Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. Recently, a specific highly activated T helper cell subset, follicular helper T (Tfh) cell, has emerged as a key immunoregulator of germinal center (GC) formation and high-affinity antibody production. To identify the pathophysiological role of Tfh cells in SLE patients, we compared the phenotypic and functional properties of circulating Tfh-like cells in lupus patients to GC-Tfh cells, and correlated the percentage of Tfh-like cells with autoantibody production and SLE disease activity. METHODS: Peripheral blood was collected from 29 lupus patients and 25 healthy controls. Tonsils were obtained surgically from non-SLE controls and used as a source of GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, PD-1 and BTLA) via flow cytometry. IL-21 expression levels from Tfh cells were measured by real-time PCR and intracellular staining. The function of Tfh cells was carried out by co-culture of Tfh cells and autologous B cells in vitro. IgG in the culture supernatant was detected by ELISA. RESULTS: The frequency of circulating Tfh-like cells was significantly increased in SLE patients compared to healthy controls (p < 0.05). The Tfh-like cells not only display similar phenotypes and signature cytokines with GC-Tfh cells, but also are capable of driving B cells to differentiate into IgG-secreting plasma cells in vitro. In addition, the frequency of Tfh-like cells correlated positively with the percentage of circulating plasmablasts, levels of serum anti-dsDNA antibodies and ANA. CONCLUSION: The accumulated circulating Tfh-like cells in lupus patients share phenotypic and functional properties with GC-Tfh cells. Tfh-like cells may serve as perpetuators in the pathogenesis of SLE by enhancing the self-reactive B cell clones to further differentiate into auto antibody-producing plasmablasts, and ultimately cause autoimmunity.

Subacute abdominal pain requiring hospitalization in a systemic lupus erythematosus patient: a retrospective analysis and review of the literature.

In the systemic lupus erythematosus (SLE) patient, abdominal pain is a common problem. Intraabdominal vasculitis must be excluded as the source because of its potentially high mortality rate. We retrospectively reviewed the charts of 56 SLE patients with 75 admissions for predominantly subacute abdominal pain (abdominal pain without peritoneal signs) severe enough to require hospital admission, comparing the diagnostic modalities used, ultimate diagnoses, and use of corticosteroids before admission with 56 age- and sex-matched patients without SLE admitted for abdominal pain during the same time interval. SLE patients were further subdivided by disease activity at presentation using the SELENA SLEDAI score. The in-hospital mortality for all patients in this review was 0%. There were no statistically significant differences in the use of computed tomography between SLE and control patients. Intestinal vasculitis was diagnosed in 5.4% of SLE patients compared with 0% of control patients (P = 0.0433). Only patients with SLEDAI scores >8 developed vasculitis (P < 0.001). We recommend the routine use of computed tomography to diagnose vasculitis only in patients with SLEDAI scores >8 and subacute abdominal pain. All SLE patients with SLEDAI scores <8 and subacute abdominal pain should be evaluated for a cause of abdominal pain other than vasculitis.

New-onset systemic lupus erythematosus during chronic dialysis and after transplantation for idiopathic renal failure.

The onset of end-stage renal disease typically leads to quiescence of systemic lupus erythematosus clinical and serologic activity. We report two cases of systemic lupus erythematosus diagnosed for the first time years after dialysis and transplantation, respectively, for idiopathic end-stage renal disease. The transplant patient developed SLE despite ongoing treatment with prednisone and cyclosporine. New onset SLE can occasionally occur despite dialysis or transplantation.

Low back pain: how to make the diagnosis in the older patient.

Low back pain is a common complaint in primary care practice, particularly among older patients. The office-based workup starts with a careful history aimed at determining the onset, location, and severity of pain. A physical examination includes attention to gait, palpation, and some simple neurologic tests. Most patients require plain x-rays. Bone scans are useful for identifying suspected tumors and infections; CT and MRI are indicated in specific cases. Although the origin of most low back pain is indeterminate, the workup may uncover some important causes in older adults, including lumbar spinal stenosis, osteoporotic vertebral fractures, and metastatic disease to the spine.

Total joint replacement of the hip and knee.

Total hip and knee replacements are among the most common orthopedic surgical procedures performed on patients with arthritis. The procedures are highly successful in appropriately selected patients. The authors approach total joint replacement from a medical perspective, emphasizing indications, contraindications, preoperative evaluation, clinical outcome, and potential complications.

Chronic fatigue syndrome.

The chronic fatigue syndrome (CFS) is a poorly understood condition with nonspecific signs and symptoms, especially debilitating fatigue. Most patients can pinpoint the onset of their illness and usually describe a flu-like state. The search for an etiologic agent has focused on a number of viruses such as Epstein-Barr, enteroviruses, retroviruses, and human herpesvirus-6. Evidence supports persistent viral infection in a small percentage of CFS patients. Immunologic abnormalities do exist in CFS, which indicate the presence of immune activation in CFS patients. Although abnormal muscle biopsies have been found in some patients with CFS, strength and endurance appear normal, but perception of exertion may be abnormal. Patients with chronic fatigue have a high incidence of premorbid and concurrent psychiatric disorders, and on physical examination many often have reproducible tender points similar to fibromyalgic patients. Clinical evaluation should rule out other potential causes of fatigue, but elaborate diagnostic tests are seldom required. Presently, no specific treatment exists for CFS. A cognitive behavioral approach with or without the use of tricyclics has been advocated. Patients should be encouraged to maintain functional status and should not be discouraged from exercise. Several medications have been tried but with no definite clinical benefit.

Reactive arthritis due to hidradenitis suppurativa mimicking osteomyelitis.

We have reported a case of erosive arthritis of the hand preceding the appearance of hidradenitis suppurativa in the ipsilateral axilla, which was mistaken for osteomyelitis. Recognition of this presentation is important to avoid unnecessary invasive diagnostic procedures and to initiate prompt treatment directed at the underlying cause.

Whipple's disease with axial and peripheral joint destruction.

A seropositive white man had follow-up for 16 years with a diagnosis of palindromic rheumatism. Treatment had included parenteral gold, methotrexate, prednisone, hydroxychloroquine sulfate, and penicillamine before diarrhea led to a biopsy-proven diagnosis of Whipple's disease. Clinical and radiographic criteria for ankylosing spondylitis were met. In addition to classic Whipple's arthropathy, he had the combined but singular findings of pancarpal destruction and cervical apophyseal fusion. HLA typing revealed the B7 antigen. This case illustrates the pitfalls in diagnosis of a chronic polyarthritis that has, as a typical feature, a long latency before manifesting its more specific signs and symptoms (ie, diarrhea, malabsorption, and hyperpigmentation). Care should be taken during evaluation of any disease with atypical and nonspecific features (eg, positive rheumatoid factor in a patient with polyarthritis) and one should continue to reevaluate the original impression while confirmatory evidence is lacking. Moreover, the roentgenographic findings of pancarpal narrowing, apophyseal fusion, and advanced iliofemoral joint disease, in addition to sacroiliitis and syndesmophyte formation, challenge the generally held notion that Whipple's arthropathy is a nondestructive joint disease.

Pellegrini-Stieda syndrome mimicking acute septic arthritis.

This case illustrates the potential severity of an uncommon and generally benign condition of the knee--the Pellegrini-Stieda syndrome. The regional bone scan clearly showed the etiologic role of the inflamed ligamentous attachment site. Therapy should include joint rest, nonsteroidal anti-inflammatory agents, and possibly ice for symptomatic relief.

Osteoarthritis: increasing mobility and reducing disability.

Older patients taking NSAIDs or high-dose aspirin should have complete laboratory evaluations of blood count, urinalysis, BUN/creatine, potassium, and serum transaminases several times yearly; more often if the clinical picture warrants. The use of aspirin, NSAIDs, and other medications should be reviewed in detail with the patient, particularly the rationale. The physician should stress the need to take the medications regularly, not "as needed." Physicians should also take time to warn patients against unorthodox medications and "treatments."

Systemic lupus erythematosus (SLE) induced by quinidine.

Only two definite cases of quinidine-induced systemic lupus erythematosus (SLE) are reported in the English-language literature. We have treated five patients who had an SLE-like syndrome while receiving quinidine. Symptoms, signs, and abnormal laboratory values improved after quinidine therapy was discontinued and prednisone therapy was started. The disease did not return after steroids were withdrawn. These cases indicate that quinidine can indeed cause an SLE-like syndrome.

Protease inhibitors in inflammatory synovial effusions.

Granulocyte lysosomal enzymes can potentially participate in cartilage degradation in inflammatory arthritides. However, we have shown that the quantity of several such enzymes in an inflammatory synovial effusion correlates negatively with the degree of radiographic damage of the joint from which the fluid was sampled. In the current work the quantity of the following 5 protease inhibitors was determined immunochemically in the same fluids: alpha 1 antitrypsin, alpha 1-antichymotrypsin, alpha 2-macroglobulin, inter-alpha-trypsin inhibitor, and Cl esterase inhibitor. These inhibitors are generally covariate and correlate positively with the total protein in the fluid as well as the number of granulocytes and the concentration of granulocyte lysosomal enzymes in the fluid. As did the lysosomal enzymes, the protease inhibitors correlate negatively with radiographic destruction. It is likely that lysosomal enzymes in solution in inflammatory synovial effusions are rendered effete by the presence of protease inhibitors.

Lysosomal enzymes in inflammatory synovial effusions.

The concentrations of several polymorphonuclear neutrophilic lysosomal constituents were quantitated by immunochemical and enzymatic assays in 28 inflammatory and 9 noninflammatory synovial fluids. The quantities of lactoferrin, myeloperoxidase, and enzymatically determined lysozyme were covariate with the neutrophil count. Enzymatic activities measured with synthetic substrates developed for the assay of chymotryptic-like cationic protein (cathepsin G) and elastase, along with immunochemically determined lysozyme, were independent of the neutrophil count. Although the latter assays were developed and standardized with human neutrophilic lysosomal constituents, they measure different activities in inflammatory synovial effusions. No elastase was detected if elastin was used as the substrate. Regardless of the source of the enzymes, there was a negative correlation between their concentration and the degree of radiographic destruction of the joint from which the fluid was obtained. Lysosomal enzymes in solution in synovial fluid are not likely to be primarily involved in cartilage destruction.