Lucio-Phänomen

Lucio's phenomenon (LP) occurs in patients with Lucio leprosy (LuL). Some interpret the cutaneous lesions and their histopathology as a thrombotic/occlusive condition, while others consider it leukocytoclastic vasculitis. The clinical similarities between the cutaneous manifestations of LP and antiphospholipid syndrome (APS) led us to investigate the relationship between these two pathological conditions. We studied the clinical, laboratory and histopathologic aspects of LuL and LP in one patient and compare these results to APS. The examination of antiphospholipid antibodies showed positive anticardiolipin (aCL) and lupus anticoagulant (LAC). The histopathological slides of cutaneous biopsies were stained by hematoxylin-eosin and Fite-Faraco. They showed the typical features of LuL, as well as thrombi, endothelial proliferation, vessel wall thickening and obliteration of the lumen. Leukocytoclastic vasculitis was not found. The clinical pattern of LuL in our case is identical to that described by Lucio and Latapi. The necrotic lesions of LP in our patient resembled APS. This suggests that LP could be considered APS secondary to LuL. Multidrug treatment for multibacillary patients (MDT-MP) was successful, with no need for thalidomide or systemic corticosteroids.     

A 75‐year‐old woman with primary antiphospholipid syndrome presenting with livedoid vasculopathy

The clinical presentation of primary antiphospholipid syndrome (PAPS) can vary, often mimicking many other medical conditions. Therefore, it is difficult to diagnose at the first presentation because of the absence of classical symptoms. We described an unusual presentation of PAPS mimicking livedoid vasculopathy (LV), where the only diagnostic clue at the initial presentation was skin lesions in both lower legs. A 75‐year‐old Han Chinese woman presented with features mimicking LV, without clinically significant antiphospholipid syndrome (APS). After many relevant laboratory examinations and histopathological examination, the patient was finally diagnosed as having PAPS. LV should not be treated as an independent disease, but as a skin manifestation. A high degree of suspicion of APS is needed in patients presenting or diagnosed with LV. Early interventions are necessary to prevent and reduce the risk of thrombosis. This case presents a rare clinical manifestation and provides significant information on PAPS.     

Cutaneous papules and nodules in the diagnosis of the antiphospholipid syndrome

Of 11 patients with primary or secondary antiphospholipid syndrome (APS), four exhibited papules or nodules on the finger, sole or leg as the initial cutaneous manifestation. Histological examination demonstrated thrombosed vessels or vessels containing organized thrombi in the dermis or in the subcutaneous fat tissue. Cutaneous papules and nodules should be recognized as skin manifestations of APS. Screening tests for antiphospholipid antibodies and lupus anticoagulant are required in patients with cutaneous papules or nodules of unknown aetiology. In cases of positive antiphospholipid antibodies and/or lupus anticoagulant, histological examination is critical in the establishment of the diagnosis of APS.     

Diffuse leprosy of Lucio and Latapí: a histologic study

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 phenomenon and Lucio leprosy

Lucio phenomenon is a peculiar reactional state associated with Lucio leprosy; both exhibit a restricted global distribution. The exact underlying pathomechanism of Lucio phenomenon, which may be fatal at times, still needs further elaboration. A case of relapse of partially treated nodular lepromatous leprosy presenting with Lucio phenomenon is reported, along with a brief review of the literature.     

Criteria for the diagnosis of antiphospholipid syndrome in patients presenting with dermatologic symptoms

The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the occurrence of arterial and/or venous thromboembolic events and obstetric complications in the setting of circulating antiphospholipid antibodies. Dermatologic manifestations are commonly seen in APS with almost half of the patients exhibiting varied conditions such as ulceration, splinter hemorrhages, and livedo reticularis. In this paper, we report the case of a 12-year-old boy who was diagnosed with APS after presenting with livedo reticularis and positive antiphospholipid antibodies. We discuss the difficulty of diagnosing APS in patients presenting solely with dermatologic complaints, as these skin manifestations are not specific enough for APS to be included in the Sapporo diagnostic criteria. Proposed revisions to the Sapporo criteria to increase its specificity and sensitivity are also addressed.     

抗磷脂综合征的皮肤表现

抗磷脂综合征是一种以反复动静脉形成、流产、血小板减少及血抗磷脂抗体持续阳性为特征的系统性自身免疫性疾病。该综合征可以累及包括皮肤在内的全身任何器官。临床上皮肤表现可作为其首要症状,多见于网状青斑、Sneddon综合征、白色萎缩、皮肤溃疡坏死、斑状萎缩和Degos病等。掌握抗磷脂综合征的皮肤表现对其早期诊断、及时治疗极为关键。     

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.     

Necrotic erythema nodosum reaction associated with histological alterations of Lucio’s phenomenon

Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio’s phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology.     

Lucio's phenomenon: another case reported in Brazil

Lucio's phenomenon is defined as a variant of type 2 leprosy reaction. It is a rare event, occurring in the evolution of leprosy of Lucio and other forms of lepromatous leprosy. It has an exacerbated proliferation of Hansen bacilli in its pathophysiology, which invade blood vessel walls and injure endothelial cells, causing endothelial proliferation and decreasing the vascular lumen. This fact, associated with inflammatory reactions and changes in the coagulation system causes vascular thrombosis, ischemia, infarction and tissue necrosis, leading to the histopathological characteristic of the phenomenon. We report a case of lepromatous leprosy with irregular treatment that developed Lucio's phenomenon. Treatment with multidrug therapy, antibiotics, steroids and thalidomide achieved a favorable outcome.     

Delayed cutaneous reactions to heparin in antiphospholipid syndrome during pregnancy

BACKGROUND: Clinical symptoms related to antiphospholipid antibodies often first occur during pregnancy with the diagnosis of antiphospholipid syndrome (APS). Unfractionated heparin (UFH) and low-dose aspirin are considered as first-line treatments for pregnant women with APS and recurrent fetal loss. However, in addition to an increased incidence of hemorrhagic side-effects and thrombocytopenia there are a number of drug eruptions with cutaneous components secondary to the use of UFH. One of these eruptions has been classified as a delayed type I.V. hypersensitivity reactions at the sites of UFH injections. The majority of these reactions occur in pregnant women. METHOD: We present three pregnant patients who developed delayed hypersensitivity reactions at the sites of UFH injections. Two patients had documented APS and the other patient had two previous spontaneous abortions. RESULTS: The histopathologic and immunohistochemical findings in the biopsy specimens from the sites of the delayed reactions were distinctive. The inflammatory infiltrate contained CD3+ and CD4+ lymphoid cells with plasma cells, and eosinophils. There was a marked increased in mast cells with increased stromal cells within the dermis and increased vascular proliferation. CONCLUSIONS: The distinctive histopathologic and immunohistochemical features seen in the delayed hypersensitivity reactions at the sites of UFH injections may be modulated by the immunomodulatory effects of UFH as well as the hormonal levels and cytokine patterns during pregnancy. Alternative therapies may not always be successful in resolving the reactions.     

Localized cutaneous necrosis associated with the antiphospholipid syndrome

A 34-year-old woman with systemic lupus erythematosus and high titres of antiphospholipid antibodies was admitted to hospital suffering a viral illness but developed haemorrhagic and necrotic areas on the neck and anterior chest 7 days following cessation of warfarin. Anticoagulation had been initiated following a retinal vein thrombosis, but was ceased on day 4 of admission when she was found to be excessively anticoagulated (international normalized ratio (INR) > 10). However, at the time of developing the cutaneous lesions, the INR was sub-therapeutic. Histology of a skin biopsy from the neck revealed thrombosis of upper dermal blood vessels without vasculitis, consistent with antiphospholipid antibody-related skin necrosis. This case illustrates one of the cutaneous features that can occur in patients with elevated titres of antiphospholipid antibodies and the importance of closely monitoring anticoagulation in such patients.     

Bullous systemic lupus erythematosus with antiphospholipid syndrome

We report the case of a 44-year-old male with a 10-year history of manifestations of the rare form of bullous systemic lupus erythematosus (SLE) with coexisting antiphospholipid syndrome (APS) that remained undiagnosed until thrombotic-embolic episodes appeared and high titres of anticardiolipin (ACL) antibodies were detected. The patient fulfilled the criteria for SLE and the atypical cutaneous manifestations together with histopathological changes and a favourable response to sulphones were the grounds for the diagnosis of the bullous variety of SLE. Treatment with prednisolone, acenocoumarol and dapsone resulted in marked clinical improvement, reduction in antinuclear antibodies (ANAs) and normalization of ACL antibody titres.     

Lupus erythematosus with antiphospholipid syndrome and erythema multiforme-like lesions

The occurrence of erythema multiforme (EM) in patients with lupus erythematosus (LE) has been described previously as a coincidental association. In contrast, LE with EM-like lesions and a peculiar immunological pattern, including positive rheumatoid factor, antinuclear antibodies and a serum antibody against an extract of human tissues recently recognized as similar to Ro (SSA), constitutes an established entity named Rowell's syndrome. We describe a woman with LE and long-standing widespread vesiculobullous and necrotic haemorrhagic EM-like lesions in combination with Ro (SSA) and scl-70 antibodies and the typical laboratory findings of the antiphospholipid syndrome (APS), namely lupus anticoagulant, anticardiolipin antibodies and prolonged activated partial thromboplastin time. This case could conceivably be consistent with a diagnosis of Rowell's syndrome, if the latter is regarded as a clinicopathological spectrum. However, the coexistence of LE, persistent EM-like disease and incomplete APS may also fulfil the diagnostic criteria for the 'multiple autoimmune syndromes'. We speculate that the laboratory markers of APS play a pivotal part in such an unusual clinical presentation.     

Two cases of livedo vasculopathy with non‐criteria antiphospholipid antibodies

Livedo vasculopathy is characterized by reticular distribution of purpuric macules and papules of the lower legs, caused by intraluminal thrombosis of small vessels. Antiphospholipid antibodies are detected in a subset of these patients. We treated two cases (a 34‐year‐old man and a 46‐year‐old woman) with livedo vasculopathy. In both cases, thrombosis was seen only in the skin. The presence of immunoglobulin (Ig)G or IgM anticardiolipin antibody (Ab), IgG or IgM anti‐β₂‐glycoprotein I Ab, or lupus anticoagulant are necessary for criteria‐based diagnosis of antiphospholipid syndrome. However, our patients were negative for these Ab, and instead had either IgG antiphosphatidylethanolamine Ab or IgA anticardiolipin Ab. These Ab are suggestive of antiphospholipid syndrome but are not considered “criteria” Ab. This report demonstrates the existence of antiphosphatidylethanolamine Ab or IgA anticardiolipin Ab in patients with livedo vasculopathy. However, the frequency and significance of these Ab in livedo vasculopathy should be confirmed in larger longitudinal studies.     

Immunoglobulin G4-positive multi-organ lymphoproliferative syndrome with antiphospholipid antibody syndrome

We report immunoglobulin (Ig)G4-positive multi-organ lymphoproliferative syndrome (IgG4(+) -MOLPS) with antiphospholipid antibody syndrome (APS) in a 56-year-old Japanese man presenting with purpuric patches on his legs. Skin biopsy revealed leukocytoclastic vasculitis. Laboratory tests demonstrated high levels of serum IgG and IgG4, hypocomplementemia and anticardiolipin antibody. Echography of the lower limbs and pulmonary scintigraphy showed a thrombus in the left soleal vein and multiple emboli in the basal part of both inferior pulmonary arteries. Computed tomography revealed systemic lymphadenopathy. Histologically, there was reactive paracortical hyperplasia with proliferation of histiocytes and infiltration of IgG4-positive plasma cells. We made a diagnosis of IgG4(+) -MOLPS with APS. To our knowledge, this complication has not been reported previously.     

A fatal case of Lucio phenomenon from India

A 65-year-old man presented with cutaneous ulcerations involving the legs, hands, abdomen, buttocks, and pinna, along with fever, arthralgia, and anorexia for the prior 10 days. On cutaneous examination, dark, irregular-shaped bizarre erythematous purpuric spots and angulated ulcers were seen over bilateral, upper extremities and trunk including dorsum of hands, finger tips and the pinnae of both ears. Most striking were the presence of multiple deep ulcers covered with a blackish eschar and in some areas yellow slough eroding the subcutaneous tissue with ragged margins. These ulcers were distributed symmetrically over the thighs, lower legs and gluteal region. Slit-skin smear examination revealed a bacterial index (BI) of 6+ with globi from earlobes, ulcers 3+, eyebrows 3+ and normal skin 2+ and morphologically showed mainly solid (20-30%), fragmented (60-70%) and granular (5-10%) acid-fast bacilli. Biopsy from the ulcer margin revealed an ulcerated epidermis and dermis. The dermis had infiltrate of foamy macrophages, and evidence of ischemic necrotizing vasculitis, with fibrinoid necrosis and new vessel formation. There was presence of clumps of acid-fast bacilli (AFB) within macrophages, periadnexally, perivascularly, and also within endothelial cells. These clinical and histopathological features helped us to arrive at the diagnosis of Lucio phenomenon in an untreated case of Lucio leprosy which is rarely reported from areas other than Mexico.     

Some unusual type 2 reactions in leprosy

Background Type 2 reactions with lepromatous leprosy (LL) not occurring during multi‐drug therapy (MDT) have been reported. Methods Three patients have been described, each representing a prototype, the first presenting as bullous erythema nodosum leprosum (ENL), second with ENL erupting after treatment for co‐existing pulmonary tuberculosis and resembling immune reconstitution inflammatory syndrome, and a third patient with recurrent Sweets‐syndrome like presentation who had taken incomplete MDT in the past for leprosy. In all, the diagnosis was established by demonstration of acid‐fast bacilli (AFB) on slit‐skin smears (SSS) and histopathology. Results & Conclusion The fact that reactions can occur in patients with clinically inapparent LL, who are more likely to present in general hospitals, has been reemphasized to enhance awareness among physicians. First presentation of leprosy as ENL is probably precipitated by common antibiotics taken for other illnesses. Since reactional episodes can occur before, during and after MDT for leprosy and the clinical picture is not specific to any of them, it is important to ascertain the status of anti‐leprosy therapy during these episodes and treat them accordingly.     

Leg ulcers and antiphospholipid antibodies. Prospective study of 48 cases]

BACKGROUND: Leg ulcres can be seen as manifestations of antiphospholipid syndromes but their pathogenic relationship with vascular thrombotic events secondary to antiphospholipid antibodies remains to be defined with precision. A significant association between anticardiolipin antibodies and venous leg ulcers has been described. We conducted this study to determine whether such an association is found in venous ulcers and if it could also be present in cases involving the arterial and/or arteriolar circulation. PATIENTS AND METHODS: From December 1995 to March 1997, 48 patients with leg ulcers involving venous (27 cases), arteriovenous (9 cases) or arteriolar (12 cases) circulations were admitted. The etiologic diagnosis was based on clinical presentation and duplex Doppler findings examining the superficial and deep venous and arterial circuits. Antiphospholipid antibodies were searched for in all cases: VDRL, ELISA for IgG and IgM antiphospholipid antibodies, antiprothrombinase circulating anticoagulant. RESULTS: Circulating anticoagulants were found in 22 of the 48 patients (46%): 12/27 (44%) involved venous leg ulcers (anticardiolipin antibodies, 5 cases; circulating anticoagulants, 4 cases; both, 2 cases); 1/9 involved arteriovenous ulcers (anticardiolipin antibodies, 5 cases); 9/12 involved arteriolar ulcers (anticardiolipin antibodies, 3 cases; circulating anticoagulants, 6 cases; both, 3 cases). Seven of the 9 patients also had severe arteritis. A past history of venous thrombosis was found in 3 cases with venous ulcers and antiphospholipid antibodies. One patient among the 5 with arteriolar ulcers had a past history of arterial thrombosis. DISCUSSION: Our cohort is too small for a formal conclusion but underlines two points: 1. antiphospholipid antibodies can be associated with venous ulcers independently of thrombosis history. The hypothesis that leukocyte stasis and endothelial cell activation causes an immune reaction implicating antiphospholipid antibodies has been put forward. The usefulness of an antiaggregate treatment or an anticoagulant treatment should be discussed, 2. The possible association between arteriolar ulcers and antiphospholipid antibodies requires further large scale studies.     

Leprosy treatment during pregnancy and breastfeeding: A case report and brief review of literature

Leprosy is a chronic disease which primarily affects the skin, mucous membranes and peripheral nerves due to Mycobacterium leprae. It is now infrequent in Europe and is rarely reported during pregnancy. Leprosy can be exacerbated during pregnancy, and without treatment it can permanently damage the skin, nerves, limbs and eyes. Therefore, it is important to treat leprosy during pregnancy. This article describes a patient with multibacillary lepromatous leprosy who was treated with multidrug therapy during pregnancy and breastfeeding. The patient delivered a healthy baby girl without perinatal complications, and the infant's growth and development were normal during the 1‐year follow‐up period. Multidrug therapy consisting of dapsone, rifampicine, and clofazimine is highly effective for people with leprosy and considered safe, both for the mother and the child. Antileprosy drugs are excreted into human milk but there is no report of adverse effects except for skin discoloration of the infant due to clofazimine. Multidrug therapy for leprosy patients should be continued unchanged during pregnancy and breastfeeding.