Pancreatitis leading to thrombotic thrombocytopenic purpura in systemic lupus erythematosus: a case report and review of literature.

Pancreatitis is a well-established but unusual complication of thrombotic thrombocytopenic purpura (TTP). It is also an unusual complication of systemic lupus erythematosus (SLE). However, TTP occurring as a consequence of acute pancreatitis in a patient with SLE has never been reported. We report a 24-year-old African American woman with active systemic lupus (SLE) who developed thrombotic thrombocytopenic purpura (TTP) following an episode of acute pancreatitis. The TTP was manifested by low-grade fever, microangiopathic hemolytic anemia, renal insufficiency, altered mental status, seizures and thrombocytopenia. The patient was initially treated with pulse corticosteroids with inadequate response and subsequently with daily plasmaphresis, leading to full remission. This case represents first report of pancreatitis leading to TTP in a patient with systemic lupus erythematosus.

Antiphospholipid (Hughes') syndrome in African-Americans: IgA aCL and abeta2 glycoprotein-I is the most frequent isotype.

Antiphospholipid (Hughes') syndrome (APS) has not been reported in African-Americans (A-A) as frequently as in other ethnic groups. We describe eight A-A female patients with APS, including two cases of primary APS (PAPS), four with APS secondary to systemic lupus erythematosus (SLE), one with Sjögren's syndrome, and one with overlap connective tissue disease (CTD). Their mean age was 34 y (range 24-47 y). Patients were followed for a mean of 6 y (range 0.3-11 y). During follow up, both anticardiolipin (aCL) and anti-beta2glycoprotein-I (abeta2GPI) antibodies were measured in stored sera by enzyme-linked immunosorbent assay (ELISA). IgA was the most frequent isotype of aCL and abeta2GPI, and co-occurred with the IgM isotype in three of four patients with neurologic manifestations.

Autoantibody profile in African-American patients with lupus nephritis.

Lupus nephritis (LN) is one of the major risk factors for morbidity and overall mortality in systemic lupus erythematosus (SLE). Its pathogenesis is multifactorial, and a number of risk factors, including serological markers, have been identified in recent years, correlating with clinical course and disease severity. Furthermore, a distinctive autoantibody profile has recently been reported in African-American SLE women with LN. The aim of this study was to characterize the autoantibody profile in 222 African-American SLE patients, 94 with LN and 128 without. Only anti-dsDNA achieved statistical significance between the two groups (P < 0.05). Fourteen (14.9%) patients with LN and 15 (11.7%) without it exhibited positive anti-Ro/SS-A, anti-Sm, and anti-nRNP, but without anti-La/SS-B (P > 0.6). We conclude that African-American SLE patients with LN do not exhibit a specific or distinctive autoantibody profile. However, our data confirm the value of anti-dsDNA in SLE patients with LN.

Familial anticardiolipin antibodies and C4 deficiency genotypes that coexist with MHC DQB1 risk factors.

OBJECTIVE: To investigate the familial basis of antiphospholipid antibodies by studying putative risk factors at the C4 and MHC class II loci. METHODS: Autoimmune diseases, anticardiolipin (aCL) and other autoantibodies were studied in 38 first and 2nd degree family members of 3 index cases selected for primary antiphospholipid syndrome (APS) and 33 controls. C4 protein phenotyping and restriction fragment length polymorphism analysis of C4 and MHC class II loci were performed. RESULTS: Nineteen family members (46%) had autoimmune diseases or autoantibodies; aCL were present in 10 family members, 4 of whom had primary APS. Each family had 2 or more subjects with aCL. Among 22 independent haplotypes in family members, there was a high frequency of C4A and C4B deficiency alleles (0.41 vs 0.18 in 66 controls, p = 0.03) and a strong trend toward an increase in MHC DQB1 putative risk factors that share the TRAELDT structural domain. This DQB1 structural domain was present in 4/5 different haplotypes that contained a C4B deficiency genotype; however, neither of 2 different haplotypes with a C4A deletion (one being a common ancestral haplotype) contained this DQB1 putative risk factor. Among the 10 family members who had aCL, 10/20 haplotypes contained a C4 deficiency genotype; moreover, the DQB1 putative risk factor was present in all 16 MHC haplotypes that did not contain a C4A deletion. CONCLUSION: In these families, expression of an autoimmunity trait as aCL antibody appears to be associated with the coexistence of C4 deficiency alleles with DQB1 alleles that contain the TRAELDT structural domain.

Serum antinuclear antibodies in women with silicone breast implants.

OBJECTIVE: Recent evidence suggests that immunologic abnormalities are not uncommon in individuals with silicone breast implants. The purpose of our study was to evaluate in a consecutive manner, the prevalence of autoimmunity as assessed by the presence of antinuclear antibodies in a larger number of patients with silicone breast implants. METHODS: Antinuclear antibody (ANA) testing using an indirect immunofluorescence technique was performed on 813 individuals with silicone breast implants. All subjects except for 3 transsexual males, were female. The overwhelming majority, over 99%, were white. The average age of the subjects was 46.2, with a range of 17 to 72 years. RESULTS: ANA positivity was found in 244 of 813 individuals (30%) using a mouse kidney substrate; and in 470 of 813 (57.8%) using a HEp-2 cell line. The most common immunofluorescent pattern found using HEp-2 was speckled, present in 341 (72.5%) individuals, followed by homogeneous pattern in 113 (24%), nucleolar in 63 (13.4%), and 5 (1.06%) were anticentromere. Anti-dsDNA antibodies measured by an ELISA assay were found in 6 of 71 patients (8%). Rheumatoid factor and C-reactive protein were found above healthy controls in less than 10% of cases studied. The high prevalence of ANA found in patients with silicone breast implants agrees with similar observations by others. The finding of anticentromere and nucleolar patterns has great interest and relevance. These fairly distinct ANA patterns are most commonly seen in the idiopathic form of scleroderma and related conditions. CONCLUSION: These findings suggest that ANA positivity is relatively common in individuals with silicone breast implants, and may support the existence of autoimmune mechanisms in the pathogenesis of the clinical manifestations seen in this population.

Fibroblast function in psoriatic arthritis. I. Alteration of cell kinetics and growth factor responses.

OBJECTIVE: To explore the potential role of fibroblasts in the pathogenesis of psoriasis and its related arthritis. Specifically, we analyzed the cell cycle of psoriatic fibroblasts obtained from skin and synovium by flow cytometry, and we also studied their response to several growth factors. METHODS: Fibroblast cultures were established from normal and psoriatic skin, uninvolved and involved, and synovium. NIH-3T3 cells were also used as indicator cells in some of the experiments. Fibroblasts DNA cell cycle analysis was performed by flow cytometry, and the data was analyzed by using the "Cytologic DNA applications software version 2." In addition, fibroblasts were stimulated with growth factors including epidermal growth factor, transforming growth factor-beta, and platelet derived growth factor. RESULTS: A significant increase of S and G2-M phase values in confluent cultures of psoriatic fibroblasts in both skin and synovium compared to normal fibroblasts was found. Psoriatic fibroblasts also exhibited a greater proliferative response to growth factors compared to normal fibroblasts. CONCLUSION: Data obtained clearly showed a significant intrinsic in vitro alteration in skin and synovium fibroblasts from patients with psoriasis.

Fibroblast function in psoriatic arthritis. II. Increased expression of beta platelet derived growth factor receptors and increased production of growth factor and cytokines.

OBJECTIVE: The main objective was to investigate the expression of platelet derived growth factor (PDGF) receptors, and production of growth factors and cytokines from psoriatic skin and synovium derived fibroblasts. METHODS: Fibroblast cultures were established from normal and psoriatic skin and synovium. Confluent cultures of fibroblasts were used for a receptor binding assay for PDGF, and then extracts were run on Western blot. The amount of immunoreactive A and B chain peptides present was determined with specific A or B chain antisera. Production of interleukin 1 beta and PDGF-beta was accomplished by neutralization with the use of commercially available antisera. A functional assay was used to measure transforming growth factor-beta (TGF-beta). RESULTS: There was an increased expression of the beta PDGF receptor in the psoriatic fibroblasts. Interleukin 1 beta and PDGF-beta production by psoriatic fibroblasts was also increased. However, TGF-beta production was similar in normal and psoriatic fibroblasts. CONCLUSION: Our data demonstrate an increased expression of beta PDGF receptor, and production of IL-1 beta and PDGF by psoriatic fibroblasts. The findings provide further support for an active role of this cell line in the pathogenesis of psoriasis and psoriatic arthritis.

Hyperprolactinemia in Reiter's syndrome.

OBJECTIVE: Accumulated evidence suggests that certain immunoregulatory hormones including prolactin (PRL) may play a role in the pathogenesis and disease expression of certain autoimmune diseases. Our objective was to investigate the possible role of PRL in the pathogenesis and disease expression of the spondyloarthropathies, including Reiter's syndrome (RS). METHODS: Basal levels of PRL (serum) were determined by radioimmunoassay in patients with various types of spondyloarthropathies, patients with acute anterior uveitis (AAU), and healthy controls. Clinical manifestations at the time of serum collection were correlated with PRL levels. RESULTS: Hyperprolactinemia (PRL > 20 ng/ml) was found in 9 of 25 (36%) patients with RS. In contrast, only 1 of 34 (2.9%) (p < 0.001) patients with ankylosing spondylitis and none of the patients with psoriatic arthritis, AAU or healthy controls had hyperprolactinemia. The frequency of conjunctivitis, urethritis, dysentery, and uveitis was higher in hyper than in normoprolactinemic patients with RS. CONCLUSION: Our results suggest a possible role for this immunoregulatory hormone in the pathogenesis and disease expression of RS.

Pneumatosis cystoides intestinalis in systemic lupus erythematosus with intestinal vasculitis: treatment with high dose prednisone.

Pneumatosis cystoides intestinalis (PCI) is an uncommon disorder usually associated with intestinal and pulmonary obstructive diseases, recent abdominal procedures and systemic illnesses. PCI has been reported in patients with systemic lupus erythematosus associated with intestinal vasculitis. We describe herein a patient with a month history of intermittent abdominal pain, diarrhoea, hyporexia, and weight loss who underwent intestinal resection for acute abdomen. Post-operatively she gave a three-month history of arthritis of the right knee, ankles and feet, arthralgia of the wrists, MCPs and shoulders. She also described weakness, weight loss, Raynaud's phenomenon, and a skin rash. Laboratory examination revealed an increased ESR, low haemoglobin and haematocrit, positive rheumatoid factor, a positive ANA with a speckled pattern, as well antibodies to DNA, SS-A and cardiolipin. The abdominal symptomatology especially pain, cramps and bouts of diarrhoea persisted after the surgery and became worse two months later. Abdominal X-ray showed distention of bowel with cyst formation in the wall of the entire colon. A diagnosis of PCI was made radiologically. The intestinal pathology was reviewed and vasculitis was identified. The patient received treatment with high dose prednisone with an excellent response; prednisone was progressively tapered and she has been asymptomatic without abdominal complaints or other symptoms for over a year.

Seronegative antiphospholipid syndrome associated with plasminogen activator inhibitor.

Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, thrombocytopenia and is associated with the presence of antiphospholipid antibodies, especially anticardiolipin antibodies. We present a patient with the clinical features of antiphospholipid syndrome, namely recurrent venous and arterial thrombosis, recurrent abortions, thrombocytopenia and libido reticularis but with persistently negative serology for any type of antiphospholipid antibody. The possible existence of 'seronegative' antiphospholipid syndrome is proposed. Of additional interest in this patient is the presence of significantly elevated levels of plasminogen activator inhibitor. The role of this inhibitor, if any, in the antiphospholipid syndrome and/or seronegative antiphospholipid syndrome is not known and merits further study.

Ketorolac-precipitated asthma.

Ketorolac is an effective and popular long-lasting analgesic that is especially useful in the emergency department and postoperatively. It is comparable in potency to the opiates but is preferable to them in many instances. Its relative overall safety as compared to the opiate analgesics may generate an unjustified complacent attitude toward its safety in all instances. Ketorolac, however, is an NSAID, and its major toxicities include those of other NSAIDs. Bronchospastic- and anaphylactic-type life-threatening reactions have occurred with its use. The prescribing physician must be aware of this potential complication and should always obtain a patient's complete history, including information regarding aspirin and NSAID intolerance, asthma, rhinitis, and nasal polyps, before administering it. Its use is contraindicated under those circumstances. When ketorolac is administered to asthmatics, it should be done with extreme caution and monitoring, especially when the intramuscular preparation is used. In this way, morbidity, health care costs, and the potential for mortality will be kept at a minimum.

Antinuclear and antiphospholipid antibodies in healthy women with recurrent spontaneous abortion.

PROBLEM: To determine the presence of absence of subclinical autoimmunity in healthy women with first trimester recurrent spontaneous abortion (RSA), the sera of 72 healthy women with a history of three or more consecutive abortions were analyzed for the presence of antibodies to phospholipid and nuclear antigens. METHOD: Lupus anticoagulant was determined, as were antibodies to cardiolipin. An indirect immunofluorescent antinuclear test was performed and specific antinuclear antibodies to double-stranded DNA, ribonucleoprotein, Smith antigen, and Sjogren's syndrome A and B antigens were tested. RESULTS: Nine women (13.2%) had low levels of antinuclear antibodies, none of which were specific. Four women (5.6%) had moderate to high levels of aCL antibodies. CONCLUSION: We conclude that the prevalence of aCLs and antinuclear antibodies in healthy women with first trimester RSA is low. Subclinical autoimmunity is not a common cause of first trimester RSA.

Digital vasculitis following allergic desensitization treatment.

Systemic necrotizing vasculitis or a polyarteritis nodosa-like clinical presentation, is an unusual complication of immunotherapy (hyposensitization therapy). We describe a patient who developed features of vasculitis several years after beginning hyposensitization treatment for allergic rhinitis. In the 7 months preceding the onset of the vasculitis he experienced 4 episodes of anaphylaxis immediately after receiving desensitization injections. The vasculitis was characterized by the abrupt onset of pain and discoloration of the middle 3 digits of his right hand. Cyanosis and small areas of frank necrosis of these digits were present. Erythrocyte sedimentation rate and C-reactive protein were elevated and total serum complement was decreased. The development of digital vasculitis following hyposensitization is clearly illustrated in this patient.

Chlamydia-induced reactive arthritis.

Chlamydia trachomatis infection is now recognized as the most prevalent veneral disease in the Western World. The majority of cases of Reiter's syndrome, one type of reactive arthritis, are secondary to sexually transmitted infections. Evidence of urogenital C. trachomatis infection is found in 36% to 61% of cases of Reiter's syndrome. We investigated the prevalence of infection by this organism in a group of patients with spondyloarthropathies. Positive cultures were obtained in 39.4% of patients with Reiter's syndrome, as well as in 22.2% of patients with psoriatic arthritis and in 20% of patients with ankylosing spondylitis. An important percentage of patients also had positive serum antibodies against C. trachomatis (62.1% of patients with Reiter's syndrome), suggesting presence of infection at some point during the course of the disease. Our findings and those from other authors support the use of long-term antibiotic therapy in patients with reactive arthritis, mainly in those in whom positive culture for C. trachomatis has been obtained as well as in their sex partners.

Gonococcal arthritis.

Disseminated gonococcal infection is a preventable communicable disease. It is an important cause of arthritis in sexually active adults. Prompt recognition and treatment of this common disease results in cure and eliminates unnecessary diagnostic procedures and prolonged hospitalization.

Candida arthritis.

Septic arthritis can be caused by Candida species. Its true incidence is unknown because only a few cases have been reported. Two clinical syndromes have been identified. The first is an isolated monarthritis caused by the direct intra-articular inoculation of fungi that inhabit the skin, by means of an injection, or during surgery. The second is the development of a mono- or polyarthritis as a complication of hematogenously disseminated candidiasis. The optimum treatment of this condition is not yet known, although the combination of medical and surgical treatment seems to be the most convenient therapeutic modality. Amphotericin-B continues to be the drug of choice.