---
title: "Immune checkpoint inhibitor–related multi-organ injury with severe pneumonia: case report (Frontie"
id: "frontiers-in-immunology-16-immune-checkpoint-inhibitor-induced-multi-organ-immune-damage-complicated-by"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-16-immune-checkpoint-inhibitor-induced-multi-organ-immune-damage-complicated-by"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.2003924"
published_at: "2026-10-21T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Immune checkpoint inhibitor–related multi-organ injury with severe pneumonia: case report (Frontie
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-16-immune-checkpoint-inhibitor-induced-multi-organ-immune-damage-complicated-by
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.2003924)
- **Published At:** 2026-10-21T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The published item is a CASE REPORT listed on Frontiers in Immunology with the title indicating **immune checkpoint inhibitor**–induced **multi-organ** immune damage complicated by **severe pneumonia**. The article metadata appears on the journal site, but the provided source text did not include the case narrative, patient data, or results. - The source did not supply patient demographics, cancer type, or the specific immune checkpoint inhibitor agent involved; such details were not present in the accessible text. - No information about timing of onset, clinical signs, laboratory results, imaging findings, or organ-specific involvement was available in the provided source content. - The source text contained no treatment details: dosing, immunosuppressive therapy (for example corticosteroids), antimicrobial therapy, mechanical ventilation, or other supportive measures were not reported in the supplied excerpt. - The report did not include defined endpoints, outcomes, follow-up duration, or pathology/autopsy findings in the text provided here. Those methodological and outcome data were absent. - No microbiology, pathogen identification, or evidence distinguishing infectious pneumonia from immune-related pneumonitis was present in the source excerpt. The distinction therefore cannot be confirmed from the available text. - Authors, institutional affiliations, case timeline, and consent/ethics information were not available in the extracted content. These elements were not reported in the provided source material. - Because the source text lacks case detail, clinicians should consult the original Frontiers in Immunology article URL for the complete clinical narrative and data before applying observations to practice; the excerpt here is insufficient for clinical decision-making.
## Clinical Analysis & Structured Key Points
Frontiers | Immune checkpoint inhibitor-induced multi-organ immune damage complicated by severe pneumonia: case report CASE REPORT article Front. Immunol. , 21 October 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.2003924 Published in Frontiers in Immunology Cancer Immunity and Immunotherapy 7 impact factor 11.3 citescore Part of a Research Topic The role of immunotherapy in cancer therapy and its challenges - volume II Submission open 36k views 24 articles Editor & Reviewers Edited by S P Susan Prockop Reviewed by K T Kazuki Tanaka M M Mahdi Majidpour Outline Figures and Tables Figure 1 View in article Figure 2 View in article Table 1 Serial laboratory endocrine and myocardial biomarker test results of the patient. View in article Table 2 Serial liver, renal, inflammatory and hematological laboratory parameters of the patient. View in article CASE REPORT article Front. Immunol. , 21 October 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.2003924 Immune checkpoint inhibitor-induced multi-organ immune damage complicated by severe pneumonia: case report T Z Tingrui Zhao 1 † R C Rongzhang Chen 2 † Y M Yuhua Ma 2 G L Gen Li 3 X G Xia Gu 4 Y C Yukai Chen 2 H S He Sun 2 * 1. Department of Clinical Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China 2. Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China 3. Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China 4. Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China See more Article metrics View details Abstract Immune checkpoint inhibitor (ICI) have substantially extended survival in patients with extensive-stage small-cell lung cancer (ES-SCLC), yet they also carry the risk of life-threatening immune-related adverse events (irAEs). Clinical experience in managing multi-organ irAEs (MO-irAEs) complicated by respiratory failure and subsequent severe pneumonia remains exceedingly scarce. Here we report a 71-year-old patient with ES-SCLC (stage IVb, with brain and splenic metastases) who, after four cycles of serplulimab plus chemotherapy, sequentially developed myocarditis, myositis, and hepatic injury. Following premature tapering of glucocorticoid therapy, the patient experienced a recurrence of ICI-related toxicity, manifesting as hypophysitis, primary hypothyroidism, and adrenal insufficiency-alongside respiratory failure-and later acquired multidrug-resistant infection during the treatment course. Through individualized moderate-dose glucocorticoids, comprehensive hormone replacement, and pathogen-directed antimicrobial therapy with eravacycline and ceftazidime-avibactam guided by metagenomic next-generation sequencing (mNGS), the infection was ultimately brought under control and multi-organ dysfunction reversed. This case underscores several key points: (1) serplulimab can precipitate multi-endocrine gland insufficiency, and severe hypothyroidism may be one of the factors contributing to the respiratory failure, mandating a high index of clinical suspicion; (2) glucocorticoid regimens should adhere to adequate initial dosing, sufficient duration, and slow tapering-abrupt discontinuation risks triggering recurrence of ICI-related toxicity; and (3) rapid, precise lower-respiratory-tract pathogen identification coupled with targeted antimicrobial therapy offers particular value in managing severe pneumonia caused by drug-resistant organisms. Introduction Small cell lung cancer (SCLC) accounts for 13–15% of lung cancers and is the most aggressive subtype, with rapid proliferation, strong invasiveness, and early distant spread. At initial diagnosis, 60–70% of patients have extensive-stage disease, and roughly two-thirds have distant metastases; those with brain or liver involvement have a particularly poor prognosis ( 1 ). Although the tumor responds well to first-line chemoradiotherapy, most patients relapse and become resistant within a short time, yielding a 5-year overall survival below 7% ( 2 ). ICI, such as serplulimab, restore T-cell-mediated antitumor immune responses and have become an important treatment modality for ES-SCLC ( 3 , 4 ). With its increasingly widespread clinical use, reports of associated irAEs have also been accumulating. However, ICI can also break immune tolerance while boosting antitumor immunity, resulting in irAEs involving diverse organs such as the skin, gastrointestinal tract, lung, heart, liver, and endocrine glands. When several organ systems are affected at the same time, particularly in the presence of respiratory failure, the overlapping and non-specific clinical features pose major challenges to both diagnosis and management ( 5 ). Here we report a case of successful rescue in a patient who developed MO-irAEs-including myocarditis, myositis, hepatic injury, and multi-endocrine gland damage-after serplulimab treatment, followed by a multidrug-resistant infection, with the aim of providing a reference for the clinical management of similar critical cases. Case presentation The patient was a 71-year-old man weighing 65 kg, with a history of smoking and no history of diabetes, thyroid disease, or autoimmune disease. In August 2024, he presented with cough and dyspnea. Bronchoscopic biopsy pathology confirmed right lung small cell lung cancer, clinical stage IVb (extensive stage), with splenic and brain metastases, and an ECOG performance status score of 1. From September to December 2024, he completed four cycles of chemotherapy combined with immunotherapy at another institution (regimen: etoposide 0.194 g on days 1-3, lobaplatin 40 mg on day 1, and serplulimab 300 mg on day 1, administered every 3 weeks). During treatment, he experienced fatigue, which was not specifically managed. In January 2025, antitumor therapy was suspended due to liver and kidney injury, and the patient was discharged after hepatoprotective treatment. On January 22, the patient was admitted to the VIP ward because of progressive generalized weakness, poor appetite, and fecal and urinary incontinence. Laboratory findings on admission revealed the following: alanine aminotransferase(ALT) 124 IU/L, aspartate aminotransferase(AST) 239.9 IU/L, lactatedehydrogenase(LDH) 667.2 U/L, serum creatinine 115 μmol/L, creatine kinase (CK) 1727 U/L, myoglobin(Mb) 576.8 ng/mL, high-sensitivity cardiac troponin T (hs-TnT) 0.102 ng/mL, creatine kinase-MB(CK-MB) 25.25 ng/mL. Chest CT ( Figure 1A ) demonstrated complete remission (CR) of the lung cancer, along with emphysema, scattered multifocal inflammation in both lungs, and bilateral pleural effusion. He was diagnosed with immune checkpoint inhibitor-related multiorgan injury (myocarditis, myositis, liver injury, kidney injury), graded 3–4 according to Common Terminology Criteria for Adverse Events(CTCAE) criteria, and treated with methylprednisolone 80 mg/d, with gradual tapering. Figure 1 (A) Chest CT on January 22, 2025, one month prior to admission, revealed a complete remission (CR) of the lung cancer. There were emphysemas, scattered inflammatory infiltrations, and bilateral pleural effusion. (B) Chest CT on February 26, 2025, revealed that the cancer remained CR. There was pleural effusion on the right, accompanied by right lower lobe atelectasis and consolidation. (C) Follow-up chest CT on March 18, 2025, showing some absorption of the pulmonary lesions compared with the previous CT, with only a small amount of bilateral pleural effusion remaining. On February 26, 2025, the patient was admitted again because of “worsening generalized fatigue, lethargy, and bilateral lower limb edema”. Physical examination revealed confusion, lethargy, macroglossia with posterior tongue base collapse, hyperpigmented and indurated skin, and pitting edema of both lower extremities. During this hospitalization, he developed respiratory failure (pH 7.27, PaO 2 62.2 mmHg, PaCO 2 86.5 mmHg) and was transferred to the respiratory intensive care unit(RICU). The patient’s family declined endotracheal intubation; consequently, a nasopharyngeal airway was placed, and high-flow nasal oxygen was administered for respiratory support. Admission laboratory results were categorized by organ system as follows: (1) Inflammatory and infectious markers: white blood cell count(WBC) 5.63×10 9 /L, neutrophil percentage(NEUT%) 84.5%, C-reactive protein(CRP) 78.78 mg/L, serum amyloid A(SAA) 145.91 mg/L, procalcitonin(PCT) 0.12 ng/mL, interleukin-6(IL-6) 32.86 pg/mL, CD4 + T-cell count 240 cells/μL, CD8 + T-cell count 107.77 cells/μL, and serum G/GM tests were negative. (2) Cardiac injury markers: CK 438 U/L, hs-TnT 0.29 ng/mL, CK-MB 19.22 ng/mL, Mb 133.6 ng/mL, and BNP 239.4 ng/L. (3) Hepatic, renal, and electrolyte parameters: ALT 50 U/L, AST 49.5 U/L, alkaline phosphatase(ALP) 73.5 U/L, Scr 88.3 μmol/L, serum K + 3.87 mmol/L, serum Na + 124.58 mmol/L. (4) Endocrine hormone panel ( Table 1 , Supplementary Tables S1, S2 ): Table 1 Indicator COR (μg/dL) ACTH (pg/mL) GH (pg/mL) FSH (mIU/mL) PRL (ng/mL) LH (mIU/mL) T (ng/mL) T4 (μg/dL) TSH (μIU/mL) CK (U/L) hs-TnT (ng/mL) CK-MB (ng/mL) Normal range 7-9AM: 4.26-24.85 7-9AM:7.2-63.4 0.03-2.47 1.5-12.4 4.04-15.2 1.7-8.6 1.93-7.4 5.1-14.1 0.27-4.2 50-310 <0.014 <4.87 02/27/25 26.94 5.748 1.27 11.2 1.86 3.36 0.254 <0.42 20.2 192 0.181 7.28 03/05/25 2.956 0.819 12.1 19 1.75 0.598 1 99 98 0.137 3.73 03/11/25 2.086 <1 0.422 11.2 16.3 3.24 0.385 1.4 51.3 40 0.086 1.96 03/27/25 9.485 1.839 0.692 2.32 13.6 <0.3 1.88 6.89 1.1 0.037 0.7 Serial laboratory endocrine and myocardial biomarker test results of the patient. COR, Cortisol; ACTH, Adrenocor ticotropic hormore; GH, Growth Hormone; FSH, Follicle stimulating hormone; PRL, Prolactin; LH, Luteinizing hormone; T, Testosterone; T4, Thyroxine; TSH, Thyrotropin; CK, Creatine Kinase; hs-TnT, High-sensitivity troponin T; CK-MB, Creatine Kinase-MB. Thyroid profile: triiodothyronine (T3) <0.3 ng/mL, thyroxine (T4) <0.42 μg/dL, free triiodothyronine (FT3) <0.39 pg/mL, free thyroxine (FT4) <0.04 ng/dL, thyroid-stimulating hormone (TSH) 20.2 μIU/mL, thyroglobulin (Tg) <0.04 ng/mL, anti-thyroglobulin antibody (TgAb) 31.6 IU/mL, anti-thyroid peroxidase antibody (TPOAb) 239 IU/mL, and thyrotropin receptor-stimulating antibody (TRAb) 4.49 IU/L. Adrenal axis: cortisol 26.94 μg/dL and adrenocorticotropic hormone (ACTH) 5.75 pg/mL. Gonadal and growth hormone axes: growth hormone (GH) 1.27 pg/mL, follicle-stimulating hormone (FSH) 11.2 mIU/mL, prolactin (PRL) 1.86 ng/mL, luteinizing hormone (LH) 3.36 mIU/mL, testosterone 0.25 ng/mL, progesterone 0.28 ng/mL, estradiol 38.9 pg/mL, and insulin-like growth factor-1 (IGF-1) 18.3 ng/mL. (5) Immunological screening: viral hepatitis screening was negative; complement C3 and C4 were within normal limits; antinuclear antibodies were positive at 1:100 and 1:320; ANCA-related antibodies were all negative; autoimmune myositis antibody panel was negative; and immunoglobulin levels were IgG 9.83 g/L, IgM 0.77 g/L, and IgA 1.53 g/L. Electromyography revealed myopathic changes. Abdominal CT showed cirrhotic changes with ascites and diffuse thickening of the colonic wall. Cranial CT demonstrated multiple ischemic and encephalomalacic foci in the bilateral basal ganglia. Chest CT ( Figure 1B ) confirmed CR of the lung cancer, with emphysema, scattered exudative changes in both lungs, right-sided pleural effusion, and right lower lobe atelectasis with consolidation. Echocardiography revealed left atrial enlargement, basal septal hypertrophy, and a small pericardial effusion. Electrocardiography showed sinus rhythm, first-degree atrioventricular block, and widened P waves. Bronchoscopy with bronchoalveolar lavage was performed, and lavage fluid was sent for further analysis. The final diagnoses were immune checkpoint inhibitor-related multi-organ injury (involving myocarditis, myositis, hepatic injury, and renal impairment), clinically suspected hypophysitis, primary thyroiditis, secondary adrenal insufficiency, hypogonadotropic hypogonadism, and type II respiratory failure. After admission, methylprednisolone 40 mg/d was given to control hypophysitis and the systemic immune reaction. Endocrine replacement therapy was initiated simultaneously: for hypothyroidism, levothyroxine sodium was started at 25 μg/d and gradually titrated to 300 μg/d; for hypogonadism, testosterone undecanoate soft capsules were administered as replacement therapy. During the course of the disease, the patient underwent respiratory pathogen testing; bronchoalveolar lavage fluid (BALF) mNGS detected carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP). Based on these results, eravacycline (1 mg/kg q12h ivgtt) and ceftazidime-avibactam (2.5 g q8h ivgtt) was selected for anti-infective therapy. After treatment, the patient’s mental status improved markedly, lethargy and fatigue gradually resolved, endocrine-related hormone levels returned to normal over time, and inflammatory markers and myocardial injury markers declined ( Tables 1 , 2 , Supplementary Tables S1-S4 ). On March 18, repeat chest CT showed gradual resolution of pulmonary exudation and disappearance of pneumothorax ( Figure 1C ). The patient was eventually weaned from noninvasive respiratory support and discharged in stable condition. The complete clinical course is summarized in Figure 2 . Table 2 Indicator ALT (U/L) AST (U/L) LDH (U/L) Scr (μmol/L) K+ (mmol/L) Na+ (mmol/L) WBC (×10 9 /L) NEUT (%) CRP (mg/L) SAA (mg/L) PCT (ng/mL) IL-6 (pg/mL) Normal range <50 17-59 120-246 58-110 3.5-5.1 137-145 3.5-9.5 40-75 0-10 <10 <0.046 0-7 02/26/25 50 49.5 355 88.3 3.87 124.58 5.63 84.5 78.78 145.91 0.116 32.86 03/07/25 43 37 282.7 95.7 4.51 136.95 5.93 78.8 8.61 18.39 0.112 15.61 03/17/25 41 31.1 230.5 78.8 4.4 133.51 4.4 69.7 3.19 <8 0.076 <1.5 03/26/25 38 25 227 89.8 4.21 142.76 7 70.8 80.19 195.75 1.73 63.02 04/02/25 27.9 17.2 211 54.4 4.31 141.25 3.91 69.8 4.44 9.3 0.074 9.88 Serial liver, renal, inflammatory and hematological laboratory parameters of the patient. ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; LDH, Lactate dehydrogenase; Scr, Serum creatinine; K + , potassium; Na + , sodium; WBC, White blood cell count; NEUT%, Neutrophil percentage; CRP, C-reactive protein; SAA, Serum amyloid A; PCT, Procalcitonin; IL-6, Interleukin-6. Figure 2 Management timeline of multi-organ irAEs related to serplulimab combined with MDR infection. Discussion IrAEs can affect multiple systems throughout the body ( 6 ). In cases involving simultaneous involvement of multiple organs, the severe morbidity rate can reach 26%–41%, substantially higher than that observed with single-organ irAEs (3%–20%) ( 7 ). Mortality increases markedly when the heart, skeletal muscle, or endocrine glands are affected ( 8 ). Endocrine glands, with their rich blood supply, are frequent target organs for irAEs ( 9 ). Persistent fatigue is a common early manifestation ( 10 )and is easily confused with tumor progression, potentially leading to missed diagnosis. This case began with fatigue and progressed to a complex clinical course involving simultaneous involvement of the myocardium, skeletal muscle, liver, kidneys, and multiple endocrine axes. The recognition, treatment, and tapering management have several key points. The diagnosis of ICI-related hypophysitis remains clinically elusive. While MRI is the preferred imaging modality, pituitary enlargement is often transient ( 11 , 12 ), with a meta-analysis showing that only 23.7% of affected patients exhibit abnormal enhancement ( 13 ). In our patient, MRI was precluded by a metallic dental prosthesis, necessitating a purely biochemical diagnosis. The diagnosis was supported by synchronous impairment of the adrenal (low ACTH/cortisol), gonadal (low testosterone with inappropriately normal LH/FSH), and growth hormone axes, alongside mild hyperprolactinemia suggestive of stalk compression. Crucially, the pattern of multi-axis involvement and the prior history of ICI exposure effectively ruled out metastatic compression (given the basal ganglia location of metastases) and empty sella syndrome, highlighting that in the absence of MRI, a clinical diagnosis based on two or more endocrine axes involvement is both valid and imperative. However, given this patient’s history of glucocorticoid use, exogenous glucocorticoid-induced adrenal insufficiency cannot be entirely ruled out. In our patient, the combination of elevated TSH, reduced FT4, negative TRAb, and positive TPO-Ab clearly points to primary hypothyroidism rather than central (secondary) hypothyroidism. Most thyroid-related irAEs induced by ICI manifest as overt hypothyroidism, with some patients experiencing a transition from hyperthyroidism to hypothyroidism, which is often permanent. Of note, the patient’s Tg level was extremely low (<0.04 ng/mL), suggesting near-complete destruction of thyroid follicles and an inability to synthesize Tg. This finding provides direct evidence of immune-mediated destructive thyroiditis rather than merely functional hypothyroidism. Following treatment with levothyroxine and methylprednisolone, Tg levels did not recover, further corroborating the sever damage to thyroid follicles. With PD-1 inhibitor monotherapy, the incidence of hypophysitis (approximately 0.4%) is considerably lower than that of primary hypothyroidism (approximately 5%-10%) ( 14 , 15 ). Therefore, the concurrent occurrence of these two conditions is relatively uncommon and likely represents two independent but coexisting immune-related adverse events. One involves T-cell-mediated immune injury to the pituitary gland ( 16 ), resulting in central hypothyroidism; the other involves immune-mediated destructive thyroiditis that directly damages the thyroid gland ( 17 ), leading to primary hypothyroidism. These are not sequential consequences of a single immune mechanism, but rather parallel attacks by the immune system on distinct endocrine organs-the pituitary and the thyroid-following PD-1 pathway inhibition. On admission, ACTH and cortisol were markedly low; however, the 8:00 AM cortisol level on February 27 (26.94 μg/dL, near the upper normal limit) likely reflected residual exogenous glucocorticoids or a falsely low ACTH measurement. Repeat testing confirmed secondary adrenal insufficiency. The presenting hyponatremia (Na + 124.6 mmol/L) with normal potassium (K + 3.9 mmol/L)is consistent with this diagnosis, as the renin-angiotensin-aldosterone axis remains intact in secondary adrenal insufficiency ( 18 ). This case highlights that in elderly lung cancer patients receiving ICI, symptoms such as fatigue, lethargy, and hyponatremia should prompt a comprehensive screen for electrolyte disturbances, cardiac biomarkers, and endocrine dysfunction. In this case, the simultaneous involvement of the ACTH and gonadal axes is consistent with diffuse anterior pituitary insufficiency caused by hypophysitis, with the growth hormone axis also being affected as part of this process. Multiple studies have shown that androgen replacement therapy can improve quality of life, mood, and libido in patients with primary or secondary adrenal insufficiency ( 19 ). In response to the patient’s low testosterone levels, oral testosterone undecanoate was initiated and gradually titrated upward; subsequent follow-up testing confirmed that testosterone levels had returned to normal. Myxedema coma presents with depressed consciousness, hypothermia, and hypoventilation-the latter stemming from central respiratory depression, macroglossia obstruction, and respiratory muscle weakness ( 20 , 21 ). The patient had somnolence, tongue-base collapse, CO 2 reten
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