American Journal of Dermatopathology:
Letter to the Editor
*Department of Dermatology, Medical University of Graz, Graz, Austria; †Unit of Social Dermatology, National Reference Center for Hansen's Disease, Azienda Ospedaliera Universitaria “San Martino” di Genova and Department of Health Sciences, University of Genoa, Italy; and ‡Department of Dermatology, Medical University of Graz, Graz, Austria.
To the Editor:
Rongioletti et al,1 in a recent case report, underlined the problem of leprosy diagnosis in nonendemic areas like Europe. We would like to report 3 additional cases that illustrate very well how in nonendemic countries both dermatologists and dermatopathologists often lack specific experience, with potentially harmful delay in patient's treatment. In this context, we would like to underline that in Italy (like in many other European Countries) the official resident immigrant population increased from 1,549,373 units in 2002 to 3,432,651 units in 2007 (data available at http://demo.istat.it/). Many other immigrants, however, do not appear in the official statistics, and the real number probably exceeds 4-5 millions units. In the years 2002-2008, the National Reference Center for Hansen's Disease (HD) in Genoa reported 64 new leprosy cases: 6 patients were Italians (5 infected during periods spent in endemic countries, 1 autoctonous) and 58 were immigrants from Africa (16 cases), South America (19 cases), and Asia (23 cases), respectively. In the first 6 months of 2009 alone, 9 new cases have been observed. These data clearly show that leprosy is not infrequent also in nonendemic countries, mainly due to immigration flows.
In the last few months, 3 immigrant patients from areas endemic for HD have been sent for consultation to the National Reference Center for HD in Genoa from different departments of Italy. All patients had been sent without a specific diagnosis and only because of the clinical history of immigration from endemic countries. Biopsy specimens had been taken, processed, and reported at the original departments, but leprosy had not been included in the differential diagnoses. After clinical reevaluation of the patients in the National Reference Center for HD in Genoa, the original biopsies were sent to Graz for second expert opinion. Patient 1 (28-year-old man, immigrant from Nigeria) was biopsied for the presence of “unclear small nodules on the face.” Histology showed a nodular dermal infiltrate without involvement of the epidermis. The infiltrate was composed by foamy macrophages, many of which showing giant, bizarre intracytoplasmic vacuoles (Fig. 1). The original histopathologic diagnosis was “unusual xanthoma.” A Fite stain (previously not done) disclosed large numbers of solid bacilli forming typical “globi.” Patient 2 (22-year-old man, immigrant from Colombia) presented with multiple nodules on the extremities and was biopsied without a specific clinical diagnosis. Histology showed a dermal, patchy-nodular infiltrate with a grenz zone; the infiltrate was composed of foamy macrophages and lymphocytes (Fig. 2). A Fite stain had disclosed numerous single solid bacilli and globi; however, a diagnosis of “unclear atypical mycobacterial infection” had been made (Fig. 3). Patient 3 (14-year-old boy, immigrant from Brazil) presented with multiple symmetric hypopigmented macules on the entire body, and was biopsied with the clinical differential diagnosis of pityriasis alba versus pityriasis versicolor (Fig. 4). In this case, too, the biopsy specimen showed a patchy-nodular infiltrate with vacuolated macrophages, many of which presenting giant vacuoles. Fite stain was clearly positive for solid bacilli and “globi,” but the original histopathologic diagnosis was of “nontubercular mycobacterial infection.” Interestingly, this child had been treated for 1 year for atopic dermatitis and pityriasis versicolor before being referred to the National Reference Center for HD in Genoa.
In patient 1, the correct histologic diagnosis of lepromatous leprosy probably had been simply overlooked, as a Fite stain had not been performed at all.2-4 In patients 2 and 3, experience in histopathologic features of leprosy was lacking, and despite a positive Fite staining the correct diagnosis had not been made. Moreover, in all 3 patients the clinical diagnosis had been initially missed, too, thus underlying the difficulties for clinicians in making a diagnosis of “tropical” disorders in nonendemic countries.
Original histopathologic misdiagnosis in all of these patients resulted in the delay of appropriate treatment of highly infective patients, with potential harmful consequences both for the patients and the population. Moreover, these cases illustrate the difficulties of both clinical and histopathologic diagnosis of leprosy in nonendemic areas even in typical cases, and not only in patients with more challenging histopathologic features such as the one reported by Rongioletti et al. Concerning the patient presented by Rongioletti et al, we would also like to provide more detailed data, as she is followed in the National Reference Center for HD in Genoa. At first presentation in September 2006, the patient had multiple asymmetrical, oval-annular lesions on her legs, abdomen, and flank, with sensory anesthesia. The biopsy had been taken before referral to the National Reference Center for HD. At clinical investigation upon referral, the right ulnar nerve and the posterior tibial nerve were enlarged and painful. The original slides were reviewed and a skin smear was taken at the border of one lesion on the right leg, showing 2 solid bacilli. Based on these findings, a diagnosis of borderline tuberculoid leprosy was made, and treatment with World Health Organization multidrug therapy for multibacillary leprosy together with prednisolon 25 mg/d was started in October 2006. In February 2007, she developed a type 1 reaction with involvement of the right ulnar nerve and posterior tibial nerve. Prednisolon was increased to 60 mg/d with progressive tapering of the dose. At the last follow-up visit in June 2009, all skin lesions had completely regressed, and only a focal sensory deficit of the right planta was present.
Due to the increment of the immigration flows from endemic areas, leprosy cases might be more frequently observed also in nonendemic areas like Europe. Although HD remains a rare disease, histological confirmation is mandatory in all cases (in Italy it is requested by official guidelines of the Ministry of Health),5 thus representing a potential pitfall for dermatopathologists without specific experience. Dermatologists and dermatopathologists should be aware of HD to properly and timely manage these patients.
Cesare Massone, MD
Department of Dermatology, Medical University of Graz, Graz, Austria
Enrico Nunzi, MD
Unit of Social Dermatology, National Reference Center for Hansen's Disease, Azienda Ospedaliera Universitaria “San Martino” di Genova and Department of Health Sciences, University of Genoa, Italy
Lorenzo Cerroni, MD
Department of Dermatology, Medical University of Graz, Graz, Austria
1. Rongioletti F, Gallo R, Cozzani E, et al. Leprosy: a Diagnostic trap for dermatopathologists in nonendemic area. Am J Dermatopathol
2. Ridley DS. Skin Biopsy in Leprosy
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3. Ridley DS. Histological classification and the immunological spectrum of Leprosy. Bull WHO
4. Lucas SB, Ridley DS. The use of histopathology in leprosy diagnosis and research. Lepr Rev
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5. Nunzi E, Forgione P, Clapasson A, et al. La diagnosi telematica della lebbra. G It Dermatol Venereol