinical signs of recovery to 20 mg/day.
Pulse therapy with intravenous methylprednisolone has also ben advocated to control reactions. It is indicated in severe cases of reversal reactions, in old cases who have received oral corticosteroids for prolonged
periods for either acute or chronic neuritis. The recommended period of therapy is 6–9 months in patients with borderline (BB) leprosy, 4–9 months in patients with borderline tuberculoid (BT) leprosy, 6–18 months in patients with borderline lepromatous (BL) leprosy. However, depending on the severity, the duration of the treatment may last up to 2years or longer.
Patients with new onset neural lesions, lesions with a duration of less than 6months respond well to treatment than those in whom treatment has been initiated in the later stages.
The treatment with corticosteroids must be tailored according to the patient’s needs and must be started at the right dose and tapered gradually depending upon the status of sensory and motor functions during the follow up period.28
In type 2 lepra reaction
Mechanism of action: Acts by suppressing the inflammation.
Intermittent usage or corticosteroids along with pulse therapy and rapid tapering within 2 – 3 weeks has been suggested for the treatment of type 2 reaction. Side effects: Long term therapy with corticosteroids is to be avoided due to the steroid dependence and steroid related side effects.
2. THALIDOMIDE
Mechanism of action – Inhibits the release of TNF-α.
Dosage: It is started a t dose of 100–300 mg/day in recurrent cases and provides prolonged remission14. It is the drug of choice for maintenance therapy
in type II lepra reaction. Thalidomide has been shown to be superior to pentoxifylline and acetyl salicylic acid with rapid control of ENL.
Side effects: 20- 30% of cases develop neuropathy that is often masked by neuropathy caused by leprosy itself.54. Thalidomide is teratogenic drug and is contraindicated in early stages of pregnancy45. Alternatives during pregnancy include Revlimid and aktimid.
3.CLOFAZAMINE
Mechanism of action- Being strong lipophilic drug, it binds to the mycobacterial DNA55. The antibacterial activity of clofazimine is mediated by the accumulation of lysophospholipids 56.
Clofazimine takes 4-6 weeks to produce a significant clinical response, and henceforth never used as the sole drug in the treatment of severe type 2 reactions. But clofazimine has proved to be efficacious in patients while withdrawing from corticosteroids on in patient show have dependent on corticosteroids.
Dosage: Clofazimine is given at dose of 300mg daily, which is split into doses of 100mg each. Clofazimine is never advocated for a period greater than 12 months.57
4. CHLOROQUINE
Mechanism of action: Used on account of their anti-inflammatory action.
These include inhibition of prostaglandin synthetase, reduced PG synthesis and
decreased inflammatory damage, lysosomal membrane stabilization58. Other mechanisms include suppression of complement activation, platelet aggregation, and enhanced fibrinolytic activity59. Drug is easily, easily available and has been proven efficacious in mild episodes of both borderline leprosy and E.N.L.
Side effects: Minor side effects include visual problems, gastrointestinal disturbances and skin rashes. It is contraindicated in pregnancy.
5.ANTIMONIALS.
Mechanism of action – Currently not fully studied.
The use of these drugs is restricted on account of parenteral route of administration
Mild and moderate E.N.L cases have responded to both tri and pentavalent compounds of antimony and have been found be useful in relieving bone and joint problems. Of late, pentavalent antimonials (such as sodium antimony gluconate) have proven to be more effective and less toxic when compared to the trivalent antimony compounds.
Side effects: Severe side effects include anaemia, cardiac damage and nephropathy.
6.COLCICHINE
Mechanism of action – Experiments have proved that it suppresses Arthus reaction in rabbits even with the deposition of immune complexes60. This is due to the suppression of neutrophil chemotaxis. Various studies have proved that in
addition to immuno-regulatory action, the drug is capable of restoring T cell 48 balance, which occurs with the onset of E.N.L. Beneficial effects on nerve pain and joints have also been reported with its usage.49.
MATERIALS AND METHODS
STUDY PLACE: Conducted in the Pathology Department of Chengalpattu Medical College and Hospital, Chengalpattu in collaboration with Central Leprosy Teaching and Research Institute, Chengalpattu.
STUDY DESIGN: The present study is a prospective study conducted in the Department of Pathology and Central Leprosy Teaching and Research Institute, Chengalpattu during the period of July 2018- September 2019.
Ethical clearance for the study was obtained from the Institutional Ethics Committee of Chengalpattu Medical College, Chengalpattu and Central Leprosy Teaching and Research Institute, Chengalpattu.
STUDY POPULATION: A total sample of 50 cases of lepra reaction were analyzed from July 2018- September 2019.
INCLUSION CRITERIA:
• All cases of lepra reaction EXCLUSION CRITERIA:
• Indeterminate Hansen’s
• Neural leprosy
• A total of 50 cases of lepra reaction will be randomly selected from the outpatient department and wards of the Central Leprosy Teaching and Research Institute, Chengalpattu.
• 2ml of venous blood is withdrawn from the patient with lepra reaction
Complete blood count using automated analysers measuring WBC count, RBC count, Hb, PCV, MCV, MCH, MCHC, DC, RDW
• Peripheral smear stained using Leishman staining
• Reticulocyte count done using New Methylene blue PROCEDURE FOR COMPLETE HEMOGRAM:
Sample is fed in an automated 3-part analyser running on the Coulter’s principle which gives the values mentioned in the study.
PROCEDURE FOR LEISHMAN STAINING:
1. Smears are air dried.
2. Smear covered with 8 drops of Leishman stain for 2 minutes.
3. After 2 minutes, twice the volume of buffered water is added and left for 10 minutes. A scum of metallic sheen forms on the surface.
4. The stain is washed away using tap water.
5. The back of the slide is wiped clean, set it upright in the draining rack and allowed to dry.
6. After drying is mounted on the microscope and examined.
PROCEDURE FOR RETICULOCYTE COUNTING
1. 2-3drops of filtered new methylene blue solution is taken in a 12 × 75 mm test tube.
2. Double the amount of blood is added to it and mixed well.
3. The mixture is kept in an incubator at 37°C for 15 minutes.
4. The sample is then taken out, after gentle mixing, a small drop from the mixture is placed on a glass slide, a thin smear is made and allowed to air dry.
5. The smear is examined under the microscope using oil-immersion objective. Mature red cells stain pale green-blue. Reticulocytes show deep blue precipitates of fine granules and filaments in the form of a network (reticulum) Most immature reticulocytes show a large amount of precipitated material in the form of a mass, while the most mature reticulocytes show only a few granules or strands. Any nonnucleated red cell is considered as a reticulocyte if it contains 2 or more blue-stained particles of ribosomal RNA.
6. 1000 red cells are counted and the number of red cells that are reticulocytes are counted and reticulocyte percentage is calculated using the formula
Reticulocyte percentage – Number of reticulocytes counted ÷ Number of RBC’S counted
STATISTICAL ANALYSIS
The primary data was entered in MS Excel and analyzed using SPSS 20v.
The results were presented in terms of tables and graphs. The descriptive statistics frequency and percentages were calculated.
The association between the categorical variables were analyzed by unpaired t test.
TYPE I REACTION
TABLE 1: Various haematological parameters in lepra reaction type I
TYPE II REACTION
TABLE 2: Various haematological parameters in lepra reaction type II PATIENT AGE SEX TYPE OF REACTION RBC COUNT WBC COUNT Hb PCV MCV MCH MCHC Platelet count Neutrophil Lymphocyte Mixed RDW Retic
mllions/cu mm milions/cu mm gm/dl % pg fl % lakhs % % % % %
1 28 M TYPE II 2.8 4700 2.9 21 73 23 30 1.6 63 6 1 13.4 0.3
2 26 M TYPE II 2.9 7200 7.6 25 73 26 30 2.3 74 10 3 13.6 0.3
3 22 M TYPE II 3.1 8100 8.4 25 79 26 32 2.5 75 13 4 14 0.4
4 69 M TYPE II 3.2 9600 9.4 26 85 27 33 3.1 75 16 6 14.5 0.8
5 35 M TYPE II 3.2 16400 9.4 28 86 29 34 3.3 77 18 7 15.1 1
6 70 F TYPE II 3.3 17700 9.8 29 89 29 34 3.8 78 23 7 15.8 1
7 60 F TYPE II 3.9 19500 11.6 36 90 30 34 4.4 84 24 8 16.2 1.2
8 75 M TYPE II 5 21400 13.5 40 94 31 36 5.3 90 29 9 18.1 1.2
AVERAGE 48.125 3.425 13075 9.075 28.75 83.63 27.63 32.88 3.2875 77 17.375 5.625 15.088 0.775 STD DV 22.44636 0.716638981 6375.343128 3.1043 6.274 7.855 2.615 2.1 1.196945517 7.85584405 7.707834604 2.7223 1.083 0.388219
TABLE 3: p value estimation, (S)- Significant (<0.005)
TYPE I REACTION AVG STD DV
TYPE 2 REACTION AVG STD DV
T P
value
RBC count 4.18 0.72 3.45 0.71 2.74 <0.05 WBC count 9390.47 2590.22 13075 6375.34 1.60 >0.05
Hb 11.70 2.61 9.07 3.10 -2.25 <0.05
PCV 33.76 6.06 28.75 6.27 -2.08 <0.05
MCV 70.33 22.20 83.63 41.5 0.88 >0.05
MCH 28.21 3.37 41.5 25.17 1.49 >0.05
MCHC 34.26 3.35 32.88 2.1 -1.5 >0.05 PLATELET
count
2.96 1.12 3.28 1.19 0.70 >0.05
NEUTROPHILS 61.47 11.89 77 7.85 -4.66 <0.001(S) LYMPHOCYTES 31.11 12.04 17.37 7.70 -4.16 <0.001(S) MIXED 7.59 3.71 5.62 2.72 -1.76 <0.001(S)
RDW 13.98 1.95 15.08 1.57 1.74 >0.05
RETIC count 0.89 0.50 0.77 0.38 -0.77 >0.05
OBSERVATION AND RESULTS
A total number of fifty patients of lepra reaction were included in our study. There were 42 patients with Type I reaction and 8 cases with type 2 reaction.
AGE
TABLE 4: Distribution of reaction cases among different age groups
AGE GROUP
TOTAL NUMBER OF
CASES
TYPE I REACTION
TYPE II REACTION
<10 -
11-20 2 (4%)
21-30 6 (12%) 3 3
31-40 4 (8%) 3 1
41-50 5 (10%) 5
51-60 16 (32%) 15 1
61-70 13 (26%) 11 2
71-80 4 (8%) 3 1
AVERAGE 46.57 5.71 7.1
CHART 1: Distribution of reaction cases among different age groups The mean ages of patients with Type I and Type II reactions were 52.97 years and 48.12 years, respectively. 16(32%) of the patients contributed to the majority of the reactions were found to be in the age group of 51- 60 years. The next major contribution belonged to the age group of 61-70 years which included 13(26%) of cases. The lowest number of reaction cases were reported in the age group of 11- 20 years which included only two (4%) cases (TABLE 4).
<10 4% 21-30
13%
31-40 9%
41-50 11%
32%
26%
AGE GROUP
<10 21-30 31-40 41-50 51-60 61-70 71-80
SEX
TABLE 5: Distribution of reaction cases among different sexes
MALES FEMALES
TYPE I REACTION 18(75%) 24(92.30%) TYPE II REACTION 6(25%) 2(7.69%)
Chart 2: Distribution of reaction cases among different sexes
There was a total of 24 male patients and 26 female patients, with a sex ratio of 12.13. The sex ratios of patients with Type I and Type II reactions were 1.3 and 3:1 respectively. Thus, female patients constituted 57% of the total number of cases (TABLE 5)
43%
57%
SEX
Males Females
INCIDENCE OF DIFFERENT TYPES OF LEPRA REACTION ALONG THE SPECTRUM OF LEPROSY
TABLE 6: Incidence of different types of lepra reaction occurring along the spectrum of leprosy
TYPE OF LEPROSY
TYPE I REACTION UPGRADING
TYPE I REACTION DOWNGRADING
TYPE II REACTION
BT 30 (88.24%) -
BB 2 (5.88%) 4 (50%) -
BL 2 (5.88%) 4 (50%) 2 (25%)
LL - - 6 (75%)
HISTIOD - - -
CHART 3: Incidence of different types of lepra reaction occurring along the spectrum of leprosy
Out of the 42 patients with Type I reaction, 34 were upgrading and 8 were downgrading (TABLE 6). It was also noted that out of 34 patients in Type I upgrading reaction, 30 (88.24%) were primarily diagnosed as borderline tuberculoid Hansen’s disease, 2 each (5.88%) were diagnosed as mid borderline and borderline lepromatous Hansen’s disease. Among the 8 patients with downgrading reaction, 2 (25%) were diagnosed with borderline tuberculoid downgrading to borderline lepromatous leprosy. 6 (75%) patients with mid borderline were downgrading to lepromatous leprosy. (CHART 3)
TYPE I UR, 0TYPE I RR, 0 TYPE II , 75%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
100.00%
BT BB BL LL
INCIDENCE OF LEPRA REACTIONS
INCIDENCE OF LEPRA REACTION
ONSET OF REACTION
TABLE 7: Onset of reaction in relationship to MDT ONSET OF
REACTION IN RELATION TO MDT
TYPE I REACTION TYPE 2 REACTION
Started with reaction 3 (7.15%) 1 (12.5%)
< 6months 5 (11.90%) -
6months – 1 year 6 (14.28%) -
1 – 3 years 7 (16.68%) 4 (50%)
3 – 5 years 16 (38.11%) 2 (25%)
>5years 5 (11.90%) 1 (12.5%)
CHART 4: Onset of reaction in relationship to MDT
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
STARTED WITH REACTION
<6MONTHS 6MONTHS‐
1YEAR
1‐3YEARS 3‐5YEARS >5YEARS
INCIDECE OF REACTIONS
ONSET OF REACTION IN RELATION TO MDT
ONSET OF REACTION
Type I Reaction Type II Reaction
It was observed that among the 42 patients with Type I reaction, 3 (7.15%) presented with reaction before initiation of MB MDT (Multibacillary Multidrug therapy). 5 (11.90%) developed Type I reaction within 6 months of starting MBMDT and 6 (14.28%) developed the reaction after 6 months. 7 (16.68%) developed Type I reaction between 1-3 years after initiation of therapy and 16 (38.11%) developed the reaction between 3-5 years after starting therapy. 5 (11.90%) developed the reaction after 5 years of therapy.
Among 8 patients with Type II reaction, 1 (12.5%) presented with reaction before diagnosis and initiation of MB MDT and 4 (20%), 4 (50%) presented with reaction between 1-3 years, 2 (25%) within 3 -5 years after initiation of therapy. Only 1 (12.5%) developed Type II reaction 5 years after initiation of therapy. (TABLE 7)
RBC COUNT
CHART 5: RBC counts in different cases of lepra reaction
6 6
35
1
0 1
0 5 10 15 20 25 30 35 40
Type I Reaction Type II Reaction
NUMBER OF CASES
RBC COUNT
<3.5million 3.5-5.5million >5.5million
Among the 42 type I reaction cases 6 cases showed counts less than 3.5 million/cu mm, 35 cases showed counts between 3.5-5.5millions/cu mm.
Among the 8 type II reaction cases 6 cases showed counts less than 3.5 million/cu mm, 2 cases showed counts between 3.5-5.5millions/cu mm.
WBC COUNT
CHART 6: WBC counts in different cases of lepra reaction
Among the 42 type I reaction cases no case showed counts less than 4000cells/cu mm, 32 cases showed counts between 4000-11000cells/cu mm.
Among the 8 type II reaction cases no case showed counts less than 4000cells/cu mm, 4 cases showed counts between 4000-11000cells/cu mm, 4 cases showed counts greater than 11000cells/cu mm.
0 5 10 15 20 25 30 35
TYPE I REACTION TYPE II REACTION
WBC COUNT
WBC COUNT
HEMOGLOBIN
CHART 7: Haemoglobin levels in different cases of lepra reaction Among the 42 type I reaction cases, 19 cases showed haemoglobin levels less than 12gm/dl, 19 cases showed haemoglobin levels between 12-15gm/d and 4 cases showed haemoglobin levels greater than 15gm/dl.
Among the 8 type II reaction cases 7 cases showed haemoglobin levels less than 12gm/dl, 1 case showed haemoglobin levels between 12-15gm/d and no cases were found to have haemoglobin levels greater than 15gm/dl.
19
7 19
1 4
TYPE I REACTION TYPE II REACTION
NUMBER OF CASES
HEMOGLOBIN
>12gm 12‐15gm >15gm
PACKED CELL VOLUME
CHART 8: Packed cell volume in different cases of lepra reaction
Among the 42 type I reaction cases, 28 cases showed packed cell volume less than 37% and 14 cases showed packed cell volume greater than 45%.
Among the 8 type II reaction cases, 7 cases showed packed cell volume less than 37%, 1 case showed packed cell volume between 37- 45% and no cases showed packed cell volume greater than 45%.
28
7
0 1
14
TYPE I REACTION TYPE II REACTION
NUMBER OF CASES
PCV
<37 37‐45 >45
MEAN CORPUSCULAR VOLUME
CHART 9: Mean Corpuscular Volume in different cases of lepra reaction Among the 42 type I reaction cases, 18 cases showed mean corpuscular volume less than 80fl, 23 cases showed mean corpuscular volume between 80-100fl and 1 case showed mean corpuscular volume greater than 100fl.
Among the 8 type II reaction cases, 3 cases showed mean corpuscular volume less than 80fl, 5 cases showed mean corpuscular volume between 80-100fl and no case showed mean corpuscular volume greater than 100fl.
18
3 23
1 5
YPE I REACTION TYPE II REACTION
NUMBER OF CASES
MCV
>80fl 80‐100fl >100fl
