Biologic therapies in the treatment of sarcoidosis.

Sarcoidosis is a disease of remarkable heterogeneity in organ manifestation, severity and natural history, characterized by the presence of non-caseating granulomas. The majority of cases are acute and self-limited or remit with short courses of glucocorticoids; however, a proportion progress to a life-threatening obliterative fibrotic type associated with significant disability related to pulmonary, cardiac, ocular or central nervous system involvement. Biologic agents have been demonstrated in the successful treatment of refractory organ-threatening sarcoidosis; and though sarcoidosis remains elusive in predictability of progression, strong evidence suggests an indisputably efficacious role for these agents in efforts to stave morbidity and mortality related to sarcoidosis. This paper provides a review of sarcoidosis mechanistic etiopathogenesis to highlight the hypothetical underpinnings of the utility and concerns of current biologic treatments in current use and the potential future applications of newer agents and those under development.

Modulatory effects of proinflammatory cytokines for action cascading processes - evidence from neurosarcoidosis.

Neurosarcoidosis is a rare central nervous system manifestation of sarcoidosis. T cell, T-helper cell and macrophage activation via the major histocompatibility complex (MHC) II-mediated pathway causes this disease. Little is known about the possible cognitive disturbances in this disease as most reported instances are case studies. Here, we provide the first in-depth analysis of psychomotor functions in a sample of 30 neurosarcoidosis patients. We investigated action control processes using a paradigm that is able to examine how different tasks are cascaded to achieve the task goal. We integrated electrophysiological (EEG) data with behavioural and neuroimmunological data. Our results show that there was no general cognitive decline in patients with neurosarcoidosis. Patients only presented deficits when two response options have to be prioritized. Patients apply an inefficient processing strategy where they try to processes different response options in parallel. The electrophysiological data show that the deficits are due to dysfunctions at the response selection stage. Behavioural and neurophysiological changes are predictable on the basis of soluble interleukin 2 receptor serum concentrations. The results show that neurosarcoidosis is not associated with nonspecific changes in cognitive functions but does lead to specific alterations in cognitive control that are strongly dependent on immunological parameters.

Calcium and vitamin D in sarcoidosis: how to assess and manage.

The synthesis of vitamin D is altered by the granulomatous inflammation of sarcoidosis leading to increased production of 1, 25-dihydroxyvitamin D. Mounting evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. These and other extraskeletal health benefits have led to an increase in vitamin D assessment and pharmacological supplementation in the general population. This review highlights the altered synthesis and general immunomodulating properties of vitamin D with a special emphasis on known interactions with sarcoidosis. In addition, the assessment of vitamin D nutritional status, its pharmacological supplementation, and the management of bone health in patients with sarcoidosis are reviewed.

Antioxidant status associated with inflammation in sarcoidosis: a potential role for antioxidants.

RATIONALE: Enhanced production of reactive oxygen species (ROS), capable of reducing endogenous defense levels and enhancing inflammation, is suggested to play a role in sarcoidosis. Antioxidant supplementation might offer protection against such ROS-mediated damage. A promising candidate for antioxidant supplementation is the flavonoid quercetin. AIM: To determine the antioxidant and inflammatory status in sarcoidosis. Furthermore, the potential of quercetin to mitigate the occurring inflammation will be assessed. METHODS: Non-smoking sarcoidosis patients and healthy controls matched for age, gender and dietary behavior were enrolled (NCT-00512967). Measurements included assessment of total plasma antioxidant capacity, vitamin C, uric acid, glutathione, basal and LPS-induced levels of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-8 and -10 as well as the effect of quercetin on these levels. RESULTS: Compared to their controls, the sarcoidosis patients displayed significantly lower total plasma antioxidant capacity, decreased levels of vitamin C, uric acid and glutathione and increased levels of basal TNFalpha and IL-8. Quercetin significantly decreased ex vivo LPS-induced TNFalpha- and IL-8 production in a concentration-dependent manner in both groups. Interestingly, this quercetin effect was more pronounced in sarcoidosis patients. DISCUSSION: The endogenous antioxidant defense was significantly reduced in sarcoidosis, indicating that oxidative stress underlies the pathology of this disease. Furthermore, the inflammatory status was significantly enhanced in sarcoidosis. Finally, our results regarding the effect of quercetin on cytokine production imply that sarcoidosis patients might benefit from antioxidant supplementation not only by empowering the relatively low protection against ROS but also by reducing inflammation.

[Likopid in the complex immunomodulating treatment of patients with sarcoidosis of the lung and intrathoracic lymph nodes]. / Likopid v kompleksnom immunokorrigiruiushchem lechenii bol'nykh sarkoidozom legkikh i vnutrigrudnykh limfaticheskikh uzlov.

AIM: To examine the functional status of the immune system in patients with lung and intrathoracic lymph nodes sarcoidosis and to evaluate the efficiency of immunomodulation alone and in its inclusion in combined treatment of the disease. MATERIALS AND METHODS: 58 patients with the disease of varying severity were followed up. Comprehensive examination, involving clinical, immunological, X-ray, and physical studies, in patients treated with combined immunotherapy was performed. Initial examination revealed mixed immunodefficiency with impaired T- and phagocytic activity. According to the degree of immunological changes, the patients were given immunotherapy, including polyoxidonium, T-activin (or immunophan) injections, a complex of multivitamins and trace elements, and total adaptogens. After partial or complete normalization of an immunogram, all the patients received licopid (two-three 10-day courses, 10 mg/day). RESULTS: The optimal result (as long as 3-year remission) was achieved in the first time diagnosed sarcoidosis who have not taken glucocorticoidal hormones. CONCLUSION: The follow-up shows that addition of licopid is a compulsory component of immunotherapy in this disease; the efficiency of treatment is determined by its multimodality. The courses of therapy should be repeated when immunological indices deteriorated.

Sarcoidosis / Sarcoidosis

La sarcoidosis es una enfermedad granulomatosa sistémica caracterizada por la presencia histológica de granulomas no caseificantes. En este trabajo se ofrece una panorámica general de la enfermedad, su historia, hipótesis etiológicas, patología, inmunología y genética, cuadro clínico general y clasificación, dificultades diagnósticas y utilidad de los exámenes disponibles en la actualidad, evolución y forma de seguimiento. Por último, se expone el tratamiento con el esquema utilizado por uno de los Centros de mayor estudio de esta patología y el lugar que ocupan las drogas de segunda línea

[Löfgren syndrome after silicone breast prosthesis implantation]. / Szilikongél emlöprotézis beültetése után kialakult Löfgren-szindróma.

The authors review the case of a 30-year old female hair-dresser, into the breasts of whom silicone-gel implants have been implanted for cosmetic reasons. Ten months after the operation Löfgren-syndrome evolved, which improved only temporarily after the removal of the implants. The present symptom-free state, existing for 6 months now, required a 17-month corticoid therapy. The authors share the view that in rare cases silicon-gel implants might induce an autoimmune reaction, which is unforeseeable. When it is rightly presumed that human adjuvant disease or some other specified systemic disease is evolving, it is advisable that the implants should be removed and the patient should be treated with immunological therapy.

[Effect of acoustic stress on immunoregulatory cells in female patients with systemic lupus erythematodes (SLE), patients with sarcoidosis and normal comparative subjects]. / Einfluss von akustischem Stress auf immunregulatorische Zellen bei Patientinnen mit systemischem Lupus erythematodes (SLE), Patienten mit Sarkoidose und gesunden Vergleichspersonen.

14 patients with systemic lupus erythematosus (SLE), 12 with sarcoidosis and two age- and sex-matched groups of healthy subjects were exposed to a 10-minute acoustic stress test. Healthy subjects and patients with sarcoidosis showed significant increases in leukocyte and lymphocyte counts (p less than 0.01), relative elevations of B and Tsc lymphocytes (p less than 0.01) and a relative reduction of Th lymphocytes (p less than 0.01). Patients with SLE showed the same characteristic alterations (p less than 0.01) but the degree of this cell mobilization was significantly less pronounced as compared with the healthy subjects (p less than 0.01). No dependence was found between corticosteroid therapy or disease activity and the cellular reaction in SLE patients. In SLE patients there thus seemed to be an attenuated immune response due to stress which may play an etiopathogenetic role in this disease.