Diagnosis of latent tuberculosis infection with T-SPOT(®).TB in a predominantly immigrant population with rheumatologic disorders.

PURPOSE: The objective of this study is to compare how likely positive tuberculin skin test (TST) and T-SPOT(®).TB (TSPOT) results predict risk factors for tuberculosis in a predominantly immigrant patient population at risk of latent TB infection (LTBI) and with rheumatologic conditions requiring immunomodulatory therapy (IMT). METHODS: Prospective study conducted at a referral rheumatology clinic. Inclusion criteria included patients on various IMT, including immunosuppressive drugs that could predispose to TB progression. We studied risk factors associated with LTBI, test results, and tests' agreement. RESULTS: We studied 101 patients. Eighty (79.2 %) were from countries where TB is prevalent and Bacille Calmette-Guérin vaccination is placed routinely. Seventy-four (73.3 %) had rheumatoid arthritis and 92 (90.7 %) were on IMT. Among patients with both TST and TSPOT results, 25 (30.9 %) were TST(+) and 20 (24.7 %) had TSPOT(+) results. Fifteen patients (18.5 %) had TST(+)/TSPOT(+) results, and 51 (63.0 %) had TST(-)/TSPOT(-) results (agreement = 81.5 %; kappa = .54 [95 % CI, .34-.74; P < .001]). Each TSPOT(+) and TST(+) results were independently associated with immigrant status and prior residence in a TB prevalent country after adjustment for immunosuppressive therapy: Adjusted OR(TSPOT+)=6.6 (95 % CI, 1.2-123.3; P = .027); and adjusted OR(TST+)=11.2 (95 % CI, 2.0-209.5; P = .003). Seven out of 10 TST(+)/TSPOT(-) cases had a TST ≥15 mm induration, including three cases with history of TST conversion. CONCLUSIONS: TST(+) and TSPOT(+) results predict risk factors associated with LTBI independent of immunosuppressive IMT. Some TST(+)/TSPOT(-) results were unlikely to be false-negatives. The combined use of TST and TSPOT appears to be a reasonable diagnostic strategy to evaluate for LTBI in this population.

Potential Benefits of Psilocybin for Lupus Pain: A Case Report.

INTRODUCTION: Outcomes of treatment for patients with Lupus have shown overall improvement and benefit from the more aggressive use of immunosuppressants and biological agents through a treat-to-target approach. However, chronic musculoskeletal pain can be refractory to treatment despite the use of non-steroidal anti-inflammatory drugs, corticosteroids, and other analgesic agents, leading to patient dissatisfaction. The concept of new neural pathways from psilocybin usage has been proposed in a variety of pain syndromes; however, it is not trialed for patients with Lupus pain. CASE PRESENTATION: The patient was a 67-year-old male with positive anti-dsDNA antibody Lupus with a predominance of chronic polyarticular joint pain treated with hydroxychloroquine and non-steroidal anti-inflammatory drugs without pain relief. Pain dramatically improved after a one-time macro-dosing of 6 grams of Psilocybin cubensis in Oregon, which he expected would only provide a sense of enlightenment. After 12 months, he continued without debilitating joint pain. CONCLUSION: The serotonin-2A receptor's activation triggers an array of neurophysiological reactions that disrupt the functional connections in areas of the brain that are associated with chronic pain. These neuroplastic effects can generate healthy connections, resulting in long-lasting pain relief. However, this is a process that has not been fully analyzed. While there is anecdotal evidence to suggest the therapeutic benefits for autoimmune diseases, including rheumatoid arthritis and psoriasis, there is no specific research that explores its use for lupus-related pain. Since this is the first case that shows the benefit of psilocybin in a patient with Lupus, further studies on macro-dosing psilocybin to treat Lupus pain are warranted.

Pregnancy in a patient with gouty arthritis secondary to pseudo-Bartter syndrome.

A 32-year-old woman with pseudo-Bartter syndrome secondary to excessive use of laxatives, presented with hypokalemia, metabolic alkalosis, hyperuricemia, and gouty arthritis with tophi. Subsequently the patient became pregnant and displayed recurrent severe gouty flares of multiple joints. Monosodium urate crystals were aspirated from the knee confirming the diagnosis of gout. Previous reports have stated an association between Bartter syndrome and gout, but this is the first case report of a pregnancy with active gouty arthritis combined with pseudo-Bartter syndrome.

A patient with primary Sjogren's syndrome, cystic lung disease, and MALT lymphoma treated successfully with rituximab: a case-based review.

Primary Sjogren's syndrome (pSS) can have a myriad of presentations, ranging from mild xerostomia to more diffuse systemic involvement. It is well established that pSS is associated with a variety of pulmonary pathologies, and it is also known that pSS patients are at higher risk for lymphoma development. Here, we present an unusual case of a woman with primary Sjogren's syndrome who had both diffuse cystic lung disease as well as extranodal MALT lymphoma, successfully treated for both conditions with the CD-20 monoclonal antibody rituximab.

Low Dose Naltrexone in the Treatment of Fibromyalgia.

BACKGROUND: ConclusionFibromyalgia is a chronic pain disorder characterized by diffuse musculoskeletal pain, fatigue, sleep disturbance and cognitive impairment. OBJECTIVE: A significant number of fibromyalgia patients do not respond adequately to the current drugs approved by the Food and Drug Administration (FDA) for fibromyalgia treatment including pregabalin, milnacipran, duloxetine. Thus, there is still a need for adjunctive therapies. METHOD: Naltrexone is an opioid receptor antagonist used to treat alcohol and opioid dependence. It is hypothesized that low dose naltrexone causes transient blockade of opioid receptors centrally resulting in a rebound of endorphin function which may attenuate pain in fibromyalgia. RESULTS: Two small prospective pilot studies have previously shown that treatment with low dose naltrexone may be an effective, safe, and inexpensive treatment for fibromyalgia. CONCLUSION: This prospective study lends further support to the preliminary body of evidence that naltrexone is a well tolerated and likely effective treatment option in the community setting. Further large prospective controlled trials are still needed.

Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren's Syndrome patients.

Cathepsin S (CTSS) activity is elevated in Sjögren's Syndrome (SS) patient tears. Here we tested whether protease inhibition and cystatin C (Cys C) levels are reduced in SS tears, which could lead to enhanced CTSS-driven degradation of tear proteins. CTSS activity against Cys C, LF and sIgA was tested in SS or healthy control tears. Tears from 156 female subjects (33, SS; 33, rheumatoid arthritis; 31, other autoimmune diseases; 35, non-autoimmune dry eye (DE); 24, healthy controls) were analyzed for CTSS activity and Cys C, LF, and sIgA levels. Cys C and LF showed enhanced degradation in SS tears supplemented with recombinant CTSS, but not supplemented healthy control tears. CTSS activity was significantly increased, while Cys C, LF and sIgA levels were significantly decreased, in SS tears compared to other groups. While tear CTSS activity remained the strongest discriminator of SS in autoimmune populations, combining LF and CTSS improved discrimination of SS beyond CTSS in DE patients. Reductions in Cys C and other endogenous proteases may enhance CTSS activity in SS tears. Tear CTSS activity is reconfirmed as a putative biomarker of SS in an independent patient cohort while combined LF and CTSS measurements may distinguish SS from DE patients.

Quest for the Holy Grail to cure arthritis and osteoporosis: emphasis on bone drug delivery systems.

The number of new medications to treat and even prevent arthritis and osteoporosis has expanded dramatically in recent years. Where once there were only surgical options to treat such end-stage diseases, there are now treatments targeted at the early steps in musculoskeletal pathophysiology. The use of different modalities to maximize drug access to specific bone tissues has created a golden opportunity for mechanistic studies in drug delivery systems for treating osteoporosis and other musculoskeletal diseases. This theme issue provides a timely analysis of the challenges and accomplishments in delivering medicine to the target sites in the musculoskeletal system and also provides a preview of what may come in the future for musculoskeletal medicine. As the number of animal studies and clinical trials is on the rise, the possibility to prevent or even cure the aforementioned disorders has never been closer.

Priapism after tumor necrosis factor alpha inhibitor use.

We present a possible important association of tumor necrosis factor-alpha inhibition (TNFa-i) and erectile function in a male patient with rheumatoid arthritis (RA). Long-standing, untreated RA may result in significant physical limitation and disability, however often overlooked is the association between RA and erectile and sexual dysfunction. Ischemic priapism is currently unrecognized as an adverse reaction associated with TNFa-i use and there have been no reported cases with adalimumab. Our patient, a 58-year-old Hispanic man, with sero-positive, erosive RA developed persistent priapism (17 days) despite multiple urologic interventions after initial adalimumab 40 mg administration. TNFa has recently been implicated as a potential factor in erectile dysfunction through its role in vascular reactivity. Excess TNFa, from active RA, may perturb intracavernosal smooth muscle and endothelial cell function; theoretically, TNFa inhibition may then causes excess local nitric oxide production and subsequent priapism. The potential role of TNFa-i in ED and risk for priapism is an important area for future study.

Inflammatory Fibromyalgia: Is it Real?

Fibromyalgia (FM) is a characterized by generalized pain with widespread tender points in specific areas and is frequently accompanied by fatigue, stiffness, and a non-restorative sleep pattern. In the current retrospective study, we identified a subgroup of FM patients who had clinically important markers of inflammation. The study also explored the use of the original American College of Rheumatology (ACR) criteria in the diagnosis of FM. Our data suggested there was a distinct subset of patients with FM who had positive ESR, CRP, ANA and RF; a group that we considered representative of inflammatory FM. None of the FM patients in this study developed a documented coexisting autoimmune illness during the retrospective review period. The existence of FM subgroups further puts into question the already controversial use of either the new or old ACR classification criteria in the diagnosis of FM, as they do not address the issue of systemic inflammation which appears to be significant.

Giant cell arteritis with visual loss following zoledronic acid infusion.

Zoledronic acid is used in the treatment of osteoporosis. Giant cell artertitis may lead to vision loss. We report a case in which vision loss occurred after zoledronic acid infusion.

Tear cathepsin S as a candidate biomarker for Sjögren's syndrome.

OBJECTIVE: The diagnosis of Sjögren's syndrome (SS) in routine practice is largely a clinical one and requires a high index of suspicion by the treating physician. This great dependence on clinical judgment frequently leads to delayed diagnosis or misdiagnosis. Tear protein profiles have been proposed as simple and reliable biomarkers for the diagnosis of SS. Given that cathepsin S activity is increased in the lacrimal glands and tears of NOD mice (a murine model of SS), the aim of this study was to explore the clinical utility of using tear cathepsin S (CTSS) activity as a biomarker for SS. METHODS: A method to measure CTSS activity in tears eluted from Schirmer's test strips was developed and validated. Schirmer's tests were performed and CTSS activity measurements were obtained in 278 female subjects, including 73 with SS, 79 with rheumatoid arthritis, 40 with systemic lupus erythematosus, 10 with blepharitis, 31 with nonspecific dry eye disease, and 12 with other autoimmune diseases, as well as 33 healthy control subjects. RESULTS: The median tear CTSS activity in patients with SS was 4.1-fold higher than that in patients with other autoimmune diseases, 2.1-fold higher than that in patients with nonspecific dry eye disease, and 41.1-fold higher than that in healthy control subjects. Tear CTSS levels were equally elevated in patients with primary SS and those with secondary SS, independent of the Schirmer's test strip values or the levels of circulating anti-SSA or anti-SSB antibodies. CONCLUSION: Markedly high levels of tear CTSS activity are suggestive of SS. CTSS activity in tears can be measured in a simple, quick, economical, and noninvasive manner and may serve as a novel biomarker for autoimmune dacryoadenitis during the diagnostic evaluation for SS.

Immune thrombocytopenia in patients with connective tissue disorders and the antiphospholipid antibody syndrome.

It has been theorized that immune thrombocytopenia (ITP) is a syndrome characterized by various defects in immune regulation, resulting in a common phenotype, decreased blood platelets, and symptoms of mucocutaneous bleeding. Most often, successful treatment of the underlying connective tissue disorder with corticosteroids or other disease-modifying agents can simultaneously improve concurrent thrombocytopenia. The best evidence to date would support the targeting of treatment to the connective tissue disorder, expecting a simultaneous improvement in the platelet count. Due to the frequent relapses associated with many of the connective tissue disorders and the frequent use of immunosuppressant agents, splenectomy should be undertaken only in highly refractory patients. Differentiating the varying immunopathic etiologies that contribute to development of connective tissue disorders may lead to a better understanding of the mechanisms of thrombocytopenia in a subset of these patients. The use of target therapies to treat connective tissue disorders has the potential of reducing the risk of the development of ITP or, conversely, inducing the development of immune thrombocytopenia.