First-line treatment of pulmonary sarcoidosis with prednisone or methotrexate

Sarcoidosis is an inflammatory multi-systemic disease of unknown origin with wide spectrum of clinical manifestations. Sarcoidosis may affect practically any organ — predominantly lungs, lymphatic system, skin, eyes alone or in combination. The disease is characterized by formation of non-caseous granuloma. In 1999 American Thoracic society (ATS), European Respiratory society (ERS) and World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) adopted an international consensus statement on diagnosis and treatment of sarcoidosis «Statement on Sarcoidosis». Based on ATS, ERS and WASOG 1999 Statement the national documents such as “Evidence-based adapted clinical guideline on sarcoidosis” and “Unified clinical protocol of primary, secondary (specialized) and tertiary (highly-specialized) medical care for sarcoidosis” approved by MOH of Ukraine (decree # 634 dated 08 Sep 2014) were developed by current authors in Ukraine. For a more detailed description of the principles of diagnosis and treatment of pulmonary sarcoidosis, we have developed and published methodological guidelines "Diagnosis of respiratory tract sarcoidosis" (2014) and "Treatment of pulmonary sarcoidosis" (2018). In 2020 ATS experts published an updated «Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline», according to which the diagnosis of sarcoidosis was based on 3 criteria: compatible clinical symptoms, presence of non-necrotizing granulomatous inflammation in one or more tissue samples (not always required) and exclusion of alternative causes of granulomatous disorder. Finally, in 2021 ERS task force report was published “ERS clinical practice guidelines on treatment of sarcoidosis”, which outlined completely new approaches to management of sarcoidosis patients. According to this document, a decision about treatment of patient depends on 2 major factors: risk of death or organ failure and deterioration of quality of life of a patient. In addition, main principle of management of sarcoidosis patients is a balance between: a) minimization of risk of disability or death due to lung injury and decrease of quality of life, and b) risk of comorbidity and reduction of quality of life due to corticosteroid or other therapies. Methodical guideline focuses on analysis of major statements of these documents, disputable questions of initial therapy choice in patients with pulmonary sarcoidosis.

Sarcoidosis has such characteristics as the high rate of spontanoeus remissions and the potential for relapses. Corticosteroids are still the most common drugs used in the treatment of sarcoidosis. However,the long-term benefits of oral corticosteroid treatment remain controversial. Long-term use may result in many adverse effects. Meanwhile, it is difficult for some patients to taper down or withdraw eorticosteroids. In recent years,there have been studies on examing the role of inhaled corticosteroids. This article summarizes the progress of inhaled corticosteroids in the treatment of pulmonary sarcoidosis. Key words: Sarcoidosis; Corticosteroid ; Inhalation

There is a clinical unmet need to improve treatment for patients with pulmonary sarcoidosis. Both retrospective and prospective drug trials are hampered by the fact that patients with sarcoidosis are characterized by a heterogeneous presentation and disease course. In this review, an overview is given of different drug trials in pulmonary sarcoidosis with an emphasis on different primary endpoints and the problems related to them. In recent years, using significant input from patients with sarcoidosis, different task-forces/studies tried to develop a core set of most important outcomes to measure in future studies on treatment of sarcoidosis. Furthermore, at present, three major clinical trials are being conducted on new drugs for treatment of pulmonary sarcoidosis. Progress has been made to develop a core set of outcomes measures that can be used in making a combined primary endpoint in future drug trials in sarcoidosis.

Conventional treatment of sarcoidosis is often only partially effective. We examined the effect of cyclosporin A (CsA) combined with prednisone for the treatment of sarcoidosis. Thirty-seven patients with biopsy-proven sarcoidosis were treated with either prednisone 20 mg/d in a prospectively tapered regimen (P) or with combination therapy consisting of prednisone 20 mg/d in a prospectively tapered regimen and cyclosporin A, 5 to 7 mg/kg/d (P-CsA) for up to 18 mo in an open-label randomized controlled trial. Evaluation was done at baseline and at 3, 9, and 18 mo of the degree of dyspnea, pulmonary function, chest radiographs, bronchoalveolar lavage (BAL), and adverse events. Criteria for a good therapeutic response, improvement, treatment failure, and relapse were defined. Thirty-seven patients were treated for at least 9 mo and 18 mo. Six patients in remission were included in an intention-to-treat-analysis at 18 mo. The groups did not differ significantly with respect to therapeutic response from baseline. A significant (p < 0.05) improvement was observed in dyspnea until 9 mo (P) and 18 mo (P-CsA), and in lung function until 9 mo (P) and 3 mo (P-CsA). BAL results showed a significant decrease in lymphocyte counts at 9 mo for the P group only (p < 0.05). More side effects were observed in the P-CsA group than in the P group, including elevation of the mean serum creatinine concentration at 3 and 9 mo (p < 0.05), and a doubling of the number of infections in this group. Relapse after an initially good therapeutic response occurred in two of nine patients in the P group and five of seven patients in the P-CsA group (p < 0.07). Although CsA may have theoretical benefits in the treatment of sarcoidosis, our results do not support its use in this disease.

Angiotensin-converting enzyme is used as a marker for sarcoid activity. We describe a case of remission of cutaneous and lymphatic sarcoidosis in a patient treated with an ACE inhibitor for congestive heart failure and hypertension; the remission has continued over 4 years of follow-up. Because this is a report of only one case, there is a possibility of sampling error. Whether the patient's remission in this case was a serendipitous spontaneous remission that happened to occur during ACE inhibitor therapy or whether ACE inhibitor therapy can play a role in the treatment of sarcoidosis needs to be determined in a large clinical trial.

To evaluate the safety and efficacy of minocycline in the treatment of sarcoidosis, a nonrandomized, open study was performed in patients with cutaneous sarcoidosis. Twelve patients with cutaneous sarcoidosis were treated with minocycline, 200 mg/d, for a median duration of 12 months. Three patients had extracutaneous lesions at the time of the study. The median follow-up was 26 months. A clinical response was observed in 10 patients, consisting of complete responses in 8 patients and partial responses in 2 patients. A progression of skin lesions was observed in 1 patient, and lesions remained stable in another patient. Adverse effects were minimal, except in 1 patient, who developed hypersensitivity syndrome. A slight hyperpigmentation occurred in 2 patients at the site of previous lesions, which completely disappeared after minocycline use was discontinued. A relapse of skin symptoms occurred after minocycline withdrawal in 3 patients, who further received doxycycline, 200 mg/d, allowing a complete remission of lesions. These results support that minocycline and doxycycline may be beneficial for the treatment of cutaneous sarcoidosis. Randomized controlled studies are warranted for the evaluation of the true efficacy of tetracyclines in these patients.

Remission of left Tawara-branch block under treatment for systemic sarcoidosis

Clinical Manifestations, Diagnosis, and Treatment of Sarcoidosis

Role of anti-tumor necrosis factor-alpha agents in treatment of sarcoidosis: A meta-analysis

Twenty patients with active sarcoidosis (increased serum ACE activity) and progressive pulmonary disease (stages 2-3) were treated with inhaled budesonide instead of with oral glucocorticosteroids in an open clinical study. Results after an 18-month treatment are reported. A general improvement in chest roentgenograms and FVC was noted. Serum ACE activity was normalized. The results indicate that pulmonary manifestations of sarcoidosis can be treated with the inhaled steroid, budesonide. In this way the risk of systemic side effects is considerably reduced. The final place of inhaled budesonide in the treatment of sarcoidosis must be determined via placebo-controlled and comparative, double-blinded clinical studies in larger series of patients.

Pharmacotherapy for pulmonary sarcoidosis: A delphi consensus study

A double-blind, randomized, placebo-controlled trial of adalimumab in the treatment of cutaneous sarcoidosis

&lt;p&gt;Sarcoidosis is a systemic, multi-organ disease of unknown etiology characteristically defined by the development of non-caseating granulomas. The development of sarcoidosis has been associated with a number of environmental and microbacterial factors coupled with genetic susceptibility. Depending on the type, location and distribution of disease, sarcoidosis can cause functional impairment, symptomatic distress, scarring and disfigurement. The advent of lasers as precise, minimally destructive surgical tools has allowed for their development as promising alternatives that minimize the morbidity associated with current therapies.&lt;/p&gt;&lt;p&gt;In this paper, we reviewed the role of laser therapy in the treatment of cutaneous sarcoidosis. A comprehensive search of the Cochrane Library, MEDLINE and PUBMED databases was performed to identify relevant literatures investigating the role of laser therapy in the treatment of cutaneous sarcoidosis. In our opinion, laser therapy, particularly PDL, appears to be an effective, safe and generally well-tolerated modality for the treatment of cutaneous sarcoidosis and should be considered in patients with localized cutaneous disease that is refractory to conventional treatments. Less is known about the efficacy and tolerability of ablative laser therapy for the treatment of cutaneous sarcoidosis, though the limited data appears promising as well. With that said, however, the data is limited and warrants a need for additional larger, randomized controlled studies to further investigate the utility and efficacy of laser therapy in the treatment of cutaneous sarcoidosis.&lt;/p&gt;

57-Year-Old Man With Hip Pain and Lytic Bone Lesions

Sarcoidosis is an inflammatory multi-systemic disease of unknown origin with wide spectrum of clinical manifestations. Sarcoidosis may affect practically any organ — predominantly lungs, lymphatic system, skin, eyes alone or in combination. The disease is characterized by formation of non-caseous granuloma. In 1999 American Thoracic society (ATS), European Respiratory society (ERS) and World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) adopted an international consensus statement on diagnosis and treatment of sarcoidosis «Statement on Sarcoidosis». Based on ATS, ERS and WASOG 1999 Statement the national documents such as “Evidence-based adapted clinical guideline on sarcoidosis” and “Unified clinical protocol of primary, secondary (specialized) and tertiary (highly-specialized) medical care for sarcoidosis” approved by MOH of Ukraine (decree # 634 dated 08 Sep 2014) were developed by current authors in Ukraine. In 2020 ATS experts published an updated «Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline», according to which the diagnosis of sarcoidosis was based on 3 criteria: compatible clinical symptoms, presence of non-necrotizing granulomatous inflammation in one or more tissue samples (not always required) and exclusion of alternative causes of granulomatous disorder. Finally, in 2021 ERS task force report was published “ERS clinical practice guidelines on treatment of sarcoidosis”, which outlined completely new approaches to management of sarcoidosis patients. According to this document, a decision about treatment of patient depends on 2 major factors: risk of death or organ failure and deterioration of quality of life of a patient. In addition, main principle of management of sarcoidosis patients is a balance between: a) minimization of risk of disability or death due to lung injury and decrease of quality of life, and b) risk of comorbidity and reduction of quality of life due to corticosteroid or other therapies. Current review focuses on analysis of major statements of these documents, disputable questions of initial therapy choice in patients with pulmonary sarcoidosis. Key words: pulmonary sarcoidosis, diagnosis, treatment, glucocorticosteroids, immunosuppressants, cytokine inhibitors.