Medication-associated gastrointestinal tract injury.

Virchows Arch. 2017 Mar;470(3):245-266

Authors: Vieth M, Montgomery E

Abstract
Medication-associated gastrointestinal (GI) tract injury has been known for centuries for some medications. The more recently introduced biologicals are a class of drugs that constantly increases, and as such, the spectrum of GI tract side effects is steadily growing. This review covers not only long-known GI tract side effects of drugs but also those more recently described. A comprehensive but concise list of medications used in daily practice and associated with GI tract injury is presented.

PMID: 28133700 [PubMed - indexed for MEDLINE]

Recent Advances in Assessing Immunogenicity of Therapeutic Proteins: Impact on Biotherapeutic Development.

J Immunol Res. 2016;2016:8141269

Authors: Lu Y, Khawli LA, Purushothama S, Theil FP, Partridge MA

PMID: 27642612 [PubMed - indexed for MEDLINE]

SEC Based Method for Size Determination of Immune Complexes of Therapeutic Antibodies in Animal Matrix.

J Immunol Res. 2016;2016:9096059

Authors: Boysen M, Schlicksupp L, Dreher I, Loebbert R, Richter M

Abstract
Therapeutic monoclonal antibodies (mAbs) represent a milestone in pharmacological development. Their superiority is based on the combination of high specificity, low toxicity, and long half-life that characterizes biologics. If biologics have Achilles' heel, it is their potential immunogenicity. To better understand the impact of the size of immune complexes of mAbs on anti-drug antibody (ADA) dependent adverse reactions in Macaca fascicularis, we developed an efficient high-throughput size exclusion chromatography- (SEC-) based methodology that enables analysis of the size, size distribution, and ratio of free and ADA-complexed mAb in serum allowing for assessment of formation and clearance of circulating ADA-mAb immune complexes (CIC).

PMID: 27556050 [PubMed - indexed for MEDLINE]

Predictive models of cytotoxicity as mediated by exposure to chemicals or drugs.

SAR QSAR Environ Res. 2016 Jun;27(6):455-68

Authors: Moon H, Cong M

Abstract
Predicting cytotoxicity is a challenging task because of the complex biological mechanisms behind it. Cytotoxicity due to toxin - biologically produced poison - is known to play a substantial role in a disease process. Two objectives in this research are to derive robust general predictive cytotoxicity models to minimize unnecessary toxicity. The first objective is to build accurate predictive statistical models for cytotoxicity data based on lymphoblastoid cell lines obtained from in vitro studies. This could be an important step for accomplishing a goal in biomedecial/biophamarceutical research, by obtaining the best medical outcomes by minimizing toxicity in regard to a person's genetic profile. The second objective is to build predictive models to predict population-level cytotoxicity for unknown compounds based on chemical structural features. These two objectives were accomplished by a proposed variable selection process, the random forests, and the least absolute shrinkage and selection operator method. We achieved an excellent prediction result with the random forests algorithm using SNP markers from the proposed approach, having the smallest root mean squared error among the teams which participated in the DREAM Toxicogenetics Challenge. Since chemical compounds for drugs have great influence on human health, the predictive statistical models for these objectives could be helpful to government agencies in relevant decision-making.

PMID: 27442234 [PubMed - indexed for MEDLINE]

A review of adverse events caused by immune checkpoint inhibitors.

Nihon Rinsho Meneki Gakkai Kaishi. 2016;39(1):30-6

Authors: Fukushima S

Abstract
  There has been no effective therapy in the unresectable melanoma for more than 40 years. Anti-PD-1 antibody and anti-CTLA-4 antibody have totally changed the situation. They have clearly shown the survival benefits of the patients with metastatic melanoma. However, immune checkpoint inhibitors sometimes induce various kinds of immune-related adverse events (irAEs). It is very important for the clinicians to know the reported cases of irAEs and to keep in mind the symptoms of irAEs for the early detection. This review describes the previously reported irAEs and adequate managements for irAEs induced by immune checkpoint inhibitors.

PMID: 27181232 [PubMed - indexed for MEDLINE]

Dosing recommendations for pharmacogenetic interactions related to drug metabolism.

Pharmacogenet Genomics. 2016 07;26(7):334-9

Authors: Filipski KK, Pacanowski MA, Ramamoorthy A, Feero WG, Freedman AN

Abstract
OBJECTIVE: Pharmacogenomic studies have established the important contribution of drug-metabolizing enzyme genotype toward drug toxicity and treatment failure; however, clinical implementation of pharmacogenomics has been slow. The aim of this study was to systematically review the information on drug-metabolizing enzyme pharmacogenomics available in the US drug labeling, practice guidelines, and recommendations.
METHODS: Drug-metabolizing enzyme genotype and phenotype information was assessed in US FDA drug labeling, clinical practice guidelines, and independent technology assessors to evaluate the consistency in information sources for healthcare providers.
RESULTS: Eighty four gene-drug pairs were identified as having drug-metabolizing enzyme genotype or phenotype information within the label. The manner in which pharmacogenomic information was presented was heterogeneous both within the label and between clinical practice recommendations.
CONCLUSION: For proper implementation of pharmacogenomics in clinical practice, information sources for healthcare providers should relay consistent and clear information for the appropriate use of biomarkers.

PMID: 27058883 [PubMed - indexed for MEDLINE]

Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical trial cohort.

Regul Toxicol Pharmacol. 2016 Jun;77:257-62

Authors: Shantakumar S, Landis S, Lawton A, Hunt CM

Abstract
Few epidemiologic studies describe longitudinal liver chemistry (LC) elevations in cancer patients. A population-based retrospective cohort was identified from 31 Phase 2-3 oncology trials (excluding targeted therapies) conducted from 1985 to 2005 to evaluate background rates of LC elevations in patients (n = 3998) with or without liver metastases. Patients with baseline liver metastases (29% of patients) presented with a 3% prevalence of alanine transaminase (ALT) ≥ 3x upper limits normal (ULN) and 0.2% prevalence of bilirubin ≥ 3xULN. During follow-up, the incidence (per 1000 person-months) of new onset ALT elevations ≥3xULN was 6.1 (95% CI: 4.5, 8.0) and 2.2 (95% CI: 0.9, 4.5) in patients without and with liver metastases, respectively. No new incident cases of ALT and bilirubin elevations suggestive of severe liver injury occurred among those with liver metastases; a single case occurred among those without metastasis. Regardless of the presence of liver metastases, LC elevations were rare in cancer patients during oncology trials, which may be due to enrollment criteria. Our study validates uniform thresholds for detection of LC elevations in oncology studies and serves as an empirical referent point for comparing liver enzyme abnormalities in oncology trials of novel targeted therapies. These data support uniform LC stopping criteria in oncology trials.

PMID: 27025923 [PubMed - indexed for MEDLINE]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/03/16

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Dysregulation of BET proteins in levodopa-induced dyskinesia.

Neurobiol Dis. 2017 Mar 09;:

Authors: Figge D, Standaert DG

Abstract
Levodopa (L-DOPA) remains the most effective pharmacological treatment for Parkinson's Disease (PD) but its use is limited by the development of debilitating drug-related side effects, particularly L-DOPA induced dyskinesia (LID). LID is a consequence of long-term L-DOPA use, and in model systems is characterized by a "priming effect", whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent dopaminergic stimulation. Preliminary studies into the mechanisms underlying this cellular memory have indicated an important role for epigenetic change but many of the downstream mechanisms remain unknown. The family of bromodomain and extraterminal (BET) proteins, which bind acetylated histones, play a critical effector role in the regulation of transcription. BET proteins have been implicated in several forms of neural plasticity, but their potential relevance to LID remains unexplored. Using the 6-OHDA rodent model of LID, we show that dyskinesia development induces alterations in BET protein expression along with enhanced occupation of sites at the promoter and enhancer regions of genes dysregulated during dyskinesia development. When BET function was blocked using the pharmacologic inhibitor JQ1, LID was prevented. In addition, we found that JQ1 treatment blocked the transcriptional upregulation of several immediate-early genes known to participate in the pathogenesis of dyskinesia. Together, these results demonstrate an essential role for BET protein activity as an epigenetic "reader" of the altered histone acetylation required for LID development and suggest that modulation of BET protein function is a potential therapeutic avenue for the treatment prevention or reversal of LID in PD.

PMID: 28286180 [PubMed - as supplied by publisher]

The insect repellents: A silent environmental chemical toxicant to the health.

Environ Toxicol Pharmacol. 2017 Mar;50:91-102

Authors: Roy DN, Goswami R, Pal A

Abstract
In recent years, a large number of insect repellents have been developed with the idea of consumer benefits. In addition to already known advantageous application of insect repellents, there is increasing concern about the potential toxicity in environment leading to health caused by random use of these compounds. An increasing number of evidence suggests that insect repellents may trigger undesirable hazardous interactions with biological systems with a potential to generate harmful effects including intermediate metabolites. Biotransformation followed by bioaccumulation (vice e versa) may be an important phenomenon for toxic response of this chemicals. In this review, we have summarized the current state of knowledge on the insect repellent toxicity, including biochemical pathway alteration under in vitro and in vivo conditions considering different classes of organisms, from lower to higher vertebrate. Furthermore, we have tried to incorporate the effects of insect repellent in light of some clinical reports. We hope this review would provide useful information on potential side effects of uncontrolled use of insect repellents.

PMID: 28171823 [PubMed - indexed for MEDLINE]

Antimalarial activity of the terpene nerolidol.

Int J Antimicrob Agents. 2016 Dec;48(6):641-646

Authors: Saito AY, Marin Rodriguez AA, Menchaca Vega DS, Sussmann RA, Kimura EA, Katzin AM

Abstract
Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent. In this study, the antimalarial activity of nerolidol was investigated in a mouse model of malaria. Mice were infected with Plasmodium berghei ANKA and were treated with 1000 mg/kg/dose nerolidol in two doses delivered by the oral or inhalation route. In mice treated with nerolidol, parasitaemia was inhibited by >99% (oral) and >80% (inhalation) until 14 days after infection (P <0.0001). On Day 30 post-infection, the survival rate of orally treated mice was 90% compared with 16% in controls (P <0.0001). In contrast, inhalation-treated mice showed a survival rate of 50% vs. 42% in controls (P > 0.05). The toxicity of nerolidol administered by either route was not significant, whilst genotoxicity was observed only at the highest dose tested. These results indicate that combined use of nerolidol and other drugs targeting different points of the same isoprenoid pathway may be an effective treatment for malaria.

PMID: 27742206 [PubMed - indexed for MEDLINE]

Assessing Natural Product-Drug Interactions: An End-to-End Safety Framework.

Regul Toxicol Pharmacol. 2016 Apr;76:1-6

Authors: Roe AL, Paine MF, Gurley BJ, Brouwer KR, Jordan S, Griffiths JC

Abstract
The use of natural products (NPs), including herbal medicines and other dietary supplements, by North Americans continues to increase across all age groups. This population has access to conventional medications, with significant polypharmacy observed in older adults. Thus, the safety of the interactions between multi-ingredient NPs and drugs is a topic of paramount importance. Considerations such as history of safe use, literature data from animal toxicity and human clinical studies, and NP constituent characterization would provide guidance on whether to assess NP-drug interactions experimentally. The literature is replete with reports of various NP extracts and constituents as potent inhibitors of drug metabolizing enzymes, and transporters. However, without standard methods for NP characterization or in vitro testing, extrapolating these reports to clinically-relevant NP-drug interactions is difficult. This lack of a clear definition of risk precludes clinicians and consumers from making informed decisions about the safety of taking NPs with conventional medications. A framework is needed that describes an integrated robust approach for assessing NP-drug interactions; and, translation of the data into formulation alterations, dose adjustment, labelling, and/or post-marketing surveillance strategies. A session was held at the 41st Annual Summer Meeting of the Toxicology Forum in Colorado Springs, CO, to highlight the challenges and critical components that should be included in a framework approach.

PMID: 26776752 [PubMed - indexed for MEDLINE]

Adverse outcome pathways: From research to regulation scientific workshop report.

Regul Toxicol Pharmacol. 2016 Apr;76:39-50

Authors: Kleinstreuer NC, Sullivan K, Allen D, Edwards S, Mendrick DL, Embry M, Matheson J, Rowlands JC, Munn S, Maull E, Casey W

Abstract
An adverse outcome pathway (AOP) helps to organize existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop in Bethesda, Maryland considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop.

PMID: 26774756 [PubMed - indexed for MEDLINE]

Defibrotide for Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS): Interim Results From a Treatment IND Study.

Biol Blood Marrow Transplant. 2017 Mar 08;:

Authors: Richardson PG, Smith AR, Triplett BM, Kernan NA, Grupp SA, Antin JH, Lehmann L, Shore T, Iacobelli M, Miloslavsky M, Hume R, Hannah AL, Nejadnik B, Soiffer RJ, Defibrotide Study Group

Abstract
Hepatic veno-occlusive disease, or sinusoidal obstruction syndrome (VOD/SOS), is a serious and potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) or of chemotherapy regimens alone. Defibrotide is a complex mixture of single-stranded polydeoxyribonucleotides that is approved in the United States for treatment of hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT and in the European Union, Israel, and South Korea for treatment of severe hepatic VOD/SOS post-HSCT. Defibrotide was previously available in the United States as an investigational drug through a treatment protocol (treatment IND) study. Interim results of that large, treatment IND study of patients with VOD/SOS and with or without multi-organ dysfunction (MOD, also known as multi-organ failure) are presented here. Defibrotide was administered intravenously at 6.25 mg/kg every 6 hours (25 mg/kg/day), with a recommended treatment duration of at least 21 days. Enrolled patients (N=681) were diagnosed with VOD/SOS according to Baltimore or modified Seattle criteria or liver biopsy. For patients who had received HSCT (n=573), 50.3% (n=288; 95% confidence interval [CI], 46.2% to 54.4%) were alive at day +100 post-HSCT. Day +100 survival for the pediatric (≤16 years) and adult (>16 years) subgroups was 54.5% (n=174/319; 95% CI, 49.1% to 60.0%) and 44.9% (n=114/254; 95% CI, 38.8% to 51.0%), respectively. In the MOD subgroup (n=351), 45.3% (n=159; 95% CI, 40.1% to 50.5%) of patients were alive at day +100 post-HSCT. Treatment with defibrotide was generally well tolerated, and drug-related toxicities were consistent with prior studies. Adverse events were reported in 69.6% (399/573) of safety-evaluable patients. Other than VOD/SOS and associated MOD symptoms, the most commonly reported treatment-emergent adverse event was hypotension (13.8%). Day +100 survival results observed in this trial were consistent with results seen in previous trials of defibrotide for VOD/SOS in adult and pediatric patients. These data support the potential benefit of defibrotide in treating a VOD/SOS patient population that includes those with or without MOD.

PMID: 28285079 [PubMed - as supplied by publisher]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/03/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line nonsquamous non-small cell lung cancer studies.

Curr Med Res Opin. 2017 Feb 20;:1-11

Authors: Okamoto I, Schuette WH, Stinchcombe TE, Rodrigues-Pereira J, San Antonio B, Chen J, Liu J, John WJ, Zinner RG

Abstract
OBJECTIVES: This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min·mL (PCb5) or 6 mg/min·mL (PCb6), two widely used regimens in clinical practice for advanced nonsquamous non-small cell lung cancer.
METHODS: All patients received pemetrexed 500 mg/m(2) every 21 days with either of two carboplatin doses for up to 4 to 6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized.
RESULTS: A total of 486 patients mainly from the United States, Europe, and East Asia were included in the analysis; 22% (N = 105) received PCb5 in one trial and 78% (N = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 versus PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses.
CONCLUSIONS: Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, our results show that the PCb5 regimen was generally associated with a better safety profile than PCb6 across three statistical approaches, with no apparent impact on survival outcomes.

PMID: 28277871 [PubMed - as supplied by publisher]

How I manage the toxicities of myeloma drugs.

Blood. 2017 Mar 08;:

Authors: Delforge M, Ludwig H

Abstract
The treatment of multiple myeloma is considered a continuously evolving paradigm as a result of the growing availability of new and highly effective drugs, including first-and second-generation proteasome inhibitors, immunomodulatory agents and monoclonal antibodies. Clinical trials advocate long-term rather than short-term treatment schedules with combinations of these new anti-myeloma drug classes. Although the overall toxicity profile of the recommended regimens can be considered favorable, their increasing complexity and prolonged use warrants a heightened vigilance for early and late side-effects, a priori because real-life patients can be more frail or present with one or more comorbidities. The treatment decision process -at diagnosis and at relapse- therefore requires myeloma physicians to carefully balance efficacy and toxicity profiles for each individual patient. Early and/or unneccesary tapering or treatment discontinuation for drug-related adverse events may not only reduce patients their quality of life, but can also negatively impact their outcome. Accurate knowledge in recognizing and managing the potential side-effects of present-day treatment regimens is therefore a cornerstone in myeloma care. Using 5 case vignettes, we discuss how to prevent and manage the most common non-hematological adverse events of anti-myeloma treatment regimens containing proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies.

PMID: 28275090 [PubMed - as supplied by publisher]

Long-term safety and efficacy of combined tiotropium and olodaterol in Japanese patients with chronic obstructive pulmonary disease.

Respir Investig. 2017 Mar;55(2):121-129

Authors: Ichinose M, Kato M, Takizawa A, Sakamoto W, Grönke L, Tetzlaff K, Fukuchi Y

Abstract
BACKGROUND: The efficacy and safety of once-daily tiotropium+olodaterol (T+O) (2.5/5µg or 5/5µg) for treating chronic obstructive pulmonary disease (COPD) have been demonstrated in the large, multinational, randomized, Phase III studies TONADO(®) 1 and 2, which included 413 Japanese patients (~80 in each group). This study was conducted to supplement the TONADO(®) study data to assess long-term safety in ≥100 Japanese patients treated for 1 year in compliance with International Conference on Harmonisation guidelines. Efficacy was evaluated descriptively as a secondary end point.
METHODS: Patients were randomized to 52 weeks of double-blind treatment with once-daily T+O (2.5/5 or 5/5µg) or O (5µg) monotherapy via the Respimat(®) inhaler. We report the safety and efficacy data descriptively.
RESULTS: The incidence of adverse events (AEs) was comparable in the T+O 2.5/5µg (75.0%), T+O 5/5µg (85.4%), and O 5µg (80.5%) groups, with drug-related AEs being reported in 5.0%, 7.3%, and 4.9% of patients, respectively. Serious AEs were reported in 14 patients (11.5%). The change from baseline in forced expiratory volume in 1s (FEV1) area under the curve from 0 to 3h and trough FEV1 were numerically higher in the T+O treatment groups than in the O monotherapy group throughout the study period. Overall safety of T+O was comparable to that in the TONADO(®) studies.
CONCLUSIONS: No safety concerns for long-term T+O treatment were identified in Japanese patients with COPD. A numerical improvement in lung function was observed with T+O treatment compared to O monotherapy.

PMID: 28274527 [PubMed - in process]

Liver Effects of Clinical Drugs Differentiated in Human Liver Slices.

Int J Mol Sci. 2017 Mar 07;18(3):

Authors: Vickers AE, Ulyanov AV, Fisher RL

Abstract
Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM), diclofenac (DCF, 1 mM) and etomoxir (ETM, 100 μM). Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM) and cyclosporin A (CSA, 10 μM), while GSH was affected more than ATP by methimazole (MMI, 500 μM), terbinafine (TBF, 100 μM), and carbamazepine (CBZ 100 μM). Oxidative stress genes were affected by TBF (18%), CBZ, APAP, and ETM (12%-11%), and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%-6%). Apoptosis genes were affected by DCF (14%), while apoptosis plus necrosis were altered by APAP and ETM (15%). Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%), ETM (66%), DCF, TBF, MMI (61%-60%), APAP, CBZ (57%-56%), and DTL (48%). Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%), CBZ and ETM (44%-43%), APAP and DCF (40%-38%), MMI, TBF and CSA (37%-35%). This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

PMID: 28272341 [PubMed - in process]

Sarcoidosis associated with infliximab therapy in ulcerative colitis: A case report.

Medicine (Baltimore). 2017 Mar;96(10):e6156

Authors: Gîlcă GE, Diaconescu S, Bălan GG, Timofte O, Ştefănescu G

Abstract
RATIONALE: Although immunomodulatory therapy has been clearly stated as an important landmark in treatment of ulcerative colitis, significantly improving the quality of life for patients with inflammatory bowel disease, there are several aspects to be considered regarding the possible side-effects of anti-TNF alpha agents. In spite of a good safety profile, biologic TNF antagonists may induce paradoxical inflammation, which can manifest as sarcoid-like granulomatosis, consisting of noncaseating granulomas in the affected organs.
PATIENT CONCERNS: We report the case of a 30-year-old male patient, with no personal or familial history of lung disease, with a personal history of ulcerative colitis (UC), under clinical remission following infliximab therapy in maintenance dose, who was admitted for treatment administration, but also for dyspnea, nocturnal sweating, and nonproductive cough.
DIAGNOSES: Based on clinical manifestations, biological landmarks excluding various infections, CT scan, fibrobronchoscopy with bronchoalveolar lavage for culture and immunohistochemical examination, followed by mediastinoscopy with sampling of paratracheal lymph node, which underwent histopathological examination, the patient was diagnosed with drug- induced stage II pulmonary sarcoidosis.
INTERVENTIONS: Since the patient had developed severe allergic reaction after being administered Infliximab at admission, the biological treatment was immediately discontinued. Following the diagnosis of pulmonary sarcoidosis, corticotherapy was initiated.
PATIENT OUTCOMES: After corticotherapy was initiated, the patient had a favorable outcome at 3 months reevaluation, both regarding the course of ulcerative colitis and sarcoidosis.
LESSONS: Patients under biological therapy using anti-TNF alpha agents must be carefully monitored, in order to early identify potential paradoxical inflammation (such as sarcoidosis) as a side-effect. The drug-related pulmonary disease tends to improve upon withdrawal of the drug, with occasional requirement of steroid treatment. However, a thorough strategy should be assembled in the case of UC relapse in this patient category, with switching to adalimumab or surgical approach as main possibilities.

PMID: 28272203 [PubMed - in process]