Thomas T. Provost

Autoimmune-Associated Congenital Heart Block: Demographics, Mortality, Morbidity and Recurrence Rates Obtained From a National Neonatal Lupus Registry

OBJECTIVES The present study describes the demographics, mortality, morbidity and recurrence rates of autoimmune-associated congenital heart block (CHB) using information from the Research Registry for Neonatal Lupus. BACKGROUND Isolated CHB detected at or before birth is strongly associated with maternal autoantibodies to 48-kD SSB/La, 52-kD SSA/Ro and 60-kD SSA/Ro ribonucleoproteins and is a permanent manifestation of the neonatal lupus syndromes (NLS). Available data are limited by the rarity of the disease. RESULTS The cohort includes 105 mothers whose sera contain anti-SSA/Ro or anti-SSB/La antibodies, or both, and their 113 infants diagnosed with CHB between 1970 and 1997 (56 boys, 57 girls). Of 87 pregnancies in which sufficient medical records were available, bradyarrhythmia confirmed to be CHB was initially detected before 30 weeks of gestation in 71 (82%) (median time 23 weeks). There were no cases in which major congenital cardiac anatomic defects were considered causal for the development of CHB; in 14 there were minor abnormalities. Twenty-two (19%) of the 113 children died, 16 (73%) within 3 months after birth. Cumulative probability of 3-year survival was 79%. Sixty-seven (63%) of 107 live-born children required pacemakers: 35 within 9 days of life, 15 within 1 year, and 17 after 1 year. Forty-nine of the mothers had subsequent pregnancies: 8 (16%) had another infant with CHB and 3 (6%) had a child with an isolated rash consistent with NLS. CONCLUSIONS Data from this large series substantiate that autoantibody-associated CHB is not coincident with major structural abnormalities, is most often identified in the late second trimester, carries a substantial mortality in the neonatal period and frequently requires pacing. The recurrence rate of CHB is at least two- to three-fold higher than the rate for a mother with anti-SSA/Ro-SSB/La antibodies who never had an affected child, supporting close echocardiographic monitoring in all subsequent pregnancies, with heightened surveillance between 18 and 24 weeks of gestation.

Systemic lupus erythematosus: a review of clinico-laboratory features and immunogenetic markers in 150 patients with emphasis on demographic subsets.

Clinical and laboratory features as well as immunogenetic markers were analyzed in 150 patients with SLE to determine if demographic factors--age at diagnosis, sex and race--influenced the expression of disease. The overall series included 103 white females, 35 black females, 10 white males and 2 black males; the mean age at diagnosis was 32.5 years. Males had a significantly older mean age at diagnosis than females (40.4 versus 31.8 years) and a significantly higher frequency of peripheral neuropathy (50% versus 18.8%). No other differences in clinical or laboratory features or HLA-DR or DQ phenotype frequencies were noted. Blacks had a significant younger mean age at diagnosis than whites (26.9 versus 33.4 years) as well as significantly higher frequencies of nephritis, hypertension, acute lupus pneumonitis, discoid rash, hyperglobulinemia and hypocomplementemia. There were no differences in autoantibody frequencies between race-specific subgroups. HLA-DR2, DRw52 and DQ1 were significantly associated with SLE in whites compared to controls; no HLA-DR or DQ associations were found with SLE in blacks. In whites, HLA-DR2 was associated with the presence of anti-Ro(SS-A) antibody while HLA-DR3 was associated with the presence of both anti-Ro(SS-A) and anti-La(SS-B) antibody. In blacks, HLA-DR2 was associated with the presence of anti-nDNA antibody. In whites, patients with late-onset SLE (age at diagnosis greater than or equal to 50 years) had significantly lower frequencies of nephritis and mesenteric vasculitis but, on the other hand, a higher frequency of secondary Sjögren syndrome than patients with age at diagnosis less than or equal to 22 years. Similar findings were noted when blacks aged 35 and above were compared to those aged 17 and below at diagnosis. In whites, the frequency of both anti-Ro(SS-A) and La(SS-B) antibodies increased with increasing age as did that of HLA-DR3; HLA-DR2, however, was more frequent in those with younger age at diagnosis. These data suggest the existence of two serologic-genetic subsets of SLE with different age at diagnosis.

Sjögren's Syndrome: Association of Anti-Ro(SS-A) Antibodies with Vasculitis, Hematologic Abnormalities, and Serologic Hyperreactivity

The clinical significance of autoantibodies to Ro(SS-A) and La(SS-B) in Sjögrens syndrome was examined in a retrospective evaluation of 75 patients with symptoms of the sicca complex who had either primary Sjögrens syndrome or Sjögrens syndrome associated with another connective tissue disease. The clinical, hematologic, and serologic features associated with autoantibodies to the small molecular weight ribonucleoproteins Ro(SS-A) and La(SS-B) were ascertained. A striking clinical association of anti-Ro(SS-A) antibodies (found in 33 patients) with extraglandular disease (vasculitis, purpura, and lymphadenopathy) was seen. Hematologic abnormalities (anemia, leukopenia, and thrombocytopenia) were also associated with the presence of anti-Ro(SS-A) antibodies. Furthermore, anti-Ro(SS-A) antibody was associated with hyperglobulinemia, increased serologic reactivity in terms of rheumatoid and antinuclear factors, cryoglobulinemia, and hypocomplementemia. The presence of anti-Ro(SS-A) antibodies defines a subset of patients with Sjögrens syndrome who have systemic clinical manifestations including vasculitis, hematologic abnormalities, and serologic hyperreactivity.

Primary Sjögren's Syndrome with Central Nervous System Disease Mimicking Multiple Sclerosis

Central nervous system involvement has occurred in approximately 20% of patients with primary Sjögrens syndrome evaluated at our institution. Characteristically, the neurologic dysfunction is multifocal, involving both the brain and spinal cord, and is recurrent over time. We present the features of 20 patients with primary Sjögrens syndrome and central nervous system involvement whose neurologic findings, evoked potential abnormalities, and cerebrospinal fluid profiles (elevated IgG indices, oligoclonal bands on agarose gel electrophoresis, and mild pleocytosis with reactive lymphoid cells) closely resembled those of multiple sclerosis. In fact, multiple sclerosis was considered the most likely diagnosis in each of these patients before diagnosis of Sjögrens syndrome, and each patient met criteria for definite multiple sclerosis. The clinical effects of corticosteroid treatment during episodes of acute neurologic dysfunction appeared to be beneficial in these patients.

Bullous Pemphigoid: Clinical and Immunologic Follow-up After Successful Therapy

Thirty-six patients with bullous pemphigoid (BP) have been periodically evaluated for four years. This study demonstrates that BP may occur in a transient predominantly localized form that remits spontaneously, and most BP patients after successful therapy remain in prolonged clinical remission. In this study, all patients with active or recurrent disease had IgG and/or C3 basement membrane zone (BMZ) deposition. Serum anti-BMZ antibodies was an inconstant feature. In most instances, clinical remission of BP was associated with disappearance of BMZ ig and C3 deposition and serum BMZ antibodies. Fluorescein-conjugated, antihuman C3 appears to be a more sensitive immunoreagent than antihuman, class specific, immunoglobulin antisera in detecting positive BMZ staining in BP. Combined therapy with azathioprine plus prednisone appears to be superior to prednisone alone in the treatment of BP.

Sjögren syndrome Central nervous system manifestations

we studied eight patients who had primary Sjogren syndrome and central nervous system (CNS) disorders that were not attributable to other causes. Focal cerebral deficits were observed in five patients. Aseptic meningoencephalitis was seen in five patients, recurrent in one. Spinal cord manifestations in three patients took several forms: acute transverse myelitis, chronic progressive myelopathy, and spinal subarachnoid hemorrhage. Precipitating antibodies to the Ro(SSA) cytoplasmic antigen were detected in the sera of seven of eight patients. This may be relevant to the pathogenesis of CNS disease in Sjogren syndrome, because there is a strong correlation between vasculitis and the presence of anti-Ro(SSA) antibodies in this connective tissue disorder.

Neurologic Complications of Primary Sj??gren??s Syndrome

Although peripheral nervous system disease has been well documented in Sjögrens syndrome (SS), central nervous system (CNS) involvement is considered distinctly uncommon. Sixteen patients with primary SS and CNS disorders not attributable to other causes were the subjects of this study. Cerebral manifestations, both focal and diffuse, as well as spinal cord disease, were observed. Peripheral vasculitis occurred in 12 patients (75%), 83% of whom had anti-Ro(SSA) antibodies. The high proportion of patients with concomitant peripheral vasculitis, and the observed association with antibodies to the Ro(SSA) antigen system which, in other studies, has been linked to vasculitis in SS, suggest that an immune vasculopathy may play a role in the pathogenesis of the CNS disease of SS.

Immunogenetics of the Neonatal Lupus Syndrome

Abstract Infants with neonatal lupus erythematosus have congenital heart block, transient cutaneous lesions, or both. Mothers of these infants have SSA/Ro autoantibodies that are passed across the ...

Primary Sjögren's syndrome in men:Clinical, serologic, and immunogenetic features

Although primary Sjögrens syndrome is a common rheumatic disorder in women, it is not well recognized in men. This study represents the first report of the clinical, serologic, and immunogenetic features of a group of 36 men with primary Sjögrens syndrome, which are contrasted with those of a group of 69 women with primary Sjögrens syndrome. The majority of male patients had extraglandular involvement including articular (78 percent), neurologic (39 percent), inflammatory vascular (25 percent), and lymphoproliferative disorders (17 percent). Although men were at the same risk for the development of extraglandular complications, there were significant serologic and immunogenetic differences. In sharp contrast to women with Sjögrens syndrome, men with Sjögrens syndrome were seronegative with respect to the presence of serum rheumatoid factor (p = 0.008) and antibodies to Ro(SS-A) (p = 0.016). The supertypic specificity, MT2 (DRw52), as in women, was strongly associated with primary Sjögrens syndrome in men when compared with race-matched control subjects (p = 0.0015). In men, however, the frequency of HLA-B8 and HLA-DR3, the most common DR locus specificity observed in women, was not statistically different from that observed in the normal control group.

Magnetic resonance imaging of cerebral lesions in patients with the Sjögren syndrome.

Thirty-eight patients with the primary Sjögren syndrome, 16 with active neuropsychiatric manifestations and 22 without clinical evidence of central nervous system involvement had magnetic resonance (MR) imaging. Eight patients had focal neurologic deficits (6 of these also had psychiatric, or cognitive dysfunction), and 8 had psychiatric or cognitive abnormalities alone. Magnetic resonance imaging showed abnormal results in 12 of 16 (75%; 95% CI, 48 to 93) patients with active central nervous system disease (67 focal lesions predominantly within the subcortical and periventricular white matter), and in 2 of 22 (9%; 95% CI, 1 to 29) patients without clinical evidence of central nervous system disease (P less than 0.0001). Seven of eight patients with focal neurologic deficits and 5 of 8 patients with psychiatric or cognitive dysfunction alone had abnormal results on MR imaging. Magnetic resonance imaging was more sensitive in the subgroup with focal deficits, (sensitivity, 88%; 95% CI, 44 to 97) than computerized axial tomography or cerebral angiography. Magnetic resonance imaging detects focal cerebral lesions in patients with the Sjögren syndrome and central nervous system involvement, including patients with psychiatric and cognitive dysfunction alone.