Samy Metyas

Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus

Objective: To assess longitudinal expression of a proliferation-inducing ligand (APRIL) in patients with systemic lupus erythematosus (SLE) and its correlation with B lymphocyte stimulator (BLyS) expression, serum anti-dsDNA titres, and clinical disease activity. Methods: Sixty eight patients with SLE were longitudinally followed up for a median of 369 days. At each visit the physician assessed disease activity by SLEDAI, and blood was collected for determination of serum APRIL and BLyS levels and of blood APRIL and BLyS mRNA levels. Fifteen normal control subjects underwent similar laboratory evaluation. Results: Dysregulation of APRIL was not as great as that of BLyS. Changes in serum levels of APRIL and BLyS over time were usually discordant, whereas blood levels of APRIL and BLyS mRNA strongly paralleled each other. Serum APRIL levels modestly, but significantly, inversely correlated with serum anti-dsDNA titres in anti-dsDNA positive patients analysed in aggregate. Moreover, serum APRIL levels modestly, but significantly, inversely correlated with clinical disease activity in all patients analysed in aggregate. Conclusion: Serum levels of APRIL and BLyS are differentially regulated. APRIL may serve as a down modulator of serological and/or clinical autoimmunity in patients with SLE. This may have important ramifications for BLyS targeted treatment, and it remains to be determined whether agents which neutralise only BLyS will be preferable to agents which neutralise both BLyS and APRIL.

Infliximab treatment of Familial Mediterranean fever and its effect on secondary AA amyloidosis.

We describe a patient with a long history of familial Mediterranean fever who developed proteinuria as a result of secondary AA amyloidosis. In this patient, the inflammatory process, including recurrent attacks of arthritis, abdominal pain, nephrotic syndrome secondary to amyloidosis, and high sedimentation rate, was rapidly suppressed by treatment with infliximab and there was remarkable improvement of the proteinuria. Because TNF-&agr; is a proinflammatory cytokine that plays a major role in FMF and secondary amyloid, it is an appropriate target for therapy. Our case is the first case of reactive systemic amyloidosis secondary to familial Mediterranean fever, which responded favorably to infliximab.

Neurosarcoidosis mimicking multiple sclerosis successfully treated with methotrexate and adalimumab

Dear Editor, A 54-year-old Hispanic woman presented to a rheumatology clinic with lower back pain and bilateral lower extremity weakness of 6 months duration. The patient’s pain was exacerbated with ambulation and standing for long periods of time. The patient also had headaches and mild confusion. She denied fever, chills, bowel or bladder incontinence, weight loss or eye inflammation. Her past medical and surgical history included migraine headaches, unspecified seizures, cervical spine fusion surgery and breast augmentation. There was a maternal family history of sarcoidosis. Physical examination revealed the patient to be afebrile with stable vital signs. Chest examination was normal. Neurological exam was significant for hyporeflexia and 4/5 strength in the bilateral lower extremities. Magnetic resonance imaging (MRI) of the spine revealed marrow edema and infiltrates in T2, T11, L5 and S1 (Fig. 1), suggesting possible osteomyelitis. The patient was subsequently hospitalized for intravenous antibiotics. The erythrocyte sedimentation rate was 40 mm/h (normal 0–30 mm/h) and C-reactive protein level was 13.2 mg/dL (normal 0–4.9 mg/dL). Serologic tests were all negative. A lumbar puncture was performed. Cerebrospinal fluid (CSF) was clear with a normal cell count and differentials and was negative for infection or malignancy. The patient subsequently underwent a T11 vertebral body biopsy. Biopsy showed non-caseating granulomas. Culture and acid fast bacilli (AFB) smear were negative. Pulmonary function tests revealed low lung volumes and decreased diffusion capacity suggestive of mild restrictive disease. Computed tomography (CT) scan of the chest showed bilateral ground glass appearance. Bronchoscopy was performed and bronchial alveolar lavage (BAL) revealed pulmonary macrophages with a few mixed inflammatory cells. Lung biopsy was performed and showed no evidence of granulomas. Brain MRI revealed active demyelination (Fig. 2). Angiotensin converting enzyme (ACE) level had been examined in the CSF and was elevated.

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.

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.

Autoinflammation and Immunomodulation in Inflammatory Fibromyalgia Syndrome- A Review

Generalized pain with tender points in specific areas accompanied by systemic symptoms such as fatigue and stiffness is characteristic of fibromyalgia (FM) syndrome. The genesis of FM is still being investigated with conflicting data on factors including autonomic dysfunction, neurotransmitters, and hormones often in combination with external stressful events. However, recent research is starting to suggest that there is a previously underappreciated subtype of fibromyalgia called inflammatory Fibromyalgia (iFM). Recent studies have described cytokines, inflammatory markers, sleep disorders, hyperalgesia, cognitive dysfunction, serum leptin levels and other inflammatory indicators as potential markers for iFM. This article will; 1) review the inflammatory markers and abnormal levels of other laboratory indicators that can help to identify the subgroup of patients that fall into the new category of Inflammatory Fibromyalgia [1-5] and 2) review all completed trials that were focused on treating this new category of disease. Through this review it is hoped that and further understanding of the complexity of the etiology of fibromyalgia can be explored.

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.

THU0355 Monotherapy versus combination therapy in the treatment of fibromyalgia

Background At the present time three drugs (pregabalin, duloxetine, milnacipran) are approved by the American Food and Drug Administration (FDA) for the treatment of fibromyalgia. There is no medication currently that is capable of complete symptom control, as the available drugs have been shown to improve only one or two fibromyalgia symptoms. Objectives The aim of the present study was to assess the potential additive or synergistic effects of combined pharmacotherapy in comparison to monotherapy in treatment of fibromyalgia. Methods This was a retrospective study reviewing 785 patients diagnosed with fibromyalgia. Pregabalin, flexibly dosed (50-450 mg/day), was administered to 122 fibromyalgia patients in combination with Duloxetine, also flexibly dosed (30-120 mg/day), or Milnacipran (25-200 mg/day). Three hundred and thirty-four patients were administered one of the three FDA approved drugs alone. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), The Brief Pain Inventory (BPI) and the patients’ Global Improvement scale (PGI). Emergent adverse reactions were also recorded. Results Treatment with pregabalin in combination with either duloxetine or milnacipran was superior to monotherapy in regards to improvements in fibromyalgia severity, sleep quality, depression and pain interference with daily activity. Combination therapy resulted in an improvement in the pain score of 29.3% when compared to that of monotherapy. Conclusions Treatment with combined pharmacotherapy significantly improved fibromyalgia severity and associated symptomatology. Combination therapy is synergistic in their effects and yields greater results in multiple symptom domains compared to that of monotherapy. Larger, prospective trials should be developed to test this conclusion and to assess safety and tolerability of combination therapy. Disclosure of Interest S. Metyas Consultant for: Pfizer Pharmaceuticals, M. Ibrahim: None Declared, E. Ortiz: None Declared, S. Maher: None Declared, D. Arkfeld Consultant for: Cypress Pharmaceuticals

AB0658 Low dose naltrexone in the treatment of fibromyalgia

Background Fibromyalgia is a chronic pain disorder characterized by diffuse musculoskeletal pain, fatigue, sleep disturbance and cognitive impairment. A significant number of fibromyalgia patients do not respond adequately to the current drugs (pregabalin, milnacipran, duloxetine) approved for fibromyalgia treatment by the Food and Drug Administration (FDA). Thus, there is still a need for adjunctive therapies. 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 fibromyalgia1. Objectives The aim of this study was to determine the effect of low dose naltrexone on symptoms in fibromyalgia. Methods This was a prospective, open label study carried out at a single center. Twenty-five patients diagnosed with fibromyalgia (according to the American College of Rheumatology criteria) participated. Naltrexone was started at a dose of 3 mg at night time and could be titrated up to a maximum of 4.5 mg at night time. Patients were permitted to continue pregabalin, milnacipran, or duloxetine. The primary outcome measure was the Revised Fibromyalgia Impact Questionnaire (FIQR) at month 3. Adverse reactions were also recorded. Results Twenty-four females and 1 male were enrolled. Twenty-two patients completed the study. Seven (32%) patients were on naltrexone monotherapy throughout the study. There was a 19.5% overall improvement in FIQR at month 3 with naltrexone therapy. Eleven (50%) had an average of a 41% improvement in the FIQR. The patients reported decreases in anxiety, pain and sleeping habits from baseline. Two patients discontinued the drug because they felt it was ineffective and 1 patient discontinued because of diarrhea. Conclusions Treatment with low dose naltrexone may be an effective, highly tolerable and inexpensive treatment for fibromyalgia. Further controlled trials are needed. References Ramanathan S, Panksepp J, Johnson B. Is fibromyalgia an endocrine/endorphin deficit disorder?Is it low dose naltrexone a new treatment option? Psychosomatics 2012;53:591-4. Disclosure of Interest None Declared