Elske Hoitsma

Neurosarcoidosis: a clinical dilemma

Sarcoidosis is an inflammatory multisystem disorder of unknown cause. Practically no organ is immune to sarcoidosis; most commonly, in up to 90% of patients, it affects the lungs. The nervous system is involved in 5-15% of patients. Neurosarcoidosis is a serious and commonly devastating complication of sarcoidosis. Clinical diagnosis of neurosarcoidosis depends on the finding of neurological disease in multisystem sarcoidosis. As the disease can present in many different ways without biopsy evidence, solitary nervous-system sarcoidosis is difficult to diagnose. Corticosteroids are the drug of first choice. In addition, several cytotoxic drugs, including methotrexate, have been used to treat sarcoidosis. The value of new drugs such as anti-tumour necrosis factor alpha will be assessed. In this review we describe the clinical manifestations of neurosarcoidosis, diagnostic dilemmas and considerations, and therapy.

Safety and Efficacy of ARA 290 in Sarcoidosis Patients with Symptoms of Small Fiber Neuropathy: A Randomized, Double-Blind Pilot Study

ARA 290 (a peptide designed to activate the innate repair receptor that arrests injury and initiates cytoprotection, antiinflammation and healing) reduces allodynia in preclinical neuropathy models. We studied the safety and efficacy of ARA 290 to reduce symptoms of small fiber neuropathy (SFN) in patients with sarcoidosis. A total of 22 patients diagnosed with sarcoidosis and symptoms of SFN were enrolled in a double-blind, placebo-controlled exploratory trial consisting of three times weekly intravenous dosing of ARA 290 (2 mg; n = 12) or placebo (n = 10) for 4 wks. Inclusion criteria were a diagnosis of neuropathy and a spontaneous pain score of ≥5 (Brief Pain Inventory [BPI]). Endpoints assessed were changes in pain intensity and the small fiber neuropathy screening list (SFNSL) score, quality of life (SF-36), depressive symptoms (Inventory of Depressive Symptomatology [IDS]) and fatigue (Fatigue Assessment Scale [FAS]). No safety concerns were raised by clinical or laboratory assessments. The ARA 290 group showed significant (p < 0.05) improvement at wk 4 in SFNSL score compared with placebo (Δ −11.5 ± 3.04 versus Δ −2.9 ± 3.34 [standard error of the mean]). Additionally, the ARA 290 group showed a significant change from baseline in the pain and physical functioning dimensions of the SF-36 (Δ −23.4 ± 5.5 and Δ −14.6 ± 3.9, respectively). The mean BPI and FAS scores improved significantly but equivalently in both patient groups. No change was observed in the IDS. ARA 290 appears to be safe in patients with sarcoidosis and can reduce neuropathic symptoms.

Association of the TNF-α G-308A polymorphism with TNF-inhibitor response in sarcoidosis

Responsiveness to tumour necrosis factor (TNF) inhibitors has been associated with the TNF-α G-308A polymorphism in rheumatoid arthritis. The aim of this study was to examine the association between the presence of this polymorphism and the response to TNF inhibitors in patients with refractory sarcoidosis. Patients (n=111) who started TNF-inhibitor treatment (76 infliximab, 35 adalimumab) were followed for at least 1 year. The main symptoms in these patients were fatigue (n=100, 90.1%), small fibre neuropathy (n=91, 82.0%), pulmonary involvement (n=69, 62.2%), and/or uveitis (n=31, 27.9%). Patients were additionally genotyped for the presence of the TNF-α G-308A polymorphism. Treatment response was assessed using clinical outcome measures and questionnaires. Three-quarters (n=83, 74.8%) of the patients responded well. Of the patients without the variant A-allele 93.6% (73 out of 78, p<0.001) improved, while 30.3% (10 out of 33) of variant A-allele carriers responded favourably to TNF inhibitors. For patients with the GG-genotype, the probability of improving compared with remaining stable or deteriorating was three times higher (risk ratio 3.09, 95% CI 1.84–5.20). Sarcoidosis patients without the TNF-α -308A variant allele (GG-genotype) had a three-fold higher response to TNF inhibitors (adalimumab or infliximab). Further research is needed to evaluate the value of genotyping for the TNF-α G-308A polymorphism in order to tailor TNF-inhibitor treatment. TNF-&agr; G-308A polymorphism predicts TNF-inhibitor response in refractory sarcoidosis: a step to personalised medicine? http://ow.ly/sQ7KO

The small fiber neuropathy screening list: Construction and cross-validation in sarcoidosis

BACKGROUND Small fiber neuropathy (SFN) appears to be relatively common in sarcoidosis patients. However, there is no golden standard to establish SFN and diagnostic tests for SFN are not widely available. There is a need for an easy to administer SFN screening instrument for clinical assessment, research or therapeutic trials. The aim of the present study was to develop a screening list to identify sarcoidosis patients with SFN in general clinical practice. METHODS We studied 139 sarcoidosis patients. The first consecutive 84 patients (Group 1) underwent temperature threshold testing (TTT) and completed an extensive SFN-symptoms-questionnaire. Based on data from Group 1 and using distribution measures and discriminant analyses, a screening list for SFN in sarcoidosis consisting of 21 questions was constructed: the Small Fiber Neuropathy Screening List (SFNSL). Subsequently, this SFNSL was crossvalidated in the next 55 consecutive patients (Group 2). RESULTS The same cut-off scores as found for Group 1 were appropriate in Group 2. The SFNSL was found to have high levels of internal consistency (Cronbachs alpha 0.90) and exploratory factor analysis showed that it measures only one underlying factor. Convergent validity seems good. CONCLUSION To assess the presence of SFN in clinical practice the SFNSL, a brief and easy to administer questionaire, was developed in a sarcoidosis population. The results of the present study support the idea that SFN is a serious problem in chronic sarcoidosis. Future studies are needed to establish the broad usefulness of this SFN screening list and expand knowledge on the psychometric properties.

A pragmatic approach to diagnosing and treating neurosarcoidosis in the 21st century

Purpose of review Neurosarcoidosis may be a serious complication of sarcoidosis. As the presentation of neurosarcoidosis is manifold, solitary nervous system sarcoidosis without systemic activity remains a difficult diagnosis. Appropriate treatment may be a dilemma. Recent findings Most neurosarcoidosis patients present with neurological symptoms as the first manifestation. Whole-body fluorodeoxyglucose positron emission tomography has been found useful in neurological patients suspected of sarcoidosis. Small-fiber neuropathy is commonly associated with sarcoidosis and can cause significant morbidity to afflicted patients. New drugs such as antitumor necrosis factor α have been proven valuable in the treatment of neurosarcoidosis in different locations. Progressive multifocal leucencephalopathy should be considered in neurosarcoid patients, especially when treatment fails. Summary In this paper an update on clinical manifestations of neurosarcoidosis, diagnostic dilemmas, and therapeutic options is provided.

Consequences of Sarcoidosis.

Sarcoidosis is a multisystem disorder of unknown cause(s). Less specific disabling symptoms, including fatigue and physical impairments, may have a major influence on the daily activities and the social and professional lives of the patients, resulting in a reduced quality of life. A multidisciplinary approach focusing on somatic and psychosocial aspects is recommended. Patients self-perceived knowledge about the importance of exercise and lifestyle should be improved. Developing the most appropriate therapeutic approach for sarcoidosis requires careful consideration of the possible impact of fatigue, small fiber neuropathy related symptoms, pain, cognitive functioning, and coping strategies. Personalized medicine and appropriate communication are beneficial.