Case Report: Afatinib-Induced Interstitial Pneumonia: Experiences and Lessons From Two Patients

Background: Afatinib has shown good efficacy in patients harboring uncommon EGFR mutations, but the incidence of afatinib-induced interstitial pneumonia should be alert as its rapid progression. Here, we report two cases of interstitial pneumonia during afatinib treatment.Case presentation: The first case was of a 58-year-old male with advanced lung adenocarcinoma (cT4bN3M1b) with exon 18 G719X and exon 20 S781I EGFR mutations and received afatinib therapy. After 68 days of therapy, he developed shortness of breath and fever. Drug-induced pneumonia was not diagnosed timely, the patient received empirical antibiotics and low-dose glucocorticoids. The pulmonary inflammation rapidly progressed and the patient died 15 days after symptom onset. The second case was of a 57-year-old man with stage IV (cT3N3M1b) lung adenocarcinoma with exon 21 L861Q EGFR mutation. He received afatinib as second-line therapy. Fever and shortness of breath occurred 22 days after afatinib therapy, he received empirical antibiotic therapy. Five days later, CT showed aggravated pulmonary inflammation, and afatinib-induced interstitial pneumonia was diagnosed. He received glucocorticoid therapy, and the pneumonia quickly improved.Conclusion: Although the incidence of EGFR-TKI-associated pneumonia is uncommon, high vigilance for drug-induced interstitial pneumonia is necessary during treatment. Early diagnosis and early glucocorticoid therapy could reverse lung injury.

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BRAF-MAD1L1 and BRAF-ZC3H7A: novel gene fusion in Rhabdomyosarcoma and Lung adenocarcinoma

10.21203/rs.3.rs-368083/v1 ◽

2021 ◽

Author(s):

Jiang Da ◽

Hui Jin ◽

Xinliang Zhou ◽

Shaoshuang Fan ◽

Mian Xu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Gene Fusion ◽

Tumor Resection ◽

Kinase Domain ◽

Rapid Progression ◽

First Line ◽

Case Presentation ◽

First Case ◽

Exon 11 ◽

Domain Exon

Abstract Background: Rhabdomyosarcoma (RMS) and lung adenocarcinoma (LADC) epitomizes the success of cancer prevention by the development of conventional therapy, but huge challenges remain in the therapy of advanced diseases.Case presentation: We reported two cases of novel BRAF gene fusion. The first case was a 34-year-old female with RMS harboring a BRAF-MAD1L1 fusion. She suffered tumor resection, recurrence and rapid progression. The second case was a 72-year-old female with LADC harboring a BRAF-ZC3H7A fusion, and she gained rapid progression after receiving a first-line course of chemotherapy.Conclusions: These two BRAF fusions retain the intact BRAF kinase domain (exon 11-18) and showed poor prognosis in RMS and LADC.

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Complete Response to Afatinib of an EGFR Exon 18 delE709_T710insD-Mutated Stage IV Lung Adenocarcinoma

European Journal of Case Reports in Internal Medicine ◽

10.12890/2021_002749 ◽

2021 ◽

Author(s):

Blandine Jelli ◽

Olivier Taton ◽

Nicky D'Haene ◽

Myriam Remmelink ◽

Zita Mekinda

Keyword(s):

Lung Adenocarcinoma ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Stage Iv ◽

Complete Response ◽

Egfr Mutations ◽

First Case ◽

Treatment Interruptions ◽

Patient Prognosis ◽

Lung Adenocarcinomas

Introduction: Epidermal growth factor receptor (EGFR) mutations are frequently found in patients with lung adenocarcinomas, 90% being deletions in exon 19 or point mutation in exon 21. Three generations of tyrosine kinase inhibitors (TKIs) targeting EGFR mutations are available and have changed patient prognosis but less data is available on exon 18 mutations and their sensitivity to TKI therapy. Exon 18 delE709_T710insD accounts for 0.06% (16/27,294) of all EGFR mutations and is an oncogenic driver. Several partial responses to afatinib have been described. Case description: We report the first case, to the best of our knowledge, of the complete response to afatinib of a 57-year-old patient with stage IV lung adenocarcinoma with a delE709_T710insD mutation in the EGFR gene detected by next-generation sequencing. Oral afatinib was prescribed and despite treatment interruptions and dosage tapering due to cutaneous adverse events, a complete response was achieved 12 months after treatment initiation and is currently maintained at 17 months. Conclusion: When EGFR mutation is suspected, complete DNA sequencing of exons 18 to 21 should be carried out and we suggest that afatinib should be the first-line treatment for exon 18 delE709_T710insD-mutated advanced lung adenocarcinomas.

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Lethal Arrhythmia (Torsade de Pointes) in COVID-19: An Event Synergistically Induced by Viral Associated Cardiac Injury, Hyperinflammatory Response, and Treatment Drug?

Clinical Medicine Insights Case Reports ◽

10.1177/1179547620972397 ◽

2020 ◽

Vol 13 ◽

pp. 117954762097239 ◽

Cited By ~ 1

Author(s):

Nuraini Yasmin Kusumawardhani ◽

Ian Huang ◽

Erwan Martanto ◽

Teddy Arnold Sihite ◽

Eka Surya Nugraha ◽

...

Keyword(s):

Troponin I ◽

Cardiac Injury ◽

Fatal Outcome ◽

Torsade De Pointes ◽

Shortness Of Breath ◽

Drug Induced ◽

First Case ◽

Increased Risk ◽

Lethal Arrhythmia ◽

Malignant Arrhythmias

Arrhythmias in patients with coronavirus disease 2019 (COVID-19) are prevalent and deserve special attention because they are associated with an increased risk of fatal outcome. The mechanism of arrhythmia in COVID-19 remains unclear. Here, we report our first case of confirmed COVID-19 with documented Torsade de Pointes (TdP). A 64-year-old woman, previously healthy, presented to our emergency department with progressive shortness of breath, dry cough, and 1 week of fever. She was treated with chloroquine phosphate, meropenem, and ciprofloxacin. After 5 days of admission, her condition deteriorated and she was admitted to the intensive care unit. The patient had two episodes of malignant arrhythmias within 24 hours. The former was TdP, and the latter was a fatal pulseless ventricular tachycardia that occured even after chloroquine was discontinued. There was evidence of cardiac injury shown by increased serum level of troponin I. We propose a synergistic concept of lethal arrhythmia due to direct severe acute respiratory syndrome coronavirus (SARS-CoV)-2-associated cardiac injury, hyperinflammatory response, and drug-induced arrhythmia.

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Fatal Tumour Lysis Syndrome Induced by Brigatinib in a Lung Adenocarcinoma Patient Treated With Sequential ALK Inhibitors: A Case Report

Frontiers in Pharmacology ◽

10.3389/fphar.2021.809467 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yadong Wang ◽

Tiange Wang ◽

Jianchao Xue ◽

Ziqi Jia ◽

Xinyu Liu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Clinical Manifestations ◽

Sequential Therapy ◽

Tumour Lysis Syndrome ◽

Resistance Mutations ◽

Laboratory Findings ◽

Tumour Lysis ◽

Anaplastic Lymphoma ◽

First Case ◽

Days Of Therapy

Tumour lysis syndrome (TLS) represents a group of fatal metabolic derangements resulting from the rapid breakdown of tumour cells. TLS typically occurs soon after the administration of chemotherapy in haematologic malignancies but is rarely observed in solid tumours. Here, we report a case of brigatinib-induced TLS after treatment with sequential anaplastic lymphoma kinase (ALK) inhibitors in a patient with advanced ALK-rearranged lung adenocarcinoma. The patient was treated sequentially with crizotinib, alectinib, and ensartinib. High-throughput molecular profiling after disease progression indicated that brigatinib may overcome ALK resistance mutations, so the patient was administered brigatinib as the fourth-line treatment. After 22 days of therapy, he developed oliguria, fever, and progressive dyspnoea. Clinical manifestations and laboratory findings met the diagnostic criteria for TLS. The significant decrease in the abundance of ALK mutations in plasma indicated a therapeutic response at the molecular level. Consequently, the diagnosis of brigatinib-induced TLS was established. To the best of our knowledge, this is the first case of TLS induced by sequential targeted therapy in non-small cell lung cancer. With the extensive application of sequential therapy with more potent next-generation targeted therapeutic drugs, special attention should be given to this rare but severe complication.

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Salmonella pneumonia complicated with encysted empyema in an immunocompromised youth: Case report and literature Review

The Journal of Infection in Developing Countries ◽

10.3855/jidc.7069 ◽

2016 ◽

Vol 10 (04) ◽

pp. 437-444 ◽

Cited By ~ 4

Author(s):

Nermin Kamal Saeed

Keyword(s):

Back Pain ◽

Case Report ◽

Pleural Effusion ◽

Literature Review ◽

Salmonella Enterica ◽

Stage Iv ◽

Shortness Of Breath ◽

Salmonella Infections ◽

First Case ◽

Salmonella Enterica Serotype Enteritidis

In this case report we described a Bahraini male patient of twenty years of age, a smoker and diagnosed with stage IV B Hodgkin lymphoma. He presented with fever, nonproductive cough, upper back pain and shortness of breath due to right upper lobe pneumonia with right encysted pleural effusion. Salmonella enterica serotype Enteritidis was isolated from the sputum. He was successfully treated with 2 weeks of ceftriaxone followed by 2 weeks of oral cefixime. This was the first case of encysted empyema caused by Salmonella enterica serotype Enteritidis reported in the Kingdom of Bahrain. The different aspects of pulmonary Salmonella infections were discussed and the literature was reviewed.

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Case report: BRAF-MAD1L1 and BRAF-ZC3H7A: novel gene fusion in Rhabdomyosarcoma and Lung adenocarcinoma

10.21203/rs.3.rs-58002/v1 ◽

2020 ◽

Author(s):

Da Jiang ◽

Hui Jin ◽

Xinliang Zhou ◽

Shaoshuang Fan ◽

Mengping Lei ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Poor Prognosis ◽

Gene Fusion ◽

Tumor Resection ◽

Kinase Domain ◽

Rapid Progression ◽

First Line ◽

First Case ◽

Exon 11 ◽

Domain Exon

Abstract BackgroundRhabdomyosarcoma (RMS) and lung adenocarcinoma (LADC) epitomizes the success of cancer prevention by the development of conventional therapy, but huge challenges remain in the therapy of advanced diseases. Case presentationWe reported two cases of novel BRAF gene fusion. The first case was a 34-year-old female with RMS harboring a BRAF-MAD1L1 fusion. She suffered tumor resection, recurrence and rapid progression. The second case was a 72-year-old female with LADC harboring a BRAF-ZC3H7A fusion, and she gained rapid progression after receiving a first-line course of chemotherapy. ConclusionsThese two BRAF fusions retain the intact BRAF kinase domain (exon 11-18) and showed poor prognosis in RMS and LADC.

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Cardiac tamponade in a patient with stage IV lung adenocarcinoma treated with pembrolizumab

Immunotherapy ◽

10.2217/imt-2019-0067 ◽

2019 ◽

Vol 11 (18) ◽

pp. 1533-1540 ◽

Cited By ~ 1

Author(s):

Abdul Moiz Khan ◽

Ayesha Munir ◽

Vimala Thalody ◽

Mohamed Khalid Munshi ◽

Syed Mehdi

Keyword(s):

Pericardial Effusion ◽

Lung Adenocarcinoma ◽

Cardiac Tamponade ◽

Stage Iv ◽

High Dose ◽

Shortness Of Breath ◽

Pericardial Window ◽

Large Pericardial Effusion ◽

Immune Mediated ◽

Dose Prednisone

Immunotherapy drugs are associated with a multitude of immune-related adverse events. We describe a case of cardiac tamponade in a patient with stage IV lung adenocarcinoma, with almost 100% expression of PDL-1, treated with pembrolizumab. The patient is a 62-year-old male who developed worsening shortness of breath after five cycles of pembrolizumab. He was diagnosed with large pericardial effusion on computed tomography chest. Echocardiogram confirmed tamponade physiology. He was treated with discontinuation of pembrolizumab and urgent pericardial window followed by high dose prednisone with tapering. The patient responded very well to the treatment. We have comprehensively reviewed cases of pericardial effusion secondary to either immune mediated mechanisms or pseudoprogression.

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Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports

BMC Infectious Diseases ◽

10.1186/s12879-021-05982-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Caroline Bartolo ◽

Victoria Hall ◽

N. Deborah Friedman ◽

Chloe Lanyon ◽

Andrew Fuller ◽

...

Keyword(s):

Diabetes Mellitus ◽

Fungal Infections ◽

Case Reports ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Urogenital Tract ◽

Hypoglycemic Agents ◽

Drug Induced ◽

First Case ◽

Increased Risk

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. Case presentations Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. Conclusions Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

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Pustular Rash in Crohn’s Patient on Ustekinumab Raises Concern for Drug-Induced Paradoxical Psoriasis

Case Reports in Gastroenterology ◽

10.1159/000514952 ◽

2021 ◽

pp. 662-666

Author(s):

Mitra Barahimi ◽

Scott Lee ◽

Kindra Clark-Snustad

Keyword(s):

Side Effect ◽

De Novo ◽

Pustular Psoriasis ◽

Initial Weight ◽

Drug Induced ◽

Clinical Recurrence ◽

Potential Side Effect ◽

First Case ◽

Tnf Antagonist ◽

Subcorneal Pustular Dermatosis

We report the case of a 51-year-old male with Crohn’s disease (CD) who developed a reproducible pustular rash after ustekinumab (UST) administration. The patient first presented with a pustular rash on his hands, body, extremities, and scalp starting 5 weeks after his initial weight-based UST induction. The rash resolved spontaneously, then recurred 4 weeks after his first subcutaneous maintenance dose of UST 90 mg. Biopsy of the affected area demonstrated subcorneal pustular dermatosis (SPD). UST was discontinued and the rash resolved. Unfortunately, the patient experienced clinical recurrence of CD, and given prior failure of multiple CD medications, UST was restarted with premedication. Two weeks after UST re-induction, the rash recurred, though less severe. Given improvement in CD symptoms, UST was continued and the rash managed with topical corticosteroids. This is the first case of drug-induced SPD associated with UST. One case report has previously described de novo pustular psoriasis associated with UST in a patient with CD and enteropathic arthritis. Notably, SPD and pustular psoriasis can be histologically indistinguishable. The development of a paradoxical psoriasiform rash is thought to be one of the few dose and duration dependent side effects of TNF-antagonist therapy but has not previously been established as a side effect of UST. This case demonstrates a new potential side effect of UST.

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Decelerated tumor growth due to hypothyroidism with prolongation of survival in a patient with lung adenocarcinoma: a case report

Journal of International Medical Research ◽

10.1177/0300060519885302 ◽

2019 ◽

Vol 48 (3) ◽

pp. 030006051988530

Author(s):

Jia Hou ◽

Shan-Shan Xiong ◽

Zhao-Qi Huang ◽

Xing-Dong Cai

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Tumor Therapy ◽

Stage Iv ◽

Small Cell Lung ◽

Anti Cancer ◽

Advanced Stages

Lung adenocarcinoma is a form of non-small-cell lung cancer with high mortality in the advanced stages, and is one of the most common histological subtypes of lung cancer in most countries. Prognosis of lung adenocarcinoma is generally poor, with a median survival of 4–13 months. We report a case of unusually prolonged survival of a patient with advanced lung adenocarcinoma complicated by hypothyroidism. A 71-year-old man with stage IV lung adenocarcinoma presented with hypothyroidism. Surprisingly, without any anti-tumor and anti-hypothyroidism therapy, he survived this lung cancer for longer than 2.5 years before his last follow-up visit. Patients with advanced lung adenocarcinoma rarely survive for longer than 2 years, even after therapy. We hypothesize that hypothyroidism is the cause for this discrepancy. Thyroid hormones can promote growth of carcinoma. Therefore, hypothyroidism appears to be beneficial to anti-cancer therapy. We believe that hypothyroidism, as an adverse event commonly occurring in anti-tumor therapy (e.g., an immune checkpoint inhibitor), might not be able to be completely eliminated.

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