Synovitis-acne-pustulosis-hyperostosis-osteitis syndrome and psoriatic arthritis exhibit a different immunogenetic profile.

BACKGROUND AND OBJECTIVES: Patients with psoriatic arthritis (PsA) as well as those with synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome share some common features, and in fact, for many authors the SAPHO concept fits well into the broader concept of PsA. However, some clinical features are unique to the SAPHO syndrome, and in the other hand, these patients do not show the known association between the HLA-B27 antigen and the spondyloarthropathies. To date, there are no studies comparing the immunogenetic profile of these two conditions, so the main objective of the present report was to analyse whether or not both entities may share the same genetic basis. PATIENTS AND METHODS: All patients with SAPHO syndrome (n=25) seen in a single university hospital from 1985 to 2005 were recruited and followed up in standardised manner in order to study their main characteristics and HLA profile. The HLA-Cw6, DR and B27 antigen distribution of these cases was compared to that of 50 patients with psoriasis vulgaris, 120 with PsA, and 170 healthy blood donors. PsA patients were classified in accordance with their predominant pattern observed in the last 5 years of disease evolution. Odds ratios (OR) values were calculated to measure the strength of the association between HLA antigens and disease, while the statistical significance of the association was assessed with a two-tailed Fisher's exact test. P<0.05 values were considered significant. RESULTS: No association was found between HLA-Cw6, B27, or DR antigens, and SAPHO syndrome. HLA-Cw6 was strongly associated with psoriasis, OR 12 (95% CI: 5.6-26, p<0.0001) and PsA, OR 10 (95% CI: 5.4-19.5, p<0.0001), however this antigen was equally distributed among the three articular categories of PsA. HLA-DR4 was found under-represented in PsA patients compared to controls, OR 0.4 (95% CI: 0.2-0.7, p=0.002). HLA-DR7 correlated well with psoriatic oligoarthritis, OR 9.6 (95% CI: 2.9-28, p<0.0001), HLA-DR8 was found associated with polyarthritis, OR 6.7 (95% CI: 2-25, p=0.002), while HLA-B27 was over-represented in psoriatic spondylitis, OR 10 (95% CI: 3.3-25, p<0.0001). CONCLUSIONS: Psoriasis/PsA and SAP-HO syndrome show a different immunogenetic background, however the genetic basis of SAPHO syndrome remains unknown.

Radiographic features of hereditary articular chondrocalcinosis. A comparative study with the sporadic type.

To assess the radiological features of hereditary articular chondrocalcinosis, we performed a blind comparative study between 21 randomly selected patients with hereditary disease and 21 cases of sporadic pseudogout matched for age and sex. Each individual had AP projections of the hands, pelvis and knees. The films were evaluated for the presence of articular chondrocalcinosis and for the severity of the associated degenerative arthropathy. A grade of 0 to 3+ was assigned to each of the 4 variables of osteoarthritis: joint space narrowing, sclerosis, osteophytosis and subchondral cysts. The mean number of joints with chondrocalcinosis and its distribution was similar in both groups. In addition, no differences were found in the overall severity of the associated degenerative arthropathy. In both groups the disease was characterized by oligoarticular calcification and a mild degenerative arthropathy. These data along with data from other reported pedigrees, show that the radiological appearance in the hereditary type is frequently indistinguishable from that commonly observed in sporadic articular chondrocalcinosis.

Effects of D-penicillamine on mononuclear cells in vitro.

D-penicillamine (D-pen) inhibited pokeweed mitogen-induced plaque-forming cell (PFC) response in a dose-dependent manner. This inhibition was irreversible as preincubation for a few hours with the drug followed by washes still caused suppression of the PFC response. Pretreatment of the different mononuclear cell populations with D-pen for short periods (2-24 h) showed that both macrophages (Mo) and B lymphocytes were affected by the drug. By contrast T cells were resistant. Mo appears to be more susceptible to D-pen than B cells, and in the case of drug-treated Mo, the response was restored completely with the addition of 20% fresh Mo. Our results show that D-pen, without exogenous Cu2+, inhibits the polyclonal immunoglobulin secretion by human mononuclear cells in vitro due to a strong effect on both Mo and B cells. This may explain the decrease in serum immunoglobulin levels seen in patients with rheumatoid arthritis undergoing this therapy.

Effects of sodium aurothiomalate on the polyclonal immunoglobulin secretion by human mononuclear cells in vitro.

Sodium aurothiomalate (GSTM) inhibited the pokeweed mitogen induced plaque forming cell (PFC) response in a dose dependent manner. This inhibition was irreversible as preincubation for 2 h with the drug followed by washes still caused a suppression of the PFC response. Pretreatment of the different mononuclear cell populations necessary for the PFC response with GSTM for short periods (2-24 h) showed that both macrophages (M phi) and B lymphocytes were inhibited by the drug but that T cells were resistant. In the case of GSTM treated M phi the response was restored partially with exogenous interleukin-1, and completely with the addition of 20% fresh M phi. Our results show that the inhibition of polyclonal immunoglobulin secretion by human mononuclear cells in vitro is due to an effect of GSTM on both M phi and B lymphocytes. This may explain the decrease in serum immunoglobulin levels seen in patients receiving chrysotherapy.

Roentgenographic features of the arthropathy associated with CPPD crystal deposition disease. A comparative study with primary osteoarthritis.

We assessed the radiological features of the arthropathy seen in patients with calcium pyrophosphate dihydrate (CPPD) disease or pseudogout. Standard AP projections of the hands, pelvis and knees were evaluated in 74 patients with pseudogout, 68 cases of primary osteoarthritis (OA) and 78 "normal" controls matched by age and sex. A grade from 0 to 3+ was assigned to each of the 4 variables of OA: joint space narrowing, sclerosis, osteophytosis and subchondral cysts. Radiographic findings of OA were more prevalent (p less than 0.005) and severe (p less than 0.001) in the group with pseudogout than in the controls. When the groups with pseudogout and primary OA were compared, no significant differences were found in the overall severity of radiographic changes with only minor differences in its distribution. The pseudogout patients had greater changes in the metacarpophalangeal joints and a lesser involvement of the trapeziometacarpal joints. No radiological differences were observed in patients meeting McCarty's criteria for clinical types A and C.

Clinical profiles of patients with antibodies to nuclear ribonucleoprotein.

Currently there are no widely accepted criteria for the diagnosis of MCTD. In this work we attempted to define the clinical profile of a group of 68 patients with anti nRNP antibodies, detected by immunoprecipitation in 0.6% agarose. The diagnosis of each collagen vascular disease was established in every patient, who met with the strict diagnostic criteria either at clinical presentation or during the follow-up period. Twenty-eight patients had SLE, 9 had classical erosive RA, three had PSS and one had PM. The only distinctive features in the group of SLE with anti nRNP was an increased incidence of anti Sm antibodies (p less than 0.05). In the RA group there was a trend towards a high frequency of Raynaud's phenomenon and swollen hands. At clinical presentation twenty-seven patients did not fulfil enough criteria to be diagnosed of any of the well-defined collagen vascular disease. They presented an undifferentiated syndrome, characterized clinically by Raynaud's phenomenon (100%), swollen hands (88.9%) and joint symptoms (88.9%), with scarce tendency of developing severe systemic manifestations. The main laboratory abnormalities in this group were hypergammaglobulinemia, mildly increased ESR, abnormal levels of CIC, negative anti nDNA and anti Sm antibodies, and the virtual absence of hypocomplementemia. During a clinical course of 96 +/- 72.5 months only one patient evolved into another collagen disease (SLE). The clinical course in the remaining cases, was stable improving with low doses of prednisone and/or NSAID. We suggest considering this undifferentiated syndrome as a distinct entity, for which the already classical term of MCTD could be reserved.