Diffuse Lepromatous Leprosy Research Articles

Lucio’s leprosy: A clinical and therapeutic challenge

Leprosy has been a challenge in different areas of medicine; in underdeveloped countries it remains a public health problem, in which the social and economic problems facilitate the disease persistence. The diagnosis and consequently the treatment are delayed due to the clinical polymorphism of leprosy, which especially at the beginning the manifestations are not as evident, as is the case of diffuse lepromatous leprosy. This favors the disabilities and the development of the reaction episodes. Fortunately, reaction episodes have decreased with the use of multidrug therapy, and better control of the type 2 reactions has been managed with the use of thalidomide, as in Lucio’s phenomenon.

Lucio Leprosy with Lucio’s phenomenon, digital gangrene and anticardiolipin antibodies

Lucio's phenomenon (LPh) is considered a necrotizing panvasculitis and a variant of leprosy Type 2 reaction, clinically characterised by necrotic-haemorrhagic lesions on the extremities and trunk. LPh is observed in diffuse lepromatous leprosy (DLL or Lucio-Latapí leprosy). This is a distinct form of lepromatous leprosy (LL) reported mainly in Mexico. Anti-phospholipid antibody syndrome (APS) has been rarely described in LPh. We report a case of Lucio-Latapí leprosy with LPh observed in a patient from the province of El Oro in Ecuador, who presented clinical manifestations of long standing DLL (non-nodular infiltration of the skin, collapse of the nasal pyramid, madarosis, atrophy of the earlobes), of LPh (necrotic-haemorrhagic macules with irregular shapes) and of APS (necrosis of the right big and second toe). Histopathology showed perineural and periadnexal foamy macrophages with numerous bacilli (diagnostic of LL) in the subcutis, a mild lobular panniculitis with a large subcutaneous vessel infiltrated by macrophages in the wall (typical of LPh) and vessels of the superficial and mid dermis occluded by thrombi but without signs of vasculitis (typical of occlusive vasculopathy as in APS). Our observations suggest that some cases of LPh may be associated with APS. Anti-cardiolipin antibodies (aCL) and lupus anticoagulant (LA) should be tested in patients with LPh because this may have therapeutic implications.

Lucio’s phenomenon: report of five cases

The different clinical forms of leprosy are mainly related to the variety of immunological responses to the infection. Several forms of lepromatous leprosy are recognized, including macular, nodular, and diffuse. Lucio's phenomenon is a rare but distinctive skin eruption seen in patients with diffuse lepromatous leprosy. The diffuse lesions of Lucio's phenomenon have a predilection for the extremities, can include nodules, and heal with atrophic stellate scars; histologically, a necrotizing vasculitis accompanied by a nonspecific inflammatory reaction may be seen. Because of its rarity and similarity with some manifestations of the rheumatic disease and other causes of vasculitis, Lucio's phenomenon may not be easily recognized, especially in non-endemic countries, which leads to confusing diagnosis and loss of time for treatment. We report five patients with vasculitis caused by Lucio's phenomenon.

The leprosy agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico

Mycobacterium leprae was the only known cause of leprosy until 2008, when a new species, named Mycobacterium lepromatosis, was found to cause diffuse lepromatous leprosy (DLL), a unique form of leprosy endemic in Mexico. We sought to differentiate the leprosy agents among 120 Mexican patients with various clinical forms of leprosy and to compare their relative prevalences and disease features. Archived skin biopsy specimens from these patients were tested for both M. leprae and M. lepromatosis using polymerase chain reaction-based species-specific assays. Etiologic species were confirmed in 87 (72.5%) patients, of whom 55 were infected with M. lepromatosis, 18 with M. leprae, and 14 with both organisms. The endemic regions of each agent differed but overlapped. Patients with M. lepromatosis were younger and were distributed across more states; their clinical diagnoses included DLL (n = 13), lepromatous leprosy (LL) (n = 34), and eight other forms of leprosy. By contrast, the diagnoses of patients with M. leprae did not include DLL but did include LL (n = 15) and three other forms of leprosy. Thus, M. lepromatosis caused DLL specifically (P = 0.023). Patients with M. lepromatosis also showed more variable skin lesions; the extremities were the most common sites of biopsy in these patients. Finally, patients with dual infections manifested all clinical forms and accounted for 16.1% of all species-confirmed cases. Mycobacterium lepromatosis is another cause of leprosy and is probably more prevalent than M. leprae in Mexico. It mainly causes LL and also specifically DLL. Dual infections caused by both species may occur in endemic areas.

Case of Diffuse Lepromatous Leprosy Associated with “Mycobacterium lepromatosis”

An 86-year-old female patient from northeast Mexico presented with diffuse lepromatous leprosy (DLL). Sequence analysis of four genes (rrs, rpoB, sigA, and hsp65) from the skin biopsy specimen identified "Mycobacterium lepromatosis." This is the first independent confirmation of a case of DLL due to M. lepromatosis.

What is the evidence that the putative Mycobacterium lepromatosis species causes diffuse lepromatous leprosy?

Han et al. have made a retrospective isolation of DNA from two patients with fatal Lucio's phenomenon. This DNA does have some molecular differences to M. leprae and may constitute a variant of M. leprae. However the experiments and data needed to confirm that this is a new leprosy-causing species have not yet been done. We have outlined the work that does need to be done. For the moment the assertion that 'M. lepromatosis' is a new leprosy-causing species is not proven.

Autochthonous leprosy in metropolitan France presenting with a diffuse infiltration of the face and febrile illness

Leprosy is now considered in Western Europe as a strictly imported disease. A case of presumed locally acquired diffuse lepromatous leprosy was observed in a native-Portuguese woman living in France who developed an acute febrile presentation with extensive cutaneous signs.

Lucio's Phenomenon Is a Necrotizing Panvasculitis: Mostly a Medium-Sized Granulomatous Arteritis

Lucio's phenomenon (LPh) is a vasculitis clinically described in 1852 and microscopically documented in 1948 in patients with diffuse lepromatous leprosy; however, at present, there is no a clear concept about the pathogenesis of the necrosis, or about the type, size, and site of the damaged vessel. The objective of this study was to elucidate the type, size, site, and form of vessel damage in LPh in a retrospective, clinical, and histopathological study. Clinical information was obtained from the charts and records and/or from the histopathology request. Slides stained with hematoxylin and eosin, Ziehl-Neelsen, and Fite-Faraco were retrieved from our files. Direct immunofluorescence had been performed in 6 cases. Twelve cases fulfilled clinical evidence to make unequivocal diagnosis of diffuse lepromatous leprosy with LPh. All of them had necrotic, irregular, purpuric, and/or ulcerative lesions, which under the microscope showed medium-sized arteries, with their walls involved by clusters of macrophages containing large amounts of bacilli, distortion of the structure of the vessel wall, narrowing, and obliteration of their lumen. Smaller vessels showed changes of the leukocytoclastic type. LPh is a distinctive type of granulomatous and necrotizing panvasculitis; the involved vessels are mostly medium-sized arteries, located deeply in the skin, at the base, and within the hypodermis, but any other vessel is likewise involved, their occlusion leads to ischemic necrosis of the whole skin, frequently with detachment of the epidermis. These changes explain clearly and logically the clinical features observed more than 150 years ago.

A NewMycobacteriumSpecies Causing Diffuse Lepromatous Leprosy

Mycobacterium leprae causes leprosy. M leprae strains collected worldwide have been genetically clonal, which poorly explains the varying severity and clinical features of the disease. We discovered a new Mycobacterium species from 2 patients who died of diffuse lepromatous leprosy (DLL). The Mycobacterium was purified from heavily infected, freshly frozen autopsy liver tissue followed by DNA extraction in 1 case. Paraffin-embedded skin tissue was used for DNA extraction in another case. Six genes of the organism were amplified by polymerase chain reaction, sequenced on cloning or from amplicons, and analyzed. Significant genetic differences with M leprae were found, including a 2.1% divergence of the 16S ribosomal RNA (rRNA) gene, a highly conserved marker of bacterial evolution, and 6% to 14% mismatches among 5 less conserved genes. Phylogenetic analyses of the genes of 16S rRNA, rpoB, and hsp65 indicated that the 2 most related organisms evolved from a common ancestor that had branched from other mycobacteria. These results and the unique clinicopathologic features of DLL led us to propose Mycobacterium lepromatosis sp nov. This species may account for some of the clinical and geographic variability of leprosy. This finding may have implications for the research and diagnosis of leprosy.

Diffuse leprosy of Lucio and Latapí: a histologic study

Ladislao de la Pascua described the spotted or lazarine leprosy for first time in 1844. Later on, Lucio and Alvarado studied and published it with the same names in 1852. Latapí re-discovered it in 1938 and reported it as 'Spotted' leprosy of Lucio in 1948. Frenken named it diffuse leprosy of Lucio and Latapí in 1963. Latapí and Chévez-Zamora explained that the fundamental condition of this variety of leprosy was a diffuse generalised cutaneous infiltration, naming it pure and primitive diffuse lepromatosis, upon which necrotising lesions develop, calling these lesions Fenómeno de Lucio or erythema necrotisans. A great number of histopathological reports have addressed the study of Lucio's phenomenon, and few about the histologic changes that take place in the course of diffuse lepromatous leprosy. The purpose of this work is to report the histologic findings observed in the study of 170 cutaneous biopsies of diffuse leprosy of Lucio and Latapí and 30 of Lucio's phenomenon. This is a retrospective study, which included the examination of 200 biopsy skin specimens from 199 patients with diffuse leprosy at different course of the disease. These cases were diagnosed in Mexico from 1970 to 2004. The histologic examination revealed a vascular pattern affecting all cutaneous vessels, characterised by five outstanding features: a) colonisation of endothelial cells by acid-fast bacilli, b) endothelial proliferation and marked thickening of vessel walls to the point of obliteration, c) angiogenesis, d) vascular ectasia, and e) thrombosis. Necrotising lesions seen in diffuse lepromatous leprosy displayed two histopathological patterns: one of them, non-inflammatory occlusive vasculopathy and, the other one, occlusive vasculopathy, leukocytoclastic vasculitis, large neutrophilic infiltrate and lobular panniculitis. The first appeared as a result of the course of the occlusive vasculopathy produced by the colonisation of endothelial cells by Mycobacterium leprae. The second, as a result of a previous occlusive vasculopathy plus a leprosy reaction which is considered here as variant of ENL. Endothelial cell injury appears to be the main event in the pathogenesis of diffuse leprosy of Lucio and Latapí. Once M. leprae has entered the endothelial cell, the micro-organism damages the blood vessels, leading to the specific changes seen in this variety of lepromatous leprosy.

Lucio's phenomenon/erythema necroticans

Lucio's phenomenon/erythema necroticans is a peculiar reaction pattern that occurs in untreated pure primitive diffuse lepromatous leprosy (PPDL) and/or relapsing leprosy recognized as spotted leprosy of Lucio. The small number of reported cases in the world literature suggests that it is fairly uncommon. Its clinical features are fairly characteristic and consist of extensive, bizarre, painful ulcerations of the skin, with constitutional symptoms being conspicuous by their absence. The clinical diagnosis is confirmed by microscopic pathology marked by proliferation and mobilization of polyblasts and histiocytes, dilatation, endothelial proliferation, luminal occlusion, and thrombosis of the superficial and mid-dermal blood vessels and demonstration of acid-fast bacilli in the blood vessel walls. Its precise pathogenesis is still unclear, but is believed to occur either through the usual or the alternate pathway of complement activation in the natural history of erythema nodosum leprosum. The clinical and immunological features of reactions in leprosy, including erythema nodosum leprosum, are well known and have been critically evaluated elsewhere.

Intra-Articular Osteoid Osteoma at the Elbow: Report of a Case and Review of the Literature

Osteoid osteoma is a benign tumor that may occur in almost any part of any bone. Diagnosis can be difficult, particularly when it is intra-articular. In these cases, osteoid osteoma may present initially with symptoms suggestive of inflammatory arthritis, degenerative joint disease, neoplasm, or infection. We report a case of intra-articular osteoid osteoma in a teenager who presented with a monoarthritis of the elbow. The patient did not have a typical pattern of pain, did not have the typical relief with anti-inflammatory agents, and misinterpretation of the radiographs led to a delay in the diagnosis and definitive treatment. Surgical excision confirmed the diagnosis and resulted in resolution of the monoarthritis. Intra-articular osteoid osteoma must be taken into account in cases of unexplained chronic monoarthritis, with a sterile and relatively noninflammatory synovial fluid. A definitive diagnosis depends on surgical excision and histologic confirmation. Ahigh index of suspicion is necessary to make the diagnosis.

Lucio's Phenomenon and Diffuse Nonnodular Lepromatous Leprosy

The records of ten patients with Lucio's phenomenon showed clinical and histopathological changes similar to those described by others. Lucio's phenomenon is a syndrome distinct from erythema nodosum leprosum as indicated by an absence of fever, leukocytosis and tenderness, a failure to respond to thalidomide, and a restriction to patients with diffuse nonnodular lepromatous leprosy. Lymphopenia associated with splenomegaly in three patients and glomerulonephritis in one patient were unexpected findings of unknown relevance.

Lucio's phenomenon: An immune complex deposition syndrome in lepromatous leprosy

Lucio's phenomenon is an acute lepra reaction in diffuse lepromatous leprosy characterized by cutaneous infarctions secondary to a necrotizing vasculitis. Five cases of Lucio's phenomenon were studied to elucidate the pathogenesis of this complication of leprosy. Direct immunofluorescent studies of the lesions revealed the presence of deposits of complement and immunoglobulin in the walls of dermal blood vessels and in perivascular areas. The deposits were eluted when the cryostat sections of skin were incubated with an acidic buffer. Cryoglobulins of the “mixed type” containing IgG, IgM, IgA, C3, and C1q were found in the serum of four patients. Analysis of the cryoglobulins revealed an enrichment of rheumatoid factor activity in the cryoprecipitate over that of the serum. Immune complexes were found in the serum of all patients. Hypocomplementemia was observed in one patient. These data suggest that Lucio's phenomenon is mediated by the deposition of immune complexes in dermal blood vessels.

Apparently Normal Skin in Lepromatous Leprosy

Biopsy specimens of apparently uninvolved skin from 34 patients with lepromatous leprosy were studied histologically. Bacilli were found in 30 of 31 specimens from clinically polar or near-polar lepromatous patients but not in the three from nonpolar patients. A predominantly perivascular distribution of infiltrate and bacilli is consistent with a hematogenous spread of infection. Subclinical, diffuse lepromatous leprosy is found in patients with nodular lesions and may precede the development of nodules. Study of apparently uninvolved skin may be helpful in classifying patients, in interpreting immunologic responses, and in elucidating the natural history of the illness.

The Lepra Reaction With Necrotizing Skin Lesions

The primary diffuse (the pure and primitive) lepromatous leprosy is a subtype of lepromatous leprosy. Necrotic skin lesions appear rarely in lepra reactions. They are characteristic of the Lucio phenomenon which occurs in patients with diffuse lepromatous leprosy but may be seen in patients who have a severe attack of erythema nodosum leprosum or its variants, erythema multiforme leprosum and an eruption which resembles the allergic vasculitis of Ruiter. Six cases of lepra reaction with necrotizing skin lesions are reported and their clinical features are emphasized.