sildenafil-citrate and Scleroderma--Diffuse

We report a rare case of diffuse systemic sclerosis (SSc) evolving into diffuse SSc/systemic lupus erythematosus (SLE) overlap syndrome. A 15-year-old boy was diagnosed as diffuse SSc with initial presentations of Raynaud's phenomenon and skin tightening. He underwent Chinese herbal treatment and clinical symptoms deteriorated in the following 3 years. On admission to our ward, serositis with pleural effusion, severe pulmonary fibrosis with moderate pulmonary hypertension, swallowing difficulty, and polyarthritis were observed. Autoantibody profiles revealed concurrence of anti-double-stranded DNA, anti-Smith, anti-topoisomerase I, and anti-ribonucleoprotein antibodies. The patient fulfills the criteria for both diffuse SSc and SLE. After drainage for pleural effusion accompanied by oral prednisolone and sildenafil, there were improvement of respiratory distress, swallowing difficulty, and pulmonary hypertension. In conclusion, connective tissue diseases may overlap with each other during the disease course. Serial follow-up for clinical symptoms as well as serological changes is recommended.

Topics: Adolescent; Antihypertensive Agents; Arthritis; Autoantibodies; Biomarkers; Deglutition Disorders; Disease Progression; Drainage; Drugs, Chinese Herbal; Glucocorticoids; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Male; Piperazines; Pleural Effusion; Prednisolone; Pulmonary Fibrosis; Purines; Raynaud Disease; Scleroderma, Diffuse; Serositis; Sildenafil Citrate; Sulfones; Treatment Outcome

Pulmonary hypertension (PH) is an important cause of mortality in systemic sclerosis (SSc), where it can be isolated (pulmonary arterial hypertension [PAH]) or associated with interstitial lung disease (ILD). This study was undertaken to characterize determinants of survival among SSc patients with either type of PH who received PAH-specific therapy.. Consecutive SSc patients with PAH or ILD-associated PH confirmed by right heart catheterization were included in the study. Kaplan-Meier and Cox proportional hazards models were used to compare survival between SSc patients with PAH and those with ILD-associated PH and to identify predictors of survival.. Fifty-nine patients (39 with PAH and 20 with ILD-associated PH) were identified. The majority (15 of 20 with ILD-associated PH and 27 of 39 with PAH) received an endothelin receptor antagonist as initial therapy. Median followup time was 4.4 years (range 2.7-7.4 years). Survival was significantly worse in SSc patients with ILD-associated PH than in those with PAH (1-, 2-, and 3-year survival rates 82%, 46%, and 39% versus 87%, 79%, and 64%, respectively; P < 0.01 by log rank test). In a multivariable analysis, ILD-associated PH was associated with a 5-fold increase in risk of death compared with PAH. Pulmonary vascular resistance index was also an independent predictor of mortality in the overall cohort (hazard ratio 1.05, P < 0.01) and was a significant univariable risk factor in each group separately. Type of initial PAH therapy and the use of warfarin were not related to survival.. Survival in SSc complicated by PH remains poor despite currently available treatment options. While therapy may be associated with improved survival in PAH compared with historical controls, the prognosis for patients with ILD-associated PH is particularly grim. Early diagnosis and treatment may improve outcomes since worsening hemodynamic factors were associated with reduced survival.

Topics: Bosentan; Cohort Studies; Comorbidity; Endothelin Receptor Antagonists; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Isoxazoles; Lung Diseases, Interstitial; Male; Maryland; Middle Aged; Piperazines; Prognosis; Proportional Hazards Models; Purines; Receptors, Endothelin; Scleroderma, Diffuse; Scleroderma, Systemic; Sildenafil Citrate; Sulfonamides; Sulfones; Survival Rate; Thiophenes; Vasodilator Agents

Digital ulcers in progressive systemic sclerosis (PSS) are often refractory to therapy. A frequently chronic aggressive course can lead to the loss of acral limbs involved. A 73-year-old woman developed a dramatic worsening of her ulcerations despite maximum conventional therapy. Switching therapy to bosentan and sildenafil, both in low-dose regimens, resulted for the first time in ten years in a complete healing of the ulcers. If substantiated in a series of patients, the additive and perhaps synergistic clinical benefits of combining bosentan and sildenafil may be a valuable option for the treatment of acral ulcers in PSS.

Topics: Aged; Bosentan; Drug Therapy, Combination; Endothelin Receptor Antagonists; Female; Fingers; Hand Dermatoses; Humans; Phosphodiesterase Inhibitors; Piperazines; Purines; Scleroderma, Diffuse; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Ulcer