Prevalence and clinical patterns of psoriatic arthritis in Indian patients with psoriasis.

BACKGROUND: The prevalence and clinical patterns of psoriatic arthritis (PsA) varies in different parts of the world and there is little clinical and epidemiological data from the Indian subcontinent. AIMS: Our study was designed to evaluate the prevalence and clinical patterns of PsA in Indian patients. METHODS: This was a non-interventional, cross-sectional study, in which 1149 consecutive psoriasis patients seen over 1 year were screened for PsA according to classification of psoriatic arthritis (CASPAR) criteria. Demographic and disease parameters were recorded including Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), and number of swollen and tender joints. RESULTS: Among 1149 patients with psoriasis, 100 (8.7%) patients had PsA, of which 83% were newly diagnosed. The most common pattern was symmetrical polyarthritis (58%), followed by spondyloarthropathy 49%, asymmetric oligoarthritis (21%), isolated spondyloarthropathy (5%), predominant distal interphalangeal arthritis (3%), and arthritis mutilans (1%). Enthesitis and dactylitis were present in 67% and 26% of cases, respectively. The mean number of swollen and tender joints were 3.63±3.59 (range, 0-22) and 7.76±6.03 (range, 1-26), respectively. Nail changes were present in 87% of the cases. The median PASI and NAPSI of the subjects with PsA was 3.6 and 20, respectively. There was no significant correlation of number of swollen/tender joints with PASI or NAPSI. CONCLUSION: There is a relatively low prevalence of PsA among Indian psoriasis patients presenting to dermatologists. No correlation was found between the severity of skin and nail involvement and articular disease.

Pituitary-gonadal hormones and interleukin patterns in leprosy.

The functional status of pituitary-gonadal hormones and their relationship to the pattern of inflammatory cytokines in the lepromatous (LL/BL) and tuberculoid (TT/BT) poles of leprosy were investigated. Gonadotropins [luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and C-reactive protein (CRP) concentrations and erythrocyte sedimentation rate (ESR) were significantly higher in LL/BL leprosy patients than in controls and were not different from controls in TT/BT patients. LH and FSH were positively correlated with IL-1beta, IL-6 and TNF-alpha, and CRP concentrations and ESR. Testosterone plasma levels were significantly decreased in LL/BL patients and not different in TT/BT patients compared with controls. In addition, testosterone levels were inversely correlated with IL-6 and TNF-alpha. Prolactin plasma levels of both LL/BL and TT/BT patients were not different when compared with those of controls. There was a significant positive correlation between IL-6 and TNF-alpha plasma levels and ESR and CRP concentrations. IL-1beta was positively correlated with ESR but not with CRP. The significant correlations between gonadotropins and testosterone and cytokines in leprosy patients suggest that cytokines may have a direct influence at testicular level and may be of pathogenetic significance in leprosy and in other inflammatory states involving reproductive dysfunction.

Dos casos de lepra en Valladolid / Two cases of leprosy in Valladolid

La lepra continúa siendo un importante problema de salud en todo el mundo y aunque en nuestro continente no alcanza cifras de endemia, parece existir una tendencia al alza debido al número de casos importados diagnosticados cada año. Se describen 2 casos de lepra lepromatosa diagnosticados en Valladolid en un periodo de 5 meses. El último caso declarado de esta enfermedad en nuestra comunidad data de hace más de 20 años

Leprosy is still a major health problem on a worldwide level, and although it does not reach endemic levels on our continent, it seems that there is an upward trend due to the number of imported cases diagnosed each year. We present two cases of lepromatous leprosy diagnosed in Valladolid within a five-month period. The last reported case of this disease in our community was over 20 years ago

Kikuchi's disease associated with systemic lupus erythematosus.

A 25-year-old multiparous female presented with fever, joint pains, facial rash and lymphadenopathy of three months' duration. Lymph node biopsy revealed a diagnosis of Kikuchi's disease. She fulfilled seven out of the 11 ARA criteria for SLE. The association of Kikuchi's disease and SLE is rare.

Adrenocortical hormones and interleukin patterns in leprosy.

The functional status of adrenocortical hormones and their relationship to the pattern of inflammatory cytokines in the lepromatous and tuberculoid poles of leprosy were investigated. Interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha plasma levels, C-reactive protein (CRP) concentrations and erythrocyte sedimentation rates (ESR) were significantly higher in LL/BL (lepromatous) leprosy patients than in control subjects. There was a significant positive correlation between IL-6 and TNF-alpha plasma levels and ESR and CRP concentrations. IL-1beta was positively correlated with ESR but not with CRP. Both baseline and stimulated adrenocorticotropic hormone and cortisol plasma levels were not different between patients and control subjects. In contrast, adrenal androgen dehydroepiandrosterone sulphate (DHEA-S) plasma levels were significantly lower in leprosy patients than in sex-matched control subjects. There was a significant inverse correlation between DHEA-S and IL-6, TNF-alpha, and CRP concentrations. This finding may be of pathogenetic significance in this disease and in other inflammatory states.

Adrenocortical hormones and interleukin patterns in leprosy

The functional status of adrenocortical hormones and their relationship to the pattern of inflammatory cytokines in the lepromatous and tuberculoid poles of leprosy were investigated. Interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha plasma levels, C-reactive protein (CRP) concentrations and erythrocyte sedimentation rates (ESR) were significantly higher in LL/BL (lepromatous) leprosy patients than in control subjects. There was a significant positive correlation between IL-6 and TNF-alpha plasma levels and ESR and CRP concentrations. IL-1beta was positively correlated with ESR but not with CRP. Both baseline and stimulated adrenocorticotropic hormone and cortisol plasma levels were not different between patients and control subjects. In contrast, adrenal androgen dehydroepiandrosterone sulphate (DHEA-S) plasma levels were significantly lower in leprosy patients than in sex-matched control subjects. There was a significant inverse correlation between DHEA-S and IL-6, TNF-alpha, and CRP concentrations. This finding may be of pathogenetic significance in this disease and in other inflammatory states.

Does pentoxifylline find a place in the armementarium of leprologists in type II reaction?

Alternative therapeutic interventions in Type II lepra reaction are being considered following serious problems associated with the use of steroids and thalidomide. Pentoxifylline (PTX) has been used in Type II reaction with varying degrees of success. The results of a study on the use of this drug in a dose of 1200 mg per day for a period of 2 months in patients with ENL reaction are discussed. Five patients, one of whom was HIV positive--all with severe Type II reaction, were regularly evaluated for regression of inflammatory symptoms and clinical involution of ENL lesions while on PTX therapy and thereafter. It was found that PTX led to a total elimination of systemic symptoms within a week. ENL lesions regressed in two weeks. However, in one patient, lesions recurred after one month of therapy. It appears that PTX is well tolerated and could be used as an additional drug in the armamentarium of leprologists in the management of Type II reaction, especially in HIV co-infection, where long-term steroids are contraindicated. However, further studies to compare the effects of PTX with currently, widely used drugs for the treatment of ENL reaction are necessary.

The Rubino test for leprosy is a beta2-glycoprotein 1-dependent antiphospholipid reaction.

We describe the isolation and identification of three components required for the Rubino reaction (RR), which is the rapid sedimentation of formalinized sheep red-blood cells (SRBC) initiated by serum from leprosy patients with defective Mycobacterium leprae-specific cell immunity. The Rubino reaction factor (RRF) required for this phenomenon, previously identified as an immunoglobulin M (IgM), was purified from leprosy patient serum by adsorption to formalinized SRBC. Purified RRF IgM, when added to formalinized SRBC, did not produce a positive RR. However, when the contact was carried out in the presence of normal human serum (NHS), cells rapidly sedimented. The purified cofactor from NHS contained two components of 70 000 and 50 000 molecular weight (MW), as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The latter was recognized by the RRF IgM on immunoblot and its N-terminal sequence indicated that it was beta2-glycoprotein 1 (beta2-GP1), an anionic phospholipid-binding protein. Methanol-treated formalinized SRBC did not support the RR. Thin-layer chromatography of an extract of membranes indicated that the SRBC ligand was a cell-surface phospholipid. Cardiolipin inhibited the RR. These data demonstrate that the RR involves a trimolecular interaction in which IgM, beta2-GP1 and an SRBC phospholipid participate. By analogy with the antiphospholipid antibodies (anti-PL) that occur in autoimmune processes, serum samples from 29 systemic lupus erythematosus patients with high levels of anticardiolipin antibodies were submitted to the RR. A positive RR was obtained for 45% (13 of 29 patients). These results modify the paradigm of the absolute specificity of the RR for leprosy and demonstrate that RRF IgM is a beta2-GP1-dependent anti-PL.

Anti-neutrophil cytoplasmic autoantibodies in leprosy.

The objective was to evaluate the frequency of cytoplasmic and peripheral antineutrophil cytoplasmic antibodies (ANCA) in patients with leprosy, and to correlate the presence of ANCA with type and disease activity. Consecutive patients with leprosy were assessed clinically, and IgG ANCA were measured by indirect immunofluorescence. The presence of three of the following was used to assess disease activity: reactional state, fever, new cutaneous lesions, erythrocyte sedimentation rate and C-reactive protein. Sixty-four patients were studied and divided according to the Ridley-Jopling classification: of 38 patients with lepromatous leprosy, eight (21%) had perinuclear (p) ANCA and two (6%) had cytoplasmic ANCA. ANCA titres ranged from 1:20 to 1:320. Of six borderline leprosy patients, one (16%) had p-ANCA. All 20 tuberculoid leprosy patients and 65 healthy control subjects had negative ANCA. There was no correlation between ANCA titres and disease activity in positive patients. ANCA, mainly those with a perinuclear pattern, may be present in leprosy, especially in the lepromatous pole. This disease should be added to the spectrum of diseases with ANCA positivity.

Identification of IgM as the leprosy patient serum factor responsible for rapid sedimentation of formolized sheep erythrocytes.

The serum of some leprosy patients with impaired specific cellular immunity for Mycobacterium leprae causes rapid sedimentation of formolized sheep erythrocytes, a phenomenon known as the Rubino reaction. The Rubino factor was precipitated from positive sera by 5% (w/v) polyethylene glycol (PEG), bound to a concanavalin A (ConA)-Sepharose column and eluted with D-mannose, and was also eluted from a Mono Q column, pH 8.0, with 0.4 M NaCl. The Rubino factor was eluted in a volume which coincided with that of human serum IgM from a Sepharose 6 column. IgM was present in the preparation obtained by this sequence of chromatographic procedures. The correspondence of IgM with the Rubino factor was demonstrated by the following data: a) the Rubino factor was adsorbed to rabbit IgG antihuman IgM-agarose and the activity was recovered in the acid eluate of the column; b) the Rubino reaction was inhibited in the presence of rabbit antihuman IgM antibodies. This behavior was not observed when the same procedures were carried out using anti-alpha 2-macroglobulin antibodies as a control. The rapid sedimentation of formolized sheep red cells caused by the serum of lepromatous leprosy patients was not inhibited by phenolic glycolipid-I, suggesting that the IgM responsible for the Rubino reaction is not directed to this antigen which is specific for M. leprae. There was no correlation between the positivity of the Rubino reaction and the increase in total serum IgM levels observed in 42% of the lepromatous patients evaluated. The demonstration that the Rubino factor is an IgM now permits the identification of the epitope recognized by it, and this may be used as a tool to understand the specific cellular immune unresponsiveness which characterizes lepromatous leprosy.

Study of rheumatic manifestations and serologic abnormalities in patients with lepromatous leprosy.

We investigated the rheumatic and laboratory features associated with rheumatic syndromes in 32 patients with lepromatous leprosy. Twenty-seven (84%) developed a broad range of rheumatic manifestations, the most common being the presence of arthritis which was symmetric and polyarticular, resembling rheumatoid arthritis. The laboratory abnormalities included an elevated sedimentation rate in 32 cases (100%), a positive rheumatoid factor in 6 (18.7%), and antinuclear antibodies in one (3.1%). A careful history and the recognition of rheumatic manifestations will help in the identification of this type of leprosy.

SAA amyloid protein levels in amyloid-prone chronic inflammatory disorders. Lack of association with amyloid disease.

Serum amyloid protein A (SAA) levels were evaluated by a sensitive radioimmunoassay technique in leprosy, juvenile rheumatoid arthritis and chronic osteomyelitis. SAA was elevated in all 3 groups of patients. The level in each of the patient groups did not reflect the presence of secondary amyloidosis. Our study suggests that serum SAA protein levels should not be considered a routine diagnostic test in patients with chronic inflammatory diseases prone to the development of amyloid disease.