Giant Arcuate Lupus Vulgaris with Rapid Progression: A Case Report.

Lupus vulgaris is the commonest form of cutaneous tuberculosis. It is a chronic and slowly progressive disease. It can be transmitted either through hematogenous or lymphatic spread but most commonly through contiguous extension.There are many reports on different form of lupus vulgaris but there are only a few reports on large sized lupus vulgaris. Here, we report a case of 75-year-old man with a giant lupus vulgaris rapidly progressing in just two year's duration. Keywords: cutaneous tuberculosis;lupus vulgaris; Nepal.

Tropical and exotic dermatoses and ulcers.

BACKGROUND: Tropical dermatoses and ulcers, although essentially unique to tropical and subtropical areas, are occasionally seen in Australian general practice on returning travellers and migrants from endemic countries. OBJECTIVE: This article will discuss important causes of tropical and exotic ulcers occasionally seen in Australia. DISCUSSION: As tropical ulcers may mimic many other causes of skin ulceration and nodules, a history of recent travel should arouse clinical suspicion. The time frame since exposure to the causative organism is an important feature in the diagnostic process. For example, pyodermas and cutaneous larva migrans present a few days after contact with the causative agents, whereas leishmaniasis, cutaneous tuberculosis, atypical mycobacterial diseases (swimming pool granulomas) and tropical mycosis take weeks to months to appear.

Lupus neonatal, a propósito de un caso / No disponible

El lupus neonatal es una enfermedad de origen autoinmune causada por anticuerpostransplacentarios de tipo La y Ro, que se dirigen y afectan directamente al recién nacido,causando un amplio abanico clínico. Se presenta el caso de un niño de 1 mes de edad conhallazgos clínicos e histológicos característicos del lupus neonatal(AU)

Neonatal lupus is an autoimmune disease caused by transplacental La and Ro antibodiesthat address and affect directly to the newborn, causing diverse clinical manifestations. We presenta one month old infant, with clinical and histological characteristics of lupus disease(AU)

Minocycline-induced lupus in adolescents: clinical implications for physical therapists.

STUDY DESIGN: Resident's case problem. BACKGROUND: In the United States, minocycline is a frequently prescribed medication for the treatment of moderate to severe acne, a common condition in adolescents. The use of minocycline has been associated with severe adverse effects that frequently comprise a musculoskeletal component, including drug-induced lupus. Physical therapists have the responsibility to identify drug reactions that mimic musculoskeletal symptoms. The patient described herein was a 15-year-old adolescent boy who had taken minocycline for 14 days. He was initially treated by his primary physician on the 15th day of minocycline therapy for symptoms of fever, joint swelling, and a rash. The patient presented to a physical therapist on the 22nd day with complaints of severe myalgia, arthralgia, and severely limited mobility secondary to pain. The patient was referred to a pediatric rheumatologist because of the systemic nature and severity of the symptoms. DIAGNOSIS: The patient was subsequently diagnosed as having drug-induced lupus by a pediatric rheumatologist. The patient's myalgia and arthralgia subsided within 6 weeks, but his strength, coordination, and endurance did not reach their prior levels for 3 to 4 months. DISCUSSION: Physical therapists who include a comprehensive pharmacovigilance component in their patient examination may recognize musculoskeletal symptoms that arise from a nonmusculoskeletal origin. Minocycline is commonly prescribed in the United States as an antibiotic and for treatment of acne and rheumatoid arthritis. Therefore, physical therapists should screen for minocycline use when an adolescent patient or a patient with rheumatoid arthritis presents with diffuse musculoskeletal symptoms. An automated medication monitoring system would provide physical therapists with a means of accessing current information on medication use.

Drug-induced lupus associated with synthetic conjugated estrogens.

OBJECTIVE: To report a case of drug-induced lupus (DIL) in a patient taking Cenestin, a combination product of synthetic conjugated estrogens. CASE SUMMARY: A 54-year-old white female presented with a 4 month history of bilateral arm pain that developed and progressively worsened after initiating Cenestin 0.625 mg daily. The patient's symptoms, findings on physical examination (eg, degenerative changes of the acromioclavicular joint), and laboratory test results (eg, antinuclear antibody titer 1-640 [normal <1-40]) were suggestive of DIL. Her symptoms rapidly resolved with discontinuation of Cenestin and promptly resumed with reinitiation of the drug. Laboratory test values also improved significantly with discontinuation of Cenestin. Based on these findings and the Naranjo probability scale score, this reaction was probably associated with Cenestin. DISCUSSION: DIL differs from systemic lupus erythematosus in that it is caused by prolonged exposure at adequate doses to a drug rather than being an autoimmune reaction. The most commonly reported and studied medications are hydralazine, quinidine, and procainamide. Other medications have been associated with DIL; however, data are limited in these reports, especially with estrogen. There have been no previous reports in the literature of synthetic estrogen products associated with DIL. CONCLUSIONS: A diagnosis of DIL can be very challenging to make, especially since there are no clear criteria on which to base it. While estrogen has rarely been reported to be associated with DIL, it may be considered as a possible cause.

Environment versus genetics in autoimmunity: a geneticist's perspective.

Both environmental as well as genetic factors have been documented to contribute to autoimmunity, as is evident from the accompanying articles in this journal. This raises an important question - which of these two elements plays a more important role in the genesis of autoimmunity? This report encapsulates a geneticist's perspective on this interesting question. Though lupus is used as an example in this essay, the proposed model is envisaged to operate in other autoimmune diseases as well.

Heart involvement in systemic lupus erythematosus, anti-phospholipid syndrome and neonatal lupus.

Cardiac involvement is one of the main complications substantially contributing to the morbidity and mortality of patients suffering from systemic autoimmune diseases. All the anatomical heart structures can be affected, and multiple pathogenic mechanisms have been reported. Non-organ-specific autoantibodies have been implicated in immune complex formation and deposition as the initial triggers for inflammatory processes responsible for Libman-Sacks verrucous endocarditis, myocarditis and pericarditis. Anti-phospholipid antibodies have been associated with thrombotic events in coronary arteries, heart valve involvement and intra-myocardial vasculopathy in the context of primary and secondary anti-phospholipid syndrome. Antibodies-SSA/Ro and anti-SSB/La antigens play a major pathogenic role in affecting the heart conduction tissue leading to the electrocardiographic abnormalities of the neonatal lupus syndrome and have been closely associated with endocardial fibroelastosis.

Abnormal costimulatory phenotype and function of dendritic cells before and after the onset of severe murine lupus.

We analyzed the activation and function of dendritic cells (DCs) in the spleens of diseased, lupus-prone NZM2410 and NZB-W/F1 mice and age-matched BALB/c and C57BL/6 control mice. Lupus DCs showed an altered ex vivo costimulatory profile, with a significant increase in the expression of CD40, decreased expression of CD80 and CD54, and normal expression of CD86. DCs from young lupus-prone NZM2410 mice, before the development of the disease, expressed normal levels of CD80 and CD86 but already overexpressed CD40. The increase in CD40-positive cells was specific for DCs and involved the subset of myeloid and CD8alpha+ DCs before disease onset, with a small involvement of plasmacytoid DCs in diseased mice. In vitro data from bone marrow-derived DCs and splenic myeloid DCs suggest that the overexpression of CD40 is not due to a primary alteration of CD40 regulation in DCs but rather to an extrinsic stimulus. Our analyses suggest that the defect of CD80 in NZM2410 and NZB-W/F1 mice, which closely resembles the costimulatory defect found in DCs from humans with systemic lupus erythematosus, is linked to the autoimmune disease. The increase in CD40 may instead participate in disease pathogenesis, being present months before any sign of autoimmunity, and its downregulation should be explored as an alternative to treatment with anti-CD40 ligand in lupus.

Drug-induced lupus.

Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.

Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

Inorganic mercury (iHg) is known to induce autoimmune disease in susceptible rodent strains. Additionally, in inbred strains of mice prone to autoimmune disease, iHg can accelerate and exacerbate disease manifestations. Despite these well-known links between iHg and autoimmunity in animal models, no association between iHg alone and autoimmune disease in humans has been documented. However, it is possible that low-level iHg exposure can interact with disease triggers to enhance disease expression or susceptibility. To address whether exposure to iHg can alter the course of subsequent acquired autoimmune disease, we used a murine model of acquired autoimmunity, lupus-like chronic graft-versus-host disease (GVHD), in which autoimmunity is induced using normal, nonautoimmune prone donor and F1 recipient mice resistant to Hg-induced autoimmunity. Our results indicate that a 2-week exposure to low-dose iHg (20 or 200 micro g/kg every other day) to donor and host mice ending 1 week before GVHD induction can significantly worsen parameters of disease severity, resulting in premature mortality. iHg pretreatment clearly worsened chronic lupus-like disease, rather than GVHD worsening iHg immunotoxicity. These results are consistent with the hypothesis that low-level, nontoxic iHg preexposure may interact with other risk factors, genetic or acquired, to promote subsequent autoimmune disease development.

Cutaneous tuberculosis: diagnosis and treatment.

As we move into the 21st century, cutaneous tuberculosis has re-emerged in areas with a high incidence of HIV infection and multi-drug resistant pulmonary tuberculosis. Mycobacterium tuberculosis, Mycobacterium bovis, and the BCG vaccine cause tuberculosis involving the skin. True cutaneous tuberculosis lesions can be acquired either exogenously or endogenously, show a wide spectrum of morphology and M. tuberculosis can be diagnosed by acid-fast bacilli (AFB) stains, culture or polymerase chain reaction (PCR). These lesions include tuberculous chancre, tuberculosis verrucosa cutis, lupus vulgaris, scrofuloderma, orificial tuberculosis, miliary tuberculosis, metastatic tuberculosis abscess and most cases of papulonecrotic tuberculid. The tuberculids, like cutaneous tuberculosis, show a wide spectrum of morphology but M. tuberculosis is not identified by AFB stains, culture or PCR. These lesions include lichen scrofulosorum, nodular tuberculid, most cases of nodular granulomatous phlebitis, most cases of erythema induratum of Bazin and some cases of papulonecrotic tuberculid. Diagnosis of cutaneous tuberculosis is challenging and requires the correlation of clinical findings with diagnostic testing; in addition to traditional AFB smears and cultures, there has been increased utilization of PCR because of its rapidity, sensitivity and specificity. Since most cases of cutaneous tuberculosis are a manifestation of systemic involvement, and the bacillary load in cutaneous tuberculosis is usually less than in pulmonary tuberculosis, treatment regimens are similar to that of tuberculosis in general. In the immunocompromised, such as an HIV infected patient with disseminated miliary tuberculosis, rapid diagnosis and prompt initiation of treatment are paramount. Unfortunately, despite even the most aggressive efforts, the prognosis in these individuals is poor when multi-drug resistant mycobacterium are present. An increased awareness of the re-emergence of cutaneous tuberculosis will allow for the proper diagnosis and management of this increasingly common skin disorder.

Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions.

Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sjögren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia.

Minocycline-induced clinical and biological lupus-like disease.

A 14-year-old girl developed maculopapular rash, myalgias, arthralgias and myocarditis with elevated anti-nuclear and anti-double-stranded DNA antibodies. She was taking minocycline for acne and all symptoms resolved when this treatment was stopped. The patient has no evidence of disease one year after onset of symptoms. Clinicians should be aware of minocycline's responsibility in inducing lupus-like disease.

Síndrome do lúpus neonatal / Neonatal lupus syndrome

A síndrome do lúpus neonatal (LN) é uma entidade rara, caracterizada por bloqueio cardíaco congênito (BCC)e/ou lesões cutâneas e, eventualmente, associada a alterações hematológicas e hepáticas. Essa síndrome está estritamente relacionada com a passagem transplacentária de auto-anticorpos maternos, particularmente anti-Ro/SSa e anti-La/SSB, sendo considerada um modelo de auto imunidade adquirida passivamente. Aproximadamente, metade das mães são assintomáticas e o restante apresenta síndrome de Sjögren, lúpus eritematoso sistêmico e outras doenças do sistema conectivo. Essa síndrome é a principal causa de bloqueio cardíaco congênito isolado e determina alto índice de mortalidade. Não existe tratamento preventivo para a síndrome, sendo recomendado que a gestação de mães com anticorpos anti-Ro/SSA ou anti-La/SSB tenha acompanhamento de frequência cardíaca fetal rigoroso. Nos casos em que há evidências de inflamação do miocárdio concomitante está indicado o tratamento com corticóide sistêmico que não seja inativado pela placenta, na tentativa de reverter o quadro

Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice.

Mononuclear cell infiltration in glomeruli and renal interstitium is a prominent feature of some types of glomerulonephritis, including lupus nephritis. The mechanism(s) underlying monocyte influx into the kidney is not fully understood. Recently, monocyte chemoattractant protein-1 (MCP-1) has been identified as a chemotactic factor involved in the recruitment of monocytes/macrophages in the glomeruli of rats with mesangioproliferative as well as anti-glomerular basement membrane glomerulonephritis. In the study presented here, renal MCP-1 mRNA expression in New Zealand Black x New Zealand White (NZB/W) F1 mice, a model of genetically determined immune complex disease that mimics systemic lupus in humans, was investigated. Northern blot analysis revealed a single 0.7 kb MCP-1 transcript of very low intensity in kidneys from 2-month-old NZB/W mice that had not yet developed proteinuria nor renal damage. Message levels, which increased markedly with the progression of nephritis and in association with mononuclear cell infiltration, were 10- and 15- fold higher in 8-10-month-old mice than in 2-month-old mice. By in situ hybridization, increased expression of MCP-1 mRNA was demonstrated in glomeruli and, even more striking, in tubular epithelial cells. Western blot analysis demonstrated increased expression of MCP-1 protein in kidneys of 10-month-old NZB/W mice, consistent with MCP-1 mRNA data. When NZB/W mice were treated with cyclophosphamide up to 12 months of age, expression of MCP-1 in the renal tissue remained low, the influx of inflammatory cells did not appear, and glomerular and tubular structures remained well preserved. These data suggest that elevated MCP-1 might act as a signal for inflammatory cells to infiltrate the kidney in lupus nephritis.

Neonatal lupus.

Neonatal lupus, albeit rare, affords an excellent opportunity to examine a disease from bedside to bench. Over the past year there have been numerous publications covering clinical aspects and basic research. The timing of heart block is not random; bradycardia is most often identified between 16 and 24 weeks of gestation. Investigations have focused on this apparently vulnerable period and examined the expression of known (SSA/Ro-SSB/La), novel (p57, endogenous retrovirus-3), and cross-reactive (laminin) autoantigens in fetal hearts of varied ages and in adult hearts. Clinical studies are accumulating, but a unique maternal autoantibody profile is yet to be identified. Anti-52-kD responses, measured by enzyme-linked immunosorbent assay and immunoblot, continue to be a nearly universal finding in mothers whose children have neonatal lupus. The presence of anti-U1RNP in the absence of anti-SSA/Ro-SSB/La antibodies occurs only in cases of isolated cutaneous disease and not (to date) in mothers of infants with cardiac manifestations. Immunogenetically, mothers with affected children appear to be more closely related to Sjögren's syndrome than systemic lupus erythematosus. Asymptomatic mothers do not invariably become ill, and if an asymptomatic mother does develop lupus it is not likely to be life threatening. Heart block is associated with substantial morbidity and mortality. Although treatment of affected fetuses with dexamethasone has successfully diminished associated effusions, this therapy has not reversed established third-degree block. Treatment with sympathomimetics may be beneficial in fetuses with hydropic changes. Prophylactic therapies, other than serial echocardiographic evaluation, are not supported by any published data. To further efforts at both the bench and bedside, research registries were recently established in the United States and Canada.