Case Reports

Diagnosis and Treatment of Leprosy Type 1 (Reversal) Reaction

Cutis. 2015 April;95(4):222-226

References

1. Kalisiak M, Yeung R, Dytoc M. Dermacase: leprosy. Can Fam Physician. 2009;55:55-56.

2. Kustner EC, Cruz MP, Dansis CP, et al. Lepromatous leprosy: a review and case report. Med Oral Patol Cir Bucal. 2006;11:474-479.

3. Nunez-Gussman J, Hwang L, Hsu S. Targetoid erythematous plaques: an unusual morphological presentation of multibacillary Hansen’s disease. Eur J Dermatol. 2001;11:65-67.

4. Scollard DM, Adams LB, Gillis TP, et al. The continuing challenges of leprosy. Clin Microbiol Rev. 2006;19:338-381.

5. Gelber RH. Leprosy (Hansen’s disease). In: Fauci AS, Kasper DL, Longo DL, et al, eds. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008:1021-1027.

6. Simon HB. Infections due to mycobacterium. In: Dale DC, Federman DD, Antman K, et al, eds. ACP Medicine. New York, NY: WebMD Professional Publishing; 2004:1703-1720.

7. Baker LP. Mycobacterium leprae interactions with the host cell: recent advances. Indian J Med Res. 2006;123:748-759.

8. Ishii N. Recent advances in the treatment of leprosy. Dermatol Online J. 2003;9:5. http://dermatology.cdlib.org/92/reviews/leprosy/ishii.html. Accessed March 16, 2015.

9. World Health Organization. Global leprosy situation, 2012. Weekly Epidemiological Rec. 2013;88:365-380. http://www.who.int/wer/2007/wer8835.pdf. Accessed March 16, 2015.

10. Gelber RH. Hansen disease. West J Med. 1993;158:583-590.

11. Deps PD, Alves L, Gripp CG, et al. Contact with armadillos increases the risk of leprosy in Brazil: a case control study. Indian J Dermatol Venereol Leprol. 2008;74:338-342.

12. Booth AV, Kovich OI. Lepromatous leprosy. Dermatol Online J. 2007;13:9.

13. Yens DA, Asters DJ, Teitel A. Subcutaneous nodules and joint deformity in leprosy. Clin Rheumatol. 2003;9:181-186.

14. Panezai S, Saleh FG. Leprosy and peripheral neuropathy. J Clin Neuromuscul Dis. 2004;5:138-145.

15. Sasaki S, Takeshita F, Okuda K, et al. Mycobacterium leprae and leprosy. Microbiol Immunol. 2001;45:729-736.

16. Kumar A, Girdhar A, Chakma J, et al. WHO Multidrug Therapy for Leprosy: Epidemiology of default in treatment in Agra District, Uttar Pradesh, India. BioMed Research International. doi:10.1155/2015/705804.

17. Fiallo P, Clapasson A, Favre A, et al. Overexpression of vascular endothelial growth factor and its endothelial cell receptor KDR in type I leprosy reaction. Am J Med Hyg. 2002;66:180-185.

18. Sales AM, de Matos HJ, Nery JAC, et al. Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy. Braz J Med Biol Res. 2007;40:243-248.

19. Lockwood DN, Colston MJ, Khanolkar-Young SR. The detection of Mycobacterium leprae protein and carbohydrate antigens in skin and nerve from leprosy patients with type I (reversal) reactions. Am J Trop Med Hyg. 2002;66:409-415.

20. Boggild AK, Keystone JS, Kain KC. Leprosy: a primer for Canadian physicians. CMAJ. 2004;170:71-78.

21. Rook GA, Baker R. Cortisol metabolism, cortisol sensitivity and the pathogenesis of leprosy reactions. Trop Med Int Health. 1999;4:493-498.

Treatment Options

Treatment of leprosy typically involves multidrug therapy. There are several effective chemotherapeutic agents against M leprae, including dapsone, clofazimine, ofloxacin, and minocycline.¹⁵ The World Health Organization recommendations for treatment are based on the classification of patient disease as either multibacillary or paucibacillary.¹⁶ Currently, patients are classified as multibacillary if they have 6 or more skin lesions and paucibacillary if they have fewer than 6 lesions.⁵ World Health Organization recommendations for paucibacillary leprosy include monthly doses of rifampin along with daily doses of dapsone for 6 months. Multibacillary patients usually are treated with a combination of rifampin, dapsone, and clofazimine for 12 months.¹

Management of Reversal Reactions

Leprosy reactions can occur in all leprosy patients most commonly during multidrug therapy and represent a delayed hypersensitivity response to M leprae antigens.¹⁷ Type 1 and 2 reactions together affect 40% to 50% of all patients at least once during their disease course. Type 1 reactions occur in patients in the tuberculoid and borderline portion of the spectrum. These reactions manifest as erythema and induration of existing plaques. Frequently, progressive neuritis leads to sensory and motor neuropathy. These type 1 reactions typically develop gradually and may last for several weeks.⁴ Type 2 reactions occur in patients with borderline lepromatous leprosy and lepromatous leprosy and are characterized by the appearance of tender, erythematous, subcutaneous nodules. They are often accompanied by systemic symptoms such as malaise, fever, edema, arthralgia, and weight loss. Organ systems including the joints, eyes, testes, and nervous system also may be affected.¹⁸ The natural course of a type 2 reaction is 1 to 2 weeks, but many patients experience multiple recurrences over several months.

All leprosy reactions are believed to be immunologically mediated; however, the mechanism responsible for each reaction type remains poorly defined. The histology of type 1 reactions is that of a delayed-type hypersensitivity response with CD4⁺ T cells, macrophages, and expression of IL-2 in lesions. In type 1 reactions, increases in cytokines including IL-1, IL-2, IL-12, IFN-γ, and tumor necrosis factor a have been documented both locally within the skin and systemically in the serum. However, studies have not been able to differentiate if this enhanced T_H1 response is related to an immunological versus an inflammatory process.¹⁹

Type 2 leprosy reactions occur in patients with poor cellular immunity to M leprae. The acute lesions typically are characterized by a neutrophilic infiltrate superimposed on a chronic lepromatous pattern, and there is a systemic inflammatory response to immune complex deposition. It has been proposed that type 2 leprosy reactions are a type of Arthus reaction characterized by deposition of an immunoglobulin-antigen complex in vascular endothelium with subsequent complement activation. Both immunoglobulin and complement have been demonstrated in the reactive nodules of type 2 reactions, and serum complement is decreased in these patients, supporting this pathogenic process.⁴ Other studies have identified possible immune cell activation in type 2 reactions, including increases in T_H2-related cytokines.¹⁹

These immunologic reactions can ultimately lead to impaired motor, sensory, and autonomic nerve function if allowed to progress.²⁰ As a result, anesthetic limbs are subjected to repeated trauma, infection, and pressure necrosis that may lead to limb deformity. Autonomic nerve dysfunction may lead to loss of the corneal reflex, which can result in blindness. Common motor findings include wrist and foot drop as well as clawing of the hand from damage to the nerves of the upper extremity.²⁰

Treatment of both type 1 and 2 leprosy reactions is imperative, as these inflammatory reactions are responsible for a great deal of the permanent nerve damage, deformity, and disability that is associated with leprosy.²¹ Oral and intralesional corticosteroids typically are highly effective for the clinical treatment of type 1 and 2 leprosy reactions given their anti-inflammatory properties. Our patient’s type 1 leprosy reaction responded well to intralesional corticosteroid injections. Thalidomide also has proven to be highly effective in treating type 2 reactions and was used frequently prior to realization of its teratogenic effects. It is now prohibited for use in women of childbearing age but is still routinely used in many countries for the treatment of type 2 reactions in men and postmenopausal women. Other therapies for type 2 reactions that have been used with some success include cyclosporine, azathioprine, and pentoxifylline.⁴

Conclusion

In summary, we present a unique case of multiple cutaneous reversal reactions in a patient with leprosy years after successful antimicrobial therapy. Proper recognition of this phenomenon is important to avoid overtreatment for mistaken recurrent disease. Although rare in the United States, leprosy should be considered in the differential diagnosis of patients presenting with hypoesthetic or anesthetic skin lesions, chronic annular dermatitis, papular or nodular granulomatous skin lesions, diffuse cutaneous infiltrative disease, peripheral neuropathy, and a history of travel to regions where the disease is known to be endemic. Additionally, if left untreated, M leprae infection and subsequent type 1 or type 2 reactions can lead to devastating neurologic and cutaneous sequelae. Prompt recognition and treatment of these reactions is imperative to prevent these long-term complications.