Erythema nodosum leprosum as the presenting feature in multibacillary leprosy
Published Web Locationhttps://doi.org/10.5070/D34066k678
Erythema nodosum leprosum as the presenting feature in multibacillary leprosy1. Associate Professor, Dept. of Skin & STD, Kasturba Medical College, Manipal, India. firstname.lastname@example.org, email@example.com
Smitha Prabhu MD DVD1, S D Shenoi MD DVD2, Sathish Pai B MD DVD2, Sripathi H DVD DNB1
Dermatology Online Journal 15 (6): 15
2. Professor, Dept. of Skin & STD, Kasturba Medical College, Manipal, India
Leprosy is an ancient disease that has survived into the modern ages despite an intense effort to eliminate it worldwide. Here we report a case of a 32-year-old woman who had recurrent painful nodules of six months duration. Because of a lack of lesions suggestive of leprosy, she was initially diagnosed to have cutaneous vasculitis and erythema nodosum. However, because of the persistent nature of her condition she was later detected to have leprosy and erythema nodosum leprosum (ENL) with the aid of simple diagnostic tests.
Leprosy or Hansen disease is still a scourge in many parts of the world, especially in India, Burma, Nepal, and some areas of South East Asia. Leprosy is a unique disease with a peculiarly long incubation period, a wide spectrum of clinical presentations related to host immunity, and the tendency for debilitating acute exacerbations, termed reactions. Here we present a 32-year-old woman with multiple tender erythematous nodules of six months duration, initially diagnosed as erythema nodosum; she was subsequently detected to have Hansen disease.
A 32-year-old woman presented to us with recurrent painful, red raised cutaneous nodules of six months duration, which first occurred on the palms and spread to other areas. The nodules typically subsided in one week's time after taking oral prednisolone prescribed by a local doctor. She also had multiple joint pains, fever, anxiety, weight gain, and fatigue. She did not complain of photosensitivity, muscle weakness, or sensory or motor loss.
|Figure 1||Figure 2|
|Figure 1. Fleshy erythematous nodule on nose|
Figure 2. Erythematous tender nodules and plaques over forearms
On examination, she had subcutaneous, tender, erythematous blanching nodules on arms, forearms, legs, face, palms, and soles. A few nodules were crusted with serosanguinous discharge. Post-inflammatory pigmentation was present on trunk, legs, and arms. There were no other patches, plaques or nodules. There was bilateral pitting pedal edema and loss of temperature sensation on the extremities in a patchy glove and stocking pattern. Bilateral ulnar and radial cutaneous nerves were thickened and tender. All blood investigations including complete blood count, liver and renal function tests, and glucose levels were normal, except for a high ESR of 96 mm/hr.
|Figure 3||Figure 4|
|Figure 3. Erythematous nodules over thigh|
Figure 4. Slit skin smear specimen reveals groups of acid fast bacilli. (Z-N stain, x40)
Skin smears taken from nodules and stained with Ziehl-Nielssen stain revealed a bacterial index of 4+ and morphological index was 1 percent.
A punch skin biopsy from a representative nodule showed a hyperkeratotic and acanthotic epidermis overlying an edematous dermis with capillaries showing endothelial swelling with perivascular and periadnexal lymphoplasmacytic infiltrate and neutrophils. Subcutaneous fat showed lobular panniculitis characterized by perivascular lymphocytes, eosinophils, and histiocytes.
She was diagnosed with multibacillary (MB) leprosy with erythema nodosum leprosum (ENL). Treatment was initiated with multibacillary multi drug therapy (monthly rifampicin 600 mg, monthly clofazimine 300 mg along with daily clofazimine and dapsone, 50 mg and 100 mg, respectively) for the MB leprosy. In addition, for the ENL, prednisolone 40 mg/day was begun (with the plan to be tapered and stopped in a 3-month period) along with thalidomide 300 mg per day and analgesics. At her subsequent follow-up at one month, all nodules had subsided, but she had developed a cushingoid facies.
Erythema nodosum leprosum (ENL) or Type 2 leprosy reaction is an acute reaction state in the chronic course of lepromatous leprosy and its subsets. It occurs in up to 25 percent of lepromatous cases , usually during or after treatment. However, some cases have been reported even before starting treatment  or as the first clinical manifestation of leprosy. It is a multisystem disorder involving skin, peripheral nerves, and sometimes, the internal organs. It presents in the skin as crops of painful or tender, evanescent, erythematous nodules, concentrated on the extremities, which may sometimes become bullous or ulcerated. The condition is often accompanied by fever, neuritis, and inflammation of internal organs in varying degrees. Histologically, it is characterized by necrotizing vasculitis of the vessels of the deep dermis and subcutis . The pathogenesis of ENL involves immune complex deposition and dysfunction of cell mediated immunity. Activation of complement and migration of neutrophils with release of tissue damaging enzymes, including IL-12 and TNF-α are important factors in the evolution of the disease. Such patients have poor cellular immunity to M. leprae, abundant bacilli in cutaneous and peripheral nerves, and a strong polyclonal antibody response with high levels of circulating immunoglobulins . The triggers of Type 2 reaction include other illnesses, mental or physical stress, and immunizations. Arbitrarily, ENL has been classified into variants: acute single (i.e., single episode of ENL lasting less than 6 months and not recurring on steroid tapering), acute multiple (more than one episode of ENL in 6 months), and chronic (one episode of ENL lasting for more than 6 months) .
Because the pathogenesis involves immune complex deposition and cell mediated immunity defects, immunosuppressants and TNF-α inhibitors have a role in treatment. Thalidomide and corticosteroids are the mainstays of treatment, though various other modalities such as clofazimine, azathioprine, pentoxifylline, cyclosporine, methotrexate , antimony compounds, colchicines, chloroquine, levamisole, zinc, and plasmapheresis have been used . Newer drugs including TNF-alpha inhibitors, IV Immunoglobulins, and the new non-steroidal anti-inflammatory drug, Tenidap, show promise .
Erythema nodosum leprosum that occurs as the first manifestation of lepromatous or borderline lepromatous leprosy has been described by very few authors [7, 8]. The occurrence of ENL in the absence of skin lesions of leprosy may lead to a delay in diagnosis. This condition has to be considered in the differential diagnosis of other diseases with tender nodules such as erythema nodosum, other panniculitides, Sweet syndrome, and nodular vasculitis.
Our patient is quite interesting because the patient presented with ENL lesions associated with fever and neuritis and was found to have glove and stocking sensory loss, but there were no primary skin lesions suggestive of Hansen disease, although there was marked skin involvement with lepra bacilli as is seen in Lucio leprosy (lepra bonito). These patients may also present with skin numbness, particularly of hands and feet, and madarosis (loss of eyelashes and eyebrows). We hypothesize that ENL occurred as the first manifestation of silent lepromatous leprosy. Some authors conclude that the absence of chronic skin lesions of leprosy in such cases may be due the complete lack of a TH1 immune response, which leads to a high intra-macrophage bacillary load and a TH2-mediated overproduction of specific antibodies. In such patients, if there is any switch to a TH1 response, a massive extracellular release of mycobacterial antigens from macrophages makes these available to bind with their specific antibodies and cause severe immune complex-mediated type III hypersensitivity responses that produce neuritis and ENL lesions in the skin .
Recurrence of tender, red nodules in people in endemic areas should always prompt the treating physician to rule out leprosy by simple clinical and laboratory tests.
References1. Pocaterra L, Jain S, Reddy R, Muzaffarullah S et al. Clinical course of Erythema nodosum leprosum: an 11-year cohort study in Hyderabad, India. Am J Trop Med Hyg 2006;74:868-79 [PubMed]
2. Rea TH and Levan NE. Erythema nodosum leprosum in a general hospital. Arch Dermatol 1975;111: 1575-80. [PubMed]
3. Cuevas J, Rodriguez-Peralto JL, Carrillo R and Contreras F. Erythema nodosum leprosum: reactional leprosy. Semin Cutan Med Surg 2007;26:126-30 [PubMed]
4. Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, et al. The continuing challenges of leprosy. Clin Microbiol Rev 2006;19:338-81 [PubMed]
5. Girdhar BK. Immunopharmacology of drugs used in leprosy reactions. Ind J Dermatol Venereol Leprol 1990;56:354-63
6. van Veen NHJ, Lockwood DNJ, van Brakel WH, Ramirez Jr J, Richardus JH. Interventions for erythema nodosum leprosum. (Protocol) Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD006949. DOI: 10.1002/14651858.CD006949
7. Tourlaki A, Marzano AV, Gianotti R, Fiallo P, et al. Necrotic erythema nodosum leprosum as the first manifestation of borderline lepromatous leprosy. Arch Dermatol 2008;144:818-20. [PubMed]
8. Wong WS. Leprosy presenting as nodular vasculitis. Br J Rheumatol 1987;26:398. [PubMed]
9. Andreoli A, Brett SJ, Draper P, Payne SN, et al. Changes in circulating antibody levels to the major phenolic glycolipid during erythema nodosum leprosum in leprosy patients. Int J Lepr Other Mycobact Dis 1985;53:211-17 [PubMed]
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