Reactions in Hansen’s Disease

Summary of iH Teaches

by Claudio Sampieri Tonello.

Dermatologist.Head of the Service of Training in Dermatology, Instituto Lauro de Souza Lima, Bauru, São Paulo, Brazil.

Hansen's disease (HD) is a chronic infectious disease with clinical manifestations that appear slowly during the course of its natural evolution. Reactions in HD are acute phenomena that occur during this evolution, and can occur in all clinical forms of HD except the initial ‘indeterminate’ form [1].

Reactions in HD can be cell-mediated in the tuberculoid and borderline forms (type 1 reaction) or antibody-mediated in the virchowian (lepromatous) form (type 2 reaction - also called erythema nodosum leprosum) [1]. They can appear before the diagnosis of the disease, during treatment, and even after discharge [3].

Around 30-50% of people affected by HD show some type of reaction during the course of the disease. There is also a third rare type of reaction, called Lucio's phenomenon, which occurs in patients affected by the diffuse non-papular nodular virchowian form of HD [2].

Type 1 reactions

The main characteristic of a type 1 reaction is the exacerbation of pre-existing skin lesions and the appearance of new lesions in a relatively acute form. These are usually well-defined erythemato-edematous plaques that may ulcerate (tuberculoid). Peripheral nerves can be affected, causing neuritis, with increased pain [1,3]. The patient’s general clinical status may be affected, with edema of the extremities and involvement of more than one peripheral nerve, especially in borderline forms of HD.

Type 1 reactions are delayed cellular hypersensitivity reactions resulting from an increased cellular response against M. leprae [2]. The risk of nerve damage and disability demand that treatment of type 1 reactions starts as soon as possible. A type 1 reactional outbreak typically lasts 4-6 months, regardless of treatment [1].

Histologically, a granulomatous inflammatory reaction with tuberculoid or borderline pattern is observed, sometimes associated with exudative phenomena with edema, fibrin deposition, and tissue necrosis [3].

If there are no neurological manifestations, type 1 reactions can be treated symptomatically. If neuritis or exuberant skin lesions occur, systemic steroids should be prescribed, usually oral prednisone 1mg/kg/day. The use of corticosteroids in type 1 reaction should always be planned and scheduled, with gradual reduction of the medication. Type 1 reactions last typically 4-6 months therefore, patients will be treated with prednisone for not less than 4 months [3]. Usually, prednisone is withdrawn gradually every 2-4 weeks, with follow-up guided by clinical and sensory-motor tests [4]. Other immunosuppressive drugs (methotrexate, cyclosporine) may eventually be used [3,5]. Some patients develop several flare-ups of type 1 reaction during the course of the disease, requiring repeat treatment. Unfortunately, no effective treatment is known to stop a type 1 reaction outbreak after its onset [1].

Type 2 reactions

Of the type 2 reactions, erythema nodosum leprosum (ENL) is the most well-known. ENL is a systemic phenomenon characterized by the sudden appearance of painful erythematous nodules, papules and plaques on the skin [1]; after regression, fibrosis, scarring and post-inflammatory hyperpigmentation may appear. Triggering factors include pregnancy, vaccination, emotional stress, and other acute bacterial or viral infections.

In general, type 2 reactions occur after the start of multidrug therapy (MDT) for HD, but it can also occur after discharge following the end of MDT treatment. However, many patients develop type 2 reactions before treatment, and, in this case, the diagnosis of HD is made during this reaction phenomenon. Patients with a high bacillary load can have leprosy reactions for a longer time (years), probably because of the presence of antigens in tissues. Type 2 reactions are of shorter duration and have a higher rate of occurrence than type 1 reactions [3].

A typical type 2 reaction begins with fever, malaise, loss of appetite, arthralgia and lymph node enlargement, followed by cutaneous manifestations with erythematous, sometimes painful nodules. Peripheral nerves, eyes, joints, liver, testes and spleen, can be compromised during a type 2 reaction [1]. Type 2 reactions arise from the formation and deposition of immunocomplexes that occur because of the large amount of antibodies present in virchowian patients.

Histological changes represent an acute or subacute inflammatory reaction (therefore, not granulomatous) in foci of regressive virchowian granulomas, vascular dilatation, endothelial tumefaction, and serofibrinous and neutrophilic exudation disorganizing any pre-existing granulomas [1].

Thalidomide is the drug of first choice for the treatment of type 2 reactions, albeit contraindicated in women of childbearing age because of its teratogenic effects. The dose used varies from 100-400 mg per day depending on the severity of the reaction. In general, the response to thalidomide is rapid, allowing for dosage to be reduced after signs and symptoms improve, usually within a few days or weeks. Whenever there are important general symptoms, more severe reactions or other organs are affected, the use of systemic corticosteroids is indicated, such as oral prednisone at a dose of 1mg/kg/day. Formal indications for the use of corticosteroids in type 2 reactions are severe ENL, neuritis, iritis or iridocyclitis, and involvement of hands.

Final considerations

1. The treatment of HD reactions does not interfere with the MDT regimen.

2. Many patients continue to have HD reactions after being discharged or discontinuing MDT.

3. Patients with HD reactions after being discharged may be misdiagnosed with drug resistance and/or HD relapse.

4. HD reactions after discharge are immunological and inflammatory conditions, not the infectious disease, and may persist for months to years.

5. Patients with persistent and/or delayed HD reactions (after being discharged) must be evaluated for persistent bacilli. To evaluate the possibility of reinfection, it is important to examine household contacts and to look for undiagnosed and untreated contacts with hidden HD who may be a source of bacilli for the index case.

6. Patients with HD reactions require management and follow-up by a multiprofessional team.

IH Editorial Board :

Patrícia D. Deps and José Antônio Garbino.


Thauyra Isis Aparecida de Oliveira, Patrícia D. Deps and Simon M. Collin.


  1. Opromolla DVA. Manifestações clínicas e reações. In: Noções de Hansenologia. 2ª. Ed. Bauru: Centro de Estudos “Dr. Reinaldo Quagliatto”. Instituto Lauro de Souza Cima; 2000.

  2. Kamath S, Vaccaro SA, Rea TH, Ochoa MT. Recognizing and managing the immunologic reactions in leprosy. J Am Acad Dermatol. 2014 Oct;71(4):795-803. doi: 10.1016/j.jaad.2014.03.034.

  3. Ura S. Tratamento e controle das reações hansênicas. Hansen Int. 2007; 32(1):67-7.

  4. Ministério da Saúde do Brasil. Guia Prático Sobre a Hanseníase. 2017. Accessed at: Acessado em 19 de agosto de 2021.

  5. Perez-Molina JA, Arce-Garcia O, Chamorro-Tojeiro S, Norman F, Monge-Maillo B, Comeche B, Lopez-Velez R. Use of methotrexate for leprosy reactions. Experience of a referral center and systematic review of the literature. Travel Med Infect Dis. 2020 Sep-Oct;37:101670. doi: 10.1016/j.tmaid.2020.101670.