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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.77 no.5 Rio de Janeiro Sept./Oct. 2002
Leprosy combined with elastolytic granuloma*
Aryon de Almeida Barbosa JrI; Newton Sales GuimarãesII; Ivonise FolladorIII; Leila Santos SarnoIV; Constança Pithon PereiraIV
Masters and Ph.D. in Medicine; Titular Researcher at the Fundação
IIAdjunct Professor of Dermatology at the Federal University of Bahia; Dermatopathologist
IIISpecialist in Dermatology by the Brazilian Dermatology Society (SBD). Doctor at the Service of Dermatology at HUPES-UFBa (Professor Edgar Santos University Hospital - Federal University of Bahia)
IVSpecialist in Dermatology by the Brazilian Dermatology Society (SBD)
Two cases of leprosy combined with elastolytic giant cell granuloma are reported. Though a coincidental occurrence cannot be excluded, a possible pathogenetic relationship between the two conditions is postulated. It is possible that an immunological mechanism plays a role in the elastolytic process, which could also be caused by actinic damage in the skin altered by leprosy.
Key words: Granuloma; leprosy
In recent years there has been increased interest in diseases showing degeneration of dermal elastic tissue,1 in spite of the fact that the skin elastic system is not well understood. Some inflammatory and non-inflammatory conditions associated with dermal elastolysis have been described.
The coexistence of leprosy and elastolytic giant cell granuloma, for which we use the term "LEGG", so far as we are aware, has not hitherto been recognized nor described.
The present study documents two unusual cases of leprosy combined with elastolytic giant cell granuloma on exposed areas of skin and discusses their possible relation.
Case 1: a 50-year-old white woman having sun-reactive skin type II from Vitória da Conquista, Bahia, with a long epidemiological history of close contact with a multibacillary leprosy patient, which had had medicamentous hepatitis causing death during the treatment for leprosy.
Patient with a one-year history of progressively spreading crops of non-pruritic, erythematous and edematous plaques and maculae on exposed areas of her skin. Clinical examination revealed multiple erythematous lesions with elevated borders, sometimes of annular aspect on her trunk, décolleté, arms, limbs and earlobes (Figure 1). Almost all of those lesions were of infiltrated aspect. The patient had no subjective symptoms. The cutaneous lesions showed no sensibility alterations. She took no medication. Routine laboratory investigation, including tests for HTLV I and II, was normal. However, the average Bacterial Index (BI) of skin smears was 3.5. The clinical suspicion, before the laboratory examinations, included Borderline Leprosy, Mycosis Fungoides and Erythematous Lupus.
Case 2: a 63-year-old white woman from Salvador, Bahia, developed a cutaneous lesion on her left upper extremity that had begun to develop for two months. Her medical background was unremarkable. Clinically she appeared to be quite well except for the presence of ill defined slightly shinny area with small papules and irregular edges of annular aspect on the flexor surface of her left forearm (Figure 2). The lesion measured about 7x5 Cm in diameter and was the same color as the skin, but showing small areas of hypo pigmentation. There was local thermal sensibility decrease. Findings and results of laboratory examinations were negative or within normal limits, including the BI, which was negative. The clinical suspicion was Tuberculoid Leprosy.
Only one biopsy of each patient was taken in the form of an elliptical biopsy. The biopsies were fixed in 10% formalin for one day. H&E and Fite-Faraco stained histological preparations, sectioned at 5 mm were used to classify and demonstrate M. leprae. Additionally, acid orcein and alcian blue (pH 2.5) stains were performed.
Case 1: skin biopsy from one of the lesions revealed inflammation of neurovascular bundles and skin appendages. Macrophages and lymphocytes were the predominant cell-types. Large number of acid-fast bacilli (AFB) could be seen in the cytoplasm of macrophages, often with foamy aspect (Figure 3). In focal areas of the superficial and mid dermis, sometimes in close proximity to the marked leprosy tissue reaction there was a patchy lymphohistiocytic infiltrate, with many giant cells without vacuoles nor AFB (Figure 4). Elastic fibers were less frequently found in these infiltrates. The few isolated bundles of fibers observed in this area were short and thin. Fragments of elastic fibers were demonstrated within the cytoplasm of a few of the giant cells and macrophages. In the deep reticular dermis, the elastic fibers appeared to be normal. The diagnosis of subpolar lepromatous leprosy combined with elastolytic giant cell granuloma was made.
Case 2: Histological examination of the lesion revealed coexistence of macrophages and multinucleated giant cells that phagocytosed elastic fibers in the upper dermis, causing them to disappear (Figure 5). Besides this lesion, there was perineural inflammation composed mainly of lymphocytes and histiocytes (Figure 6) present either in the deep dermis or in the vicinity of sweat glands. There were scanty demonstrable AFB on nerve bundles, but no Schwann cell proliferation. No significant abnormalities were observed in the epidermis. The diagnosis of indeterminate leprosy combined with elastolytic giant cell granuloma was made.
Treatment and Clinical Course
Once the diagnosis was made, the treatment for leprosy was initiated in both cases. Multidrug Therapy (MDT), as used for multibacillary patients was recommended for patient 1. Patient 2 received a single dose of short-term chemotherapy (ROM). No new lesions appeared in the subsequent twelve months, nor was recurrence observed, during this time the lesions of both patients showed marked improvement.
Elastic fiber degradation or elastolysis, a feature of some cutaneous diseases, constitutes a group of disorders characterized by a decrease or disappearance of dermal elastic tissue. It has been classified as either localized or generalized and may be congenital or acquired with or without systemic manifestations.2 Although elastin, the principal protein constituent of the elastic fibers, comprises only about 2% of the total protein in dermis,3it is physiologically important, providing the resiliency of skin. There are biochemical evidences that elastin is produced by skin fibroblasts.4 Alterations in the elastin structure or metabolism have been implicated in a number of heritable and acquired cutaneous diseases. Although the biochemical basis for the observed changes in the elastin structure is not known, elastase-a proteolytic enzyme- has been thought to be involved in the process, sometimes stimulated by cathepsin G.5 Moreover, the interaction of elastase with elastin depends on electrostatic forces.6 The pathogenic mechanisms of elastolysis are poorly understood. Defects in synthesis of elastic tissue, release of elastase by inflammatory tissue, decrease in serum copper, and immune mechanisms have been postulated as possible mechanisms. Although it is not clear whether inflammation is a primary event or if it occurs as a phenomenon secondary to the elastolytic process, there is some evidence that inflammation is important in various elastolysis.2
Dermal histiocytic and giant cell phagocytosis of elastic tissue (elastoclasis) is seldom found in several inflammatory dermatoses that may be considered to belong to a clinical spectrum of diseases characterized by a granulomatous infiltrate with elastolysis. Multinucleated giant cells containing elastic fibers are also found in annular granuloma (then known as annular elastolytic giant cell granuloma), actinic keratoses, persistent insect-bite reactions, elastosis perforans serpiginosa, granulomatous syphilis, foreign body granuloma, keratoacanthoma, basal cell carcinoma and certain variants of cutaneous T-cell dyscrasia i.e. granulomatous slack skin and mycosis fungoides;7,8 as well in Adult T cell leukemia,9,10 necrobiosis lipoidica and senil purpura.11 Recently we have seen elastoclasis in a cutaneous lesion from a patient with tegumentar leishmaniasis (unpublished data). Other conditions that need to be considered in the histopathologic differential diagnosis include cutaneous sarcoidosis and deep fungal infections. All these diagnoses may be excluded in our patients. Our specimens showed neither epithelioid tubercles nor numerous lymphocytes and the pathological process also spared the subcutis.
Elastoclasis may occur non-specifically, at least in some cases, in sun-protected areas, as well as in sun-exposed skin.12 Elastic tissue phagocytosis may be, however, a secondary event in several inflammatory dermatoses, with degradation of the elastic fibers that are present within the infiltrate.7,13 AAlternatively, the primary event might be the granulomatous inflammatory reaction directed against elastic fibers, with actinic damage14 or not15 However, the process of elastolysis by multinucleated giant cells has not yet been elucidated and is still uncertain. In elastolytic giant cell granuloma, collagen fibers are not affected.16 Elastic fibers are, however, digested by histiocytes and multinucleated giant cells, therefore, in the post reactive central zone, the collagen fibers are intact and the elastic fibers are absent.14,17,18,19 Yanagihara et al, 1987,16 suggested that the elastolytic process in this disease proceeds in two steps: an extracellular digestion and an intracellular digestion of the elastic fibers.
The purely descriptive term elastolytic giant cell granuloma (EGCG), was introduced to overcome inadequacies in the previous terminology.15 The lack of uniformity in terms of terminology can be attributed to an overlap of clinical and histopathological features20 and uncertainty with regard to its etiology. Its histologic features include granulomatous infiltration by many giant cells (often with asteroid body formation), histiocytes, lymphocytes, scattered epithelioid cells, and no necrobiosis. Elastic tissue appears to disappear at the borders of the granuloma and is totally absent in the center. EGCG is an uncommon entity that may not be readily recognized by the uninitiated. The recognition of this disease in this region of the world is especially important since it may be misdiagnosed as tuberculoid leprosy. It is therefore useful to recognize the pattern of granulomatous elastolysis, lest it be confused with other forms of granulomatous dermatitis. Accordingly, an additional component of the diagnostic algorithm in approaching granulomatous dermatitis is to determine whether elastic fiber phagocytosis is a prominent feature of the histiocytic response.8
The special interest of the presented cases is that the clinical findings, including the localization and the pathological findings, were uncommon. In patient 2, the clinical aspect of the lesion, corresponding to the superficial elastolytic granuloma, induced the clinician to suspect of Tuberculoid Leprosy. It is widely recognized that the diagnosis of leprosy is often difficult. But the coexistence of leprosy and elastolytic giant cell granuloma (LEGG), could be a source of worry and may pose further a challenge for pathologists. In spite of the recognition of leprosy, one could well misinterpretate the leprosy form. The granulomatous appearance of the lesion, with elastophagocytosing giant cells, might suggest a diagnosis of paucibacillary leprosy (tuberculoid or borderline tuberculoid) and so induce to inappropriate treatment.
To our knowledge, there are no clinico-pathological descriptions of similar cases with the recognition of elastoclasis. Rueda & Rodriguez reported, in 1979,21 a group of 16 patients of both sexes, having lepromatous leprosy with giant cells, some of which containing asteroid bodies. Although they referred to these case as "Giant Cell Lepromatous Leprosy", and the incorporation of dermal elastic fibers into the cytoplasm of the histiocytes and giant cells was not demonstrated by means of elastica staining, according to one of us (AABJr), it is likely that at least some of these patients could also be fitted into the same clinico-pathological picture of LEGG.
The dermal elastic fibers of leprosy patients had characteristic features, depending on the types of leprosy, duration periods of active condition and destroyed dermal strutures.22 The question that arises is as to whether the association of leprosy with elastolytic giant cell granuloma is more than just coincidental. Although the possibility that the two lesions occurred per chance cannot therefore be altogether excluded, elastolytic giant cell granuloma is uncommon and the co-occurence with leprosy in the same cutaneous lesion suggests a more intimate relationship. The two patients presented with different but well-defined forms of leprosy each. This disease is well known for cursing with immunologic abnormalities. Although the underlying ethiopathogenesis of LEGG has not been established and the series presented is small, the detection of LEGG in both patients strongly suggests that the immunologic system does play a role in the pathogenesis of this elastolytic disorder. Inflammatory infiltrates, especially leukocytes and macrophages, are associated with elastase activity.23,24Since inflammatory infiltrate, found in all cases of leprosy, is composed not only by macrophages, but also of substantial numbers of T-lymphocytes with the predominance of the CD8 subset,25 one must question the nature of LEGG. It is therefore reasonable to assume, at least in our cases, that LEGG is not primary at all, but rather it represents an unusual elastolytic disorder that is secondary to an inflammatory process in which immunologic mechanisms are involved. The annular configuration of these lesions thus resulted from elastolytic activity of infiltrating inflammatory cells in the center and peripheral spreading of the active process.
Therefore, other factors such as actinic damage to the skin altered by leprosy, in view of the history of prolonged sun exposure of our two patients, seemed to predispose the dermis to elastic fiber alteration or contribute to the abnormal elastic fiber catabolic processes. Generally speaking, it is unknown whether sunlight and/or any other factors may initiate the essential degeneration of the elastic fibers, which are then recognized as foreign bodies and phagocytized by histiocytes, or if these factors may induce a deviation of the foreign body recognition mechanism and/or an activation of the phagocytosis function of the histiocytes to cause phagocytosis of their own elastic fibers. A photoallergic drug reaction seems improbable, both patients took no drugs, and the pathologic findings do not support this possibility. It remains to be determined whether these observations reflect the altered structure or loss of elastin seen histologically in aging skin. However, we are unable to provide a satisfactory explanation for the etiology of our patient's dermatologic process. The mechanisms that govern this association and whether they are of any biological significance in the pathogenesis of leprosy are uncertain.
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Received in April,
14th of 2000.
Approved by the Consultive Council and accepted for publication in April, 2nd of 2002.
*Work done at "IPAC - Instituto de Patologia Geral e Cutânea".