Abstract

Leprosy is currently uncommon in Europe: the diagnosed cases are almost allimported from endemic areas. We report on an autochthonous case of borderline lepromatous leprosy in a 71 year-old Portuguese woman. The case was complicated by a reversal reaction and then by erythema nodosum leprosum. A review of the literature identified 18 reported cases of European autochthonous leprosy since 2000, all but one were observed in Mediterranean countries. Active clusters of leprosy therefore persist in Europe particularly in Spain, Greece, Portugal and Italy.

KeywordsIntroductionAccording to the World Health Organisation (WHO), approximately 210 000 new cases of leprosy are identified worldwide each year [[1]

WHO. Global leprosy update, 2018: Moving towards a leprosy-free world. Available from: https://www.who.int/publications-detail-redirect/who-wer9435-36/, Wkly Epidemiol Rec 2019;94:389–412 (accessed 15 April 2021).

]. This infection affects the skin and peripheral nervous system. Clinical presentation depends on the host's immunological status towards Mycobacterium leprae [[2]

Britton WJ, Lockwood DNJ. Leprosy. Lancet 2004;363:1209‑19. https://doi.org/10.1016/S0140-6736(04)15952-7.

]. Leprosy has become rare in Europe since the second half of the 20th century due to the era of multi-drug therapy. For example in Germany, where leprosy is a notifiable disease, only 29 cases were reported between 2001 and 2015 [[3]Becker SL Mawlood DA Janssen A Heinricy L Janssen E Vogt T et al.Multibacillary leprosy in a migrant from Afghanistan: A disease not to be forgotten.]. The few cases diagnosed in Europe are almost all imported from endemic areas [[4]Beltrame A Barabino G Wei Y Clapasson A Orza P Perandin F et al.Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018.]. In most cases, there is a diagnostic delay due to low physician awareness of the disease.

Here, we report on an autochthonous case of borderline-lepromatous leprosy in a European woman, which initially presented as a diagnostic dilemma.

Case report

A healthy 71-year-old Portuguese woman was referred by her private dermatologist to our department with a three-year history of intermittently flaring chronic maculopapular dermatosis of the chest, abdomen and limbs. She was on statins and levothyroxine for hypercholesterolemia and hypothyroidism, respectively. She had never travelled outside Portugal and France.

A clinical examination revealed a large number of erythematous macules and papules, somewhat pruritic but not hypoaesthetic. Some of the lesions were ring-shaped. (Fig. 1A). The patient did not report any neurological symptom. Laboratory tests evidenced an elevated serum level of angiotensin-converting enzyme (82 IU, NFig. 1B). An immunohistochemical screen with anti-Mycobacterium antibodies was positive. Therefore, the patient underwent further neurological examination. She was found to have new-onset paraesthesias in her upper and lower limbs and palpation revealed hypertrophy of the ulnar nerve confirmed on ultrasound. Her skin lesions were not hypoaesthetic. Anerve conduction study revealed sensory axonal neuropathy of the limbs without motor impairment . Ophthalmic examination was normal. Ultimately, the Mycobacterium leprae PCR test was positive and identified strain sensitive to antileprotic drugs.

Figure 1A) Borderline-lepromatous leprosy, multiple annular lesions. B) Ziehl-Neelsen staining, intra-cytoplasmic bacilli and globi (arrow). C) Erythema nodosum leprosum (ENL), painful infiltrated nodules.

The WHO-recommended multi-drug therapy (disulone 75 mg/day adjusted for body weight, rifampicin 600 mg/month, Clofazimine 100 mg/day plus an additional 300 mg once amonth) was initiated.

Ten days later, we observed an inflammatory flare-up of the lesions and an increase in paraesthesias.This type 1 reaction responded favorably to systemic corticoid therapy (prednisone, 1 mg/kg).

Fourteen months after the introduction of multi-drug therapy, the patient represented with painful, infiltrated nodules on the anterior aspect of the limbs, fever, and general deterioration. Investigations evidenced an intense inflammatory syndrome (C-reactive protein: 125 mg/L; neutrophilia: 20 G/L). The clinical observations and laboratory results revealed erythema nodosum leprosum (type 2 reaction; Fig. 1C). Initiation of treatment withthalidomide resolved the symptoms rapidly.

The course of multi-drug therapy lasted for a total of 24 months. The patient continues to have follow-up in our department, and we now consider that she has been cured.

Discussion

Our diagnosis of the present case of leprosy was complicated by the initial absence of neurological symptoms, and by the fact that the patient had not travelled to an endemic country.

At the first consultation the patient did not report any neurological symptoms, paraesthesia appeared only 3 years after the first skin lesions. The initial absence of neurological symptoms in (borderline) lepromatous leprosy could be explained by the fact that the neurological lesions are a consequence of the host's inflammatory response to Mycobacterium leprae rather than direct bacillus induced lesions [[5]Spierings E De Boer T Zulianello L Ottenhoff TH. The role of Schwann cells, T cells and Mycobacterium leprae in the immunopathogenesis of nerve damage in leprosy.].

The initial source of our patient's infection could not be found. She could not remember any sick contacts as far back as her childhood, and she had never travelled outside France or Portugal.

The incidence of autochthonous leprosy in Europe is poorly understood. We undertook a literature review in PubMed in order to evaluate where autochthonous cases persist in Europe since 2000 . As search equation we used the terms (leprosy)[Title/Abstract] OR (Hansen's disease)[Title/Abstract] OR (M.leprae)[Title/Abstract]. Articles published from January 2000 to August 2020 were included in the study. The research was limited to “Case Reports” in English, French and Spanish. Articles published by European health services were screened and those specifically relating to new autochthonous cases of leprosy were retained [[6]Norman FF Fanciulli C Pérez-Molina J-A Monge-Maillo B López-Vélez R. Imported and autochthonous leprosy presenting in Madrid (1989-2015): A case series and review of the literature.,[7]Gómez-Camarasa C Rodríguez-Granger J Cañadas-Moreno O Sampedro A Aliaga-Martínez L Cobo F. Autochthonous lepromatous leprosy in a Spanish woman with burns on both feet and skin lesions.,[8]Serrano-Pozo A Gómez-Aranda F Giles M Chinchón D Chinchón I Bautista-Lorite J. Sensory polyneuropathy as initial manifestation of endemic leprosy in Spain.,[9]Lydakis C Ioannidou D Koumpa I Giannikaki E Thalassinos E Krasoudaki E et al.Development of lepromatous leprosy following etanercept treatment for arthritis.,[10]Neonakis IK Gitti Z Kontos F Baritaki S Zerva L Krambovitis E et al.Report of 2 indigenous cases of leprosy from a European country: use of polymerase chain reaction-restriction fragment length polymorphism analysis of hsp65 gene for identification of Mycobacterium leprae directly from a clinical sample.,[11]Ezzedine K Malvy D Beylot C Longy-Boursier M. Autochthonous leprosy in metropolitan France presenting with a diffuse infiltration of the face and febrile illness.,[12]Sampaio L Silva L Terroso G Pimenta S Brandão F Pinto J et al.Hansen's disease mimicking a systemic vasculitis.,[13]Liguori R Terlizzi R Giannoccaro MP Amati A Foschini MP Parodi A et al.An inflammatory myopathy unmasks a case of leprosy in an Italian patient.,[14]Massone C Clapasson A Nunzi E. Borderline lepromatous leprosy in an Italian man.,[15]Achilles E-G Hagel C Vierbuchen M Dietrich M. Leprosy accidentally transmitted from a patient to a surgeon in a nonendemic area.]. A secondary search of the references was performed to identify additional cases [[16]Active leprosy in Greece: a 20-year survey (1988-2007).,[17]Contreras-Steyls M López-Navarro N Herrera-Acosta E Castillo R Ruiz del Portal G Bosch RJ et al.The current challenge of imported leprosy in Spain: a study of 7 cases.].We found 12 articles (8 case reports, 4 case series), reporting 18 cases of autochthonous incident leprosy in Europe, The median publication year was 2011, and the interquartile range (IQR) was 2009-2015. Countries of contamination were Spain (7 cases), Greece (6 cases), Portugal (2 cases), Italy (2 cases), and Germany (1 case). Apart from the case in Germany (a surgeon contaminated by blood exposure), all the autochthonous cases were contaminated in Mediterranean countries. This suggests that clusters of the disease persist in these countries, especially in Portugal, where our patient may have been exposed. The patients’ median age was 55 (IQR: 49 -73), which is greater than the median age of 33 for imported leprosy [[4]Beltrame A Barabino G Wei Y Clapasson A Orza P Perandin F et al.Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018.]. We found a sex-ratio of 1.67 (Men 62.5%, 10 cases; Women 37.5%, 6 cases). There were 10 cases (77%) of multi-bacillary leprosy and 3 cases (23%) of pauci-bacillary leprosy. Type-1 reactions were reported in 2 cases, and type-2 reactions were reported in 4 cases. The median time interval between symptoms onset and diagnosis was 3.0 years (IQR: 2 - 5.5; mean: 8.6 years); these values are greater than the median of 12 months [[4]Beltrame A Barabino G Wei Y Clapasson A Orza P Perandin F et al.Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018.] and the mean of 2.1 years [[5]Spierings E De Boer T Zulianello L Ottenhoff TH. The role of Schwann cells, T cells and Mycobacterium leprae in the immunopathogenesis of nerve damage in leprosy.] reported for the cases imported in Europe. This could be explained by the low level of clinical suspicion for the disease in European populations.

The present case indicates that autochthonous leprosy has not disappeared in European. Physicians should be aware of this, because late diagnosis increases morbidity and the risk of disease transmission.

Declaration of Competing Interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval

Approval was not required.

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Actas Dermosifiliogr. 102: 106‑13https://doi.org/10.1016/j.ad.2010.10.008Article InfoPublication History

Accepted: July 9, 2021

Received in revised form: July 8, 2021

Received: May 30, 2021

Publication stageIn Press Journal Pre-ProofIdentification

DOI: https://doi.org/10.1016/j.ijid.2021.07.023

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