Multiple drugs

Abstract

Various toxicities: 7 case reports In a retrospective study of 11 patients who had been treated at an institute in Poland between 2012 and 2019 for primary immunodeficiencies (PID)related interstitial lung disease (ILD), 7 males aged 5–19 years were described, who developed Cushing syndrome, pancreatitis, osteoporosis, fractures, hepatitis, liver injury, cholestasis, steroid dependence, leucopenia, hypertransaminasaemia or depression during treatment with azathioprine, dexamethasone, methylprednisolone, mycophenolatemofetil, prednisone or sirolimus for PIDrelated ILD [not all routes and outcomes stated; times to reactions onsets not stated]. A 13-year-old boy (patient 1 from table 3 of the article): The boy, who had PID-related ILD, presented with symptoms of splenomegaly and thrombocytopenia. Investigations revealed common variable immunodeficiency (CVID) and lung biopsy showed granulomatous-lymphocytic interstitial lung disease (GLILD)/lymphocytic interstitial pneumonia (LIP). He started receiving immunosuppressive regimen comprising dexamethasone 1.0 mg/kg (scheduled for 10 days), prednisone with initial dose of 1.0 mg/kg, followed by a maintenance dose of 0.2 mg/kg. Following the treatment, a clinical and radiological improvement was noted. However, the residual lesions in the lung persisted. He developed steroid-related Cushing syndrome, and was therefore switched to azathioprine 2 mg/kg. Clinical stabilisation was achieved; however, he developed azathioprine-induced pancreatitis. Therefore, he was transitioned to mycophenolate-mofetil 500 mg/day. The pancreatitis resolved after discontinuation of azathioprine treatment. However, mycophenolate-mofetil was found to be ineffective, and a clinical and radiological progression and progression of lung infiltrates were noted. The symptoms splenomegaly, leucopenia and hypogammaglobulinaemia persisted during treatment with unspecified steroids and mycophenolate-mofetil. Thereafter, he underwent haematopoietic stem cell transplantation (HSCT) and developed infectious complications after HSCT. He also underwent splenectomy due to refractory thrombocytopenia. Later, a clinical and radiological improvement was noted. He concomitantly received unspecified immunoglobulin replacement therapy (IgRT) during the study. A 13-year-old boy (patient 3 from table 3 of the article): The boy, who had PID-related ILD, presented with symptoms of dyspnoea, crackles and acute respiratory failure. Investigations revealed common variable immunodeficiency (CVID) and lung biopsy showed granulomatous-lymphocytic interstitial lung disease (GLILD). He started receiving immunosuppressive regimen comprising IV methylprednisolone 30 mg/kg pulses for 3 days and prednisone with initial dose of 2.0 mg/kg, followed by maintenance dose of 0.4 mg/kg. Following the treatment, a resolution of respiratory failure, incomplete radiological (partial resolution of nodular lesions) and clinical (exercise intolerance) improvement was noted. However, he developed treatment complications in the form of Cushing syndrome and osteoporosis with multiple compression fractures of lumbar vertebrae. Radiological and clinical deterioration was observed while reducing the steroid dose. Therefore, he started receiving azathioprine 2.0–3.5 mg/kg [sic] and a significant clinical and radiological improvement was noted. However, he developed azathioprine-related hepatitis with liver injury and cholestasis. Therefore, the dose of azathioprine was modified depending on the 6-thioguanine levels and due to the adverse effects, azathioprine was later discontinued. The liver injury and cholestasis resolved after azathioprine discontinuation. He concomitantly received unspecified immunoglobulin replacement therapy (IgRT) during the study. A 19-year-old man (patient 4 from table 3 of the article): The man, who had PID-related ILD, presented with symptoms of generalised lymphadenopathy. Investigations revealed common variable immunodeficiency (CVID) and lung biopsy showed granulomatous-lymphocytic interstitial lung disease (GLILD)/lymphocytic interstitial pneumonia (LIP). He started receiving immunosuppressive regimen comprising prednisone with initial dose of 2.0 mg/kg, followed by maintenance dose of 0.6 mg/kg. The clinical symptoms resolved and partial radiological improvement was noted. However, he developed treatment complication in the form of Cushing syndrome. Recurrence of radiological changes were observed while discontinuing the prednisone. He concomitantly received unspecified immunoglobulin replacement therapy (IgRT) during the study. A 5-year-old boy (patient 5 from table 3 of the article): The boy, who had PID-related ILD, presented with symptoms of skin nodules, generalised lymphadenopathy, hepatosplenomegaly and pancytopenia. Investigations revealed mutation in the lipopolysaccharide-responsive and beige-like anchor protein (LRBA) gene and lung biopsy showed granulomatous-lymphocytic interstitial lung disease (GLILD)/lymphocytic interstitial pneumonia (LIP). He started receiving immunosuppressive regimen comprising prednisone with initial dose of 2.0 mg/kg, followed by maintenance treatment with methylprednisolone 0.1 mg/kg in tapered doses. Following the treatment, almost total resolution of radiological changes were noted. He developed severe steroiddependent thrombocytopenia. He thus started receiving mycophenolate-mofetil 400 mg/day almost simultaneously with prednisone. A Subsequent improvement in radiological changes was evident. Due to thrombocytopenia, mycophenolate-mofetil was replaced with sirolimus [rapamycin] 1.6–1.4 mg/kg [sic]; however, he developed treatment complication in the form of transient leucopenia and hypertransaminasaemia. He concomitantly received unspecified immunoglobulin replacement therapy (IgRT) during the study. A 16-year-old boy (patient 6 from table 3 of the article): The boy, who had PID-related ILD, presented with symptoms of hepatosplenomegaly, anaemia and lymphadenopathy. Investigations revealed common variable immunodeficiency (CVID) and lung biopsy showed granulomatous-lymphocytic interstitial lung disease (GLILD). He started receiving immunosuppressive regimen comprising prednisone with initial dose of 0.7 mg/kg, followed by maintenance dose of 0.5 mg/kg. Haematological improvement after 3 months was achieved, without resolution of radiological findings. However, he developed treatment complication in the form of Cushing syndrome and depression. He also reported periodically a subjective feeling of dyspnoea. He concomitantly received unspecified immunoglobulin replacement therapy (IgRT) during the study. A 10-year-old boy (patient 7 from table 3 of the article): The boy, who had PID-related ILD, presented with symptoms of dyspnoea, crackles and acute respiratory failure. Investigations revealed common variable immunodeficiency (CVID) and lung biopsy showed granulomatous-lymphocytic interstitial lung disease (GLILD)/lymphocytic interstitial pneumonia (LIP). He started receiving immunosuppressive regimen comprising prednisone with initial dose of 2.0 mg/kg, followed by maintenance dose of 0.2 mg/kg. A significant clinical and radiological improvement was noted. However, he developed treatment complication in the form of Cushing syndrome. He concomitantly received unspecified immunoglobulin replacement therapy (IgRT) during the study. A 12-year-old boy (patient 8 from table 3 of the article): The boy, who had PID-related ILD, presented with symptoms of severe viral enterocolitis, facial dysmorphia, parakeratosis, hydrocephalus, hypospadias, strabismus and cryptorchidism. Investigations revealed with Nijmegen breakage syndrome (NBS) and lung biopsy showed granulomas. He started receiving immunosuppressive regimen comprising prednisone with initial dose of 1.0 mg/kg, followed by maintenance dose of 0.2 mg/kg. Clinical and radiological improvement was noted. However, he developed treatment complication in the form of Cushing syndrome. He was then treated with ciclosporin and clinical stabilisation was achieved. He concomitantly received unspecified immunoglobulin replacement therapy (IgRT) during the study. 1