Piera Fazzi

Pharmacotherapeutic Management of Pulmonary Sarcoidosis

Corticosteroids are the mainstay of treatment for sarcoidosis. Although the indications for medical therapy of sarcoidosis are controversial, standard therapy for symptomatic, progressive disease consists of corticosteroids. The British Thoracic Society concluded, with respect to systemic corticosteroids for the treatment of sarcoidosis, that some patients required no treatment, some required prednisone for control of symptoms, and others, with persistent disease, appeared to benefit from long-term corticosteroid therapy. Inhaled budesonide can be an effective treatment for lung sarcoidosis, with few adverse effects, when used in combination with oral systemic corticosteroids such as deflazacort administered in a tapered regimen for 6 months. A randomized controlled trial has also demonstrated the efficacy of 3 months of treatment with oral prednisolone in a tapered regimen followed by inhaled budesonide for 15 months in patients with early stage pulmonary sarcoidosis.Alternative drugs are required in chronic resistant sarcoidosis and/or in conditions where systemic corticosteroids are contraindicated. Immunosuppressive agents (chlorambucil, cyclophosphamide, methotrexate, cyclosporine, azathioprine), anticytokine agents (thalidomide, pentoxifylline), antimalarials (chloroquine, hydroxychloroquine), melatonin and monoclonal antibody (infliximab) have been used in such situations.Chlorambucil and cyclophosphamide have been used in anecdotal cases of pulmonary sarcoidosis as corticosteroid-sparing agents. However, their toxicity and neoplastic potential recommend prudence in patient selection. A comparison between combination therapy with cyclosporine and prednisone and prednisone alone has shown an increased prevalence of serious adverse effects with combined therapy with no between-group differences in treatment efficacy. The cost and toxicity of cyclosporine limit its use to patients in whom its efficacy has been proven.In patients with chronic or refractory disease, methotrexate, usually administered once a week as a single oral dose for at least 2 years, has resulted in a significant improvement in respiratory function, chest radiographs and extrapulmonary manifestations. In most patients, this treatment enabled discontinuation of corticosteroids.Azathioprine may be effective as a corticosteroid-sparing agent in the long-term treatment of sarcoidosis. The combination of prednisolone and azathioprine over a period of 2 years has induced long-lasting remission in patients with resistant sarcoidosis. Thalidomide at low doses is effective in selected cases of sarcoidosis with cutaneous and mild pulmonary involvement. Pentoxifylline alone or combined with low doses of corticosteroids has achieved significant improvement in respiratory function in patients with pulmonary sarcoidosis. Chloroquine and hydroxychloroquine have been shown to have a specific effect in cutaneous manifestations, neurological involvement and hypercalcemia associated with sarcoidosis. Infliximab has yielded good results in patients with chronic resistant pulmonary and extrapulmonary sarcoidosis resistant to corticosteroid and cytotoxic therapy. The effectiveness of melatonin in cutaneous and pulmonary sarcoidosis has also been confirmed in a single center.

Thalidomide for improving cutaneous and pulmonary sarcoidosis in patients resistant or with contraindications to corticosteroids

BACKGROUND Limited data report thalidomide improves cutaneous sarcoidosis; no benefit has been reported for pulmonary localization. OBJECTIVES To evaluate feasibility and efficacy of prolonged treatment with thalidomide for cutaneous sarcoidosis associated to pulmonary involvement in patients with resistance or contraindications to steroids. METHODS Nineteen patients were treated with thalidomide for 24 months starting with 200 mg/d for first 2 weeks, followed by 100 mg/d for 11 weeks and a maintenance dose of 100mg on alternate days for 35 weeks, and a gradual scaling down until therapy interruption. Criteria of efficacy were: skin score, serum ACE levels (s-ACE), chest X-ray (CXR), lung function tests (LFTs), and diffusing lung capacity for CO (DLCO). The skin score was computed as arithmetic sum of seven score parameters (min: 0, max: 28). RESULTS Skin score significantly decreased (P<0.001). Lower skin scores occurred after 3 and 6 months (P<0.05). s-ACE levels decreased over time at the third month (P<0.001). CXR assessed by radiological stage significantly improved during the first 6 months (P<0.001). DLCO showed a continuous trend of improvement. Minor side effects that have forced the suspension of the drug were drowsiness/sedation (74%), constipation (68%), and weight gain (53%). Deep vein thrombosis of the lower limbs occurred in one patient (who did not drop out the study). Eight patients (42%) abandoned thalidomide for axonal sensitive peripheral neuropathy (PN) between the ninth and the 24th month of treatment. CONCLUSIONS Thalidomide, long-term at mid-low doses, can be considered as an effective therapeutic alternative in chronic sarcoidosis with resistance or contraindications to steroids.

Lung involvement in systemic sclerosis sine scleroderma treated by plasma exchange

Systemic sclerosis sine scleroderma can present in some patients as pulmonary interstitial fibrosis. Until now ten cases with this particular clinical variant, all men, have been reported in the literature. The knowledge of systemic sclerosis sine scleroderma presenting as lung interstitial involvement is important in clinical practice for an early diagnosis and correct therapeutic strategy. This work reports the clinico-serological features of two further cases, one a woman, of systemic sclerosis sine scleroderma with prevalent lung involvement, and describes the effects of therapeutic plasma exchange.

Thyroid uptake of 67Ga-citrate is associated with thyroid autoimmunity and hypothyroidism in patients with sarcoidosis

PurposeTo evaluate the association of gallium-67 (67Ga)-citrate thyroid uptake with the presence of thyroid disorders in patients with sarcoidosis (S patients).MethodsEighty-four S patients were evaluated by a complete thyroid work-up (neck ultrasound, circulating thyroid hormones and anti-thyroid antibodies, fine-needle aspiration).ResultsIn S patients with 67Ga thyroid uptake (respect those without): serum thyroid-stimulating hormone, the titre of anti-thyroid peroxidase (AbTPO) and/or anti-thyroglobulin antibodies (AbTg), and the prevalence of S patients with hypothyroidism or with positive AbTg or AbTPO was significantly higher; a thyroid hypoechoic pattern was more frequent. The prevalence of thyroid nodules was not significantly different between the two groups. Two cases of papillary thyroid cancer were observed in S patients without 67Ga thyroid uptake, whilst no case in those with 67Ga thyroid uptake.Conclusions67Ga thyroid uptake is associated with the presence of aggressive autoimmune thyroiditis and hypothyroidism in S patients; thyroid function and ultrasonography should be performed in the presence of 67Ga thyroid uptake.

Sarcoidosis and Thyroid Autoimmunity

Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb)], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S). A significantly higher prevalence of clinical hypothyroidism and Graves’ disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67) scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid) should have periodically thyroid function evaluations and suitable treatments.

A Comparison of the Ability of Different Lung Function Tests to Discriminate Asymptomatic Smokers and Non-Smokers

We studied 120 volunteers, 20 to 49 year old, equally divided into sex and smoking habit groups to assess the ability of lung function tests to discriminate smokers from non smokers. The subjects performed routine spirometry including helium dilution, body plethysmography, single breath nitrogen test and forced expiratory manoeuvre. Admission criteria were: 1) normal chest x-ray, 2) absence of cardiorespiratory diseases, 3) absence of repiratory symptoms and exposures (by a questionnaire), 4) normal routine spirometry, and 5) FEV1/VC% > 70. The F-value was calculated for the difference between means in smokers and non-smokers, adjusted for age and height by covariance analysis on transformed variables. Results showed that CV, CV/VC%, N2%1, FEF75-85 and Vmax75 had the highest ability to discriminate smokers and non smokers both in males and females. Other tests, such as plethysmography and helium dilution, were not sensitive. A ranking approach, with the determination of percentage of misclassification for each test using a statistical method, confirmed this trend for both sexes. Assumptions of Gaussian distribution, use of equations based on other population, and use of arbitrary criteria of abnormality were thus avoided.

Automatic Computation of Single Breath Nitrogen Test

Single breath nitrogen test (SBN) provides a considerable amount of information about different indices of lung function:1 closing volume (CV), slope of alveolar plateau (ΔN2%lt), total lung capacity (TLC) and derived indexes (functional residual capacity and residual volume). CV and ΔN2%lt are considered suitable to detect early stages of airways obstruction. Thus they have been proposed for epidemiological studies.