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.

Antiphospholipid antibodies, antiphospholipid syndrome and infections.

Since the association between antiphospholipid antibodies (aPL) and syphilis was first described, many other viral, bacterial and parasitic infections have been shown to induce antiphospholipid antibodies, notably anticardiolipin antibodies (aCL). A review of the literature shows that while aCL occur frequently in viral infections, particularly in HIV (49.75%), HBV (24%) and HCV (20%), it is very rarely associated with anti-beta2 glycoprotein I antibodies (anti-beta2GPI) and is not correlated with thrombosis risk or hematological manifestations of the antiphospholipid syndrome (APS). Concerning bacterial infections, aCL is often present in leprosy (42.7%), where it is frequently associated with the presence of anti-beta2GPI (44.8%), and in syphilis infections (8 to 67%), though without correlation with thrombotic events. Though few individual patients with unequivocal infection-induced aPL satisfy criteria for APS, the lack of statistical association with thrombotic events strongly argues against the identification of a true APS subset in this context. However, physicians should keep in mind the fact that an infection, generally bacterial, in patients with confirmed APS, may lead to catastrophic antiphospholipid syndrome with a possible fatal outcome.

An adapted ELISA method for differentiating pathogenic from nonpathogenic aPL by a beta 2 glycoprotein I dependency anticardiolipin assay.

With the currently available commercial kits, as well as homemade assays for detecting anticardiolipin antibodies (aCL), it is not possible to discriminate nonpathogenic, beta 2 glycoprotein (GPI)-independent, infection-related antibodies from those of patients with the true autoimmune thrombotic syndrome, known as antiphospholipid syndrome (APS). We devised an assay that is able to differentiate these two types of antibodies by determining the beta 2 GPI requirements to bind in a cardiolipin ELISA. Beta 2 GPI was purified by perchloric acid precipitation, and fixed amounts were used in the dilution solutions of the tested samples that were also tested with no source of beta 2 GPI. The ELISA plates were coated with cardiolipin, as usual, and blocked with a chicken ovalbumin solution. The serum samples had to be highly diluted in order not to have beta 2 GPI from the patient serum. The reaction was detected with alkaline phosphate tablets and developed with pNp in diethanolamine buffer. The adapted ELISA aCL assay described here was able to discriminate infectious [syphilis, hepatitis C virus (HCV), dengue fever, human immunodeficiency virus (HIV) and leprosy] and autoimmune [primary APS and systemic lupus erythematosus (SLE) related APS]. Further testing should be performed to demonstrate that this method consistently differentiates pathogenic antibodies that bind in an aCL ELISA only in the presence of beta 2 GPI.

Distinguishing features of anti-beta2 glycoprotein I antibodies between patients with leprosy and the antiphospholipid syndrome.

Anticardiolipin (ACA), anti-beta2 glycoprotein I (beta2GPI), and antiprothrombin antibodies of IgG and IgM classes were quantitated by enzyme-linked immunosorbent assays in 176 untreated leprosy patients across the histopathological spectrum. Positivity rates ranged from 21% (IgG ACA) to 30% (IgM anti-prothrombin) versus 4% in healthy controls (p <10(-2) to 10(-3)). Levels of IgM anti-beta2GPI and IgG ACA were significantly higher in lepromatous leprosy and multibacillary patient subgroups. IgG3 was the most common subclass reactive to both beta2GPI and prothrombin in selected high-titer leprosy sera, unlike antibodies from patients with the antiphospholipid syndrome (APS) largely restricted to IgG2. In leprosy patients, but not in the APS control group, there was no statistical correlation between ACA and anti-beta2GPI antibody levels. Likewise, a large fraction of anti-beta2GPI positive sera (36/45 and 28/44 for IgG and IgM, respectively) were unreactive in the standard ACA assay. Most assayed anti-beta2GPI antibodies from leprosy patients showed (i) ability to recognize both human and bovine beta2GPI immobilized on non-irradiated polystyrene plates, (ii) concentration-dependent inhibition of binding by cardiolipin, and (iii) relatively high avidity binding to fluid-phase beta2GPI, thereby differing from those found in APS. Finally, the location of the major epitopic region on the beta2GPI molecule targeted by autoantibodies was different in leprosy and APS, as assessed by direct binding to domain I- and V-deleted mutants and competition with the mouse monoclonal antibody 8C3, directed at domain I. Thus, leprosy-related antiphospholipid antibodies comprise persistent IgG and IgM anti-beta2GPI that differ from APS-related ones with respect to IgG subclass, avidity and epitope specificity, possibly reflecting distinct pathophysiological significance.