Stevens‑Johnson syndrome induced by fluoroquinolones in a patient with colon cancer: A case report and literature review

Introduction

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, life-threatening cutaneous adverse reactions, characterized by widespread mucocutaneous necrosis and epidermal detachment. In the most severe cases, these conditions can have mortality rates approaching 50%, which necessitates rapid diagnosis and timely intervention to improve clinical outcomes. Although sulfonamides and β-lactam antibiotics remain the most frequently implicated agents in antibiotic-induced SJS/TEN, emerging evidence indicates that fluoroquinolones account for ~4% of cases, emphasizing the need for clinical vigilance (1-3).

The pathophysiological mechanisms of fluoroquinolone-induced SJS/TEN involve intricate T cell-mediated immune responses (4,5). Clinical manifestations typically evolve from an initial erythematous rash to extensive blistering and epidermal detachment, usually accompanied by severe mucosal involvement. Previous reports have documented six cases of fluoroquinolone-induced SJS/TEN, including four cases using ocular formulations and two using oral formulations. From these, five patients successfully recovered following the administration of supportive care, while the treatment and outcome of one patient were not mentioned. However, the clinical course and outcomes in oncological patients, particularly those with abdominal malignancies, remain inadequately characterized (Table I) (6-11).

Table I Case reports of fluoroquinolone-induced SJS/TEN.

Table I

Case reports of fluoroquinolone-induced SJS/TEN.

Present situation	Dosage of fluoroquinolones	Clinical manifestations	ADR type	Treatments	Prognosis	(Refs.)
Ocular inflammation	Ciprofloxacin p.o/moxifloxacin gtto.	Fever, erythematous rashes over face and upper limbs, dyspnea	SJS	Corticosteroids, antibiotics	Recovered after 10 days	(6)
Vasectomy	Ciprofloxacin p.o. 500 mg qd	Pruritic, blistering rash	SJS	-	-	(7)
Ocular inflammation	Moxifloxacin gtto.	Rashes over trunk	SJS	Supportive care	Recovered within 8 days	(8)
Bacterial conjunctivitis	Moxifloxacin gtto. bid	Fever, rashes over entire body	SJS/TEN	Supportive care	Recovered	(9)
Urinary tract infection	Ciprofloxacin p.o. 500 mg qd	Pain, epidermal detachment and oral mucosal ulcerations	SJS/TEN	Supportive care, corticosteroids, antibiotics	Recovery over 4 weeks	(10)
Allergic diseases	Ofloxacin gtto.	Fever, rashes over the palms, oral mucositis	SJS	Supportive care, corticosteroids, antibiotics	Recovery in 30 days	(11)

[i] SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis; ADR, adverse drug reaction; p.o., oral administration; gtto., for ocular use; qd, once daily; bid, twice daily.

Recent advances in diagnostic technologies have substantially improved the capability to detect SJS/TEN in the early stages. Granulysin, a cytotoxic protein that is markedly elevated in blister fluid and serum during the acute phase, has been a promising biomarker for an early diagnosis (12). While the SCORTEN scoring system remains the most widely adopted tool for mortality risk stratification (13), its predictive accuracy in the context of increasingly comprehensive intensive care and biological therapies requires further evaluation (14). The SCORTEN system incorporates seven independent clinical variables, including age ≥40 years, presence of cancer, >10% epidermal detachment, heart rate ≥120 bpm, blood urea nitrogen >10 mmol/l, serum glucose >14 mmol/l and serum bicarbonate <20 mmol/l. Each criterion scores one point, with the total score ranging from 0 to 7(13).

The present study reports a rare case of levofloxacin-induced SJS/TEN in a patient with colon cancer. This study aims to clarify the importance of an early diagnosis for SJS/TEN and identify the factors influencing prognosis, which may help inform therapeutic strategies in similar cases.

Case report

A 55-year-old male patient was admitted to Hubei Cancer Hospital (Wuhan, China) in June 2024, presenting with a 1-month history of abdominal distension. Colonoscopy revealed a neoplasm occupying three-quarters of the lumen in the ascending colon near the hepatic flexure, covered with feces and opaque liquid. Biopsy confirmed adenocarcinoma. Subsequent positron emission tomography-computed tomography examination demonstrated a malignant tumor of the ascending colon, with retroperitoneal and mesenteric lymph node metastases, as well as the presence of ascites (data not shown). During the initial hospitalization for the management of intestinal obstruction, the patient underwent an urgent double-lumen ileostomy. Considering the patient's documented hypersensitivity to cefmetazole, antimicrobial therapy was initiated with intravenous levofloxacin at a dose of 0.5 g once daily. Postoperatively, the patient experienced intermittent febrile episodes, with peak temperatures reaching 38.5˚C. Lysine aspirin (1.8 g once daily for 3 days) was administered as an antipyretic.

On the third postoperative day, both abdominal drainage fluid and sputum samples were collected and subjected to microbiological examination. At 5 days after submission, the microbiological analysis revealed a negative result for the sputum culture, whereas Enterococcus faecalis was identified in the drainage fluid, exhibiting resistance to levofloxacin. At the same time, the patient developed a widespread erythematous rash affecting the face, neck and upper trunk, along with generalized weakness, oral mucosal ulceration and mild conjunctival hemorrhage. Laboratory findings at this time included marked hypoalbuminemia (serum albumin, 26.2 g/l; reference range, 40-55 g/l), elevated blood urea nitrogen (9.8 mmol/l; reference range, 1.7-8.3 mmol/l) and increased procalcitonin levels (1.252 ng/ml; reference range, <0.05 ng/ml) (Fig. 1). The patient declined a skin biopsy. Considering drug allergic reactions and findings from microbiological testing, the clinical team promptly discontinued levofloxacin and initiated a treatment of dexamethasone (10 mg once daily for 6 days) and promethazine (25 mg once daily for 6 days) to manage the hypersensitivity reaction. At this stage, the SCORTEN score was 2, determined according to the patient's age (>40 years) and the presence of cancer (Table II).

Figure 1 Serum levels of (A) albumin (reference range, 40-55 g/l), (B) urea nitrogen (reference range, 1.7-8.3 mmol/l) and (C) procalcitonin (reference range, <0.05 ng/ml) in the patient with colon cancer. Blood samples were collected preoperatively and on different days following levofloxacin treatment.

Table II SCORTEN score and ABCD-10 score of the present case.

Table II

SCORTEN score and ABCD-10 score of the present case.

	8 Days after levofloxacin		14 Days after levofloxacin
Criterion	SCORTEN score	ABCD-10 score	SCORTEN score	ABCD-10 score
Age, years
≥40	1	-	1	-
≥50	-	1	-	1
Presence of cancer	1	2	1	2
>10% TBSA involved	0	0	1	1
Tachycardia ≥120 bmp	0	-	0	-
Urea nitrogen >10 mmol/l	0	-	1	-
Glycemia >14 mmol/l	0	-	0	-
Serum bicarbonate <20 mmol/l	0	0	0	0
Dialysis before presentation	-	0	-	0
Total score	2	3	4	4

[i] TBSA, total body surface area.

Following an additional 6-day period, the patient's skin condition not only failed to improve but also deteriorated notably, as evidenced by the development of central blisters within erythematous rashes and the presence of Nikolsky's sign (Fig. 2A). As the clinical course progressed, and possibly due to insufficient early corticosteroid therapy before the diagnosis of Stevens-Johnson syndrome (SJS), new erosive lesions appeared around the perianal and scrotal regions (Fig. 2B), while conjunctival hyperemia progressively worsened (Fig. 2C). Serial laboratory testing revealed persistent hypoalbuminemia (26.4 g/l), worsening azotemia (urea nitrogen, 13.94 mmol/l) and a sustained elevation of procalcitonin (1.004 ng/ml) (Fig. 1). Due to the increased blood urea nitrogen and the expansion of the total body surface area, the SCORTEN score increased to 4 (Table II). Based on ALDEN scoring (15) (levofloxacin: 6, ‘very likely’; lysine aspirin: 0, ‘unlikely’), a dermatological consultation confirmed that levofloxacin was the culprit drug for the diagnosis of SJS.

Figure 2 (A) Blisters emerging at the center of the rash. (B) Erosions in the perianal region. (C) Notably worsening conjunctival hyperemia. (D) Slight improvement of the conjunctival hyperemia. (E) Extensive epidermal detachment.

In view of the progressive deterioration of skin symptoms and the presence of purulent secretions, along with the prior antibiotic test results, the patient was administered methylprednisolone (1.5 mg/kg/day), vancomycin (0.5 g every 12 h) and intravenous immunoglobulin (5 g/day). This treatment regimen resulted in a slight improvement in the conjunctival hyperemia (Fig. 2D). However, 4 days later, the syndrome recurred, accompanied by progressive worsening of the epidermal detachment (Fig. 2E). Follow-up laboratory tests showed a substantial increase in serum urea nitrogen levels to 39.77 mmol/l (reference range, 1.7-8.3 mmol/l) (Fig. 1), which is a critical prognostic factor associated with disease severity and clinical outcomes.

The patient's clinical course was complicated by the onset of melena, prompting an urgent transfer from the specialized cancer hospital to Hubei General Hospital (Wuhan, China) for multidisciplinary management. Despite aggressive intensive care and interventions, the patient developed septic shock and subsequently progressed to multiple organ dysfunction syndrome, resulting in death within 1 week.

Discussion

SJS/TEN frequently presents with non-specific symptoms, including fever, ocular irritation, flu-like symptoms and cutaneous discomfort (16). Acute episodes of SJS/TEN are characterized by irregularly shaped, painful erythematous lesions with central blisters, indistinct borders and rapid coalescence. This progression typically results in extensive epidermal detachment and a positive Nikolsky sign (17,18). Mucosal involvement is a defining feature, commonly affecting the eyes, oral cavity, nasal passages and genital regions. Gastrointestinal mucosal injury, including ulceration, erosion and congestion, may also occur, occasionally presenting as symptoms such as hematochezia or diarrhea (19).

SJS/TEN is classified as type IVc hypersensitivity. Histologically, it is distinguished by keratinocyte apoptosis or necrosis (20). This reaction occurs when T cell receptors recognize drug antigens or metabolites presented via human leukocyte antigen (HLA). Type IVc hypersensitivity mainly induces target cell death by cytotoxic T cells (CTL), releasing cytokines such as granulysin, granzyme B and perforin, or through direct interaction of Fas/FasL. This cascade induces keratinocyte apoptosis and varying degrees of epidermal necrosis, which are hallmarks of SJS/TEN (5,20,21).

The progression of symptoms in the present patient, characterized by initial non-specific manifestations that gradually evolved into extensive epidermal detachment (affecting 16% of the total body surface area), highlights the diagnostic challenges associated with SJS/TEN. According to the ALDEN scoring system (15), the optimal interval between initial drug exposure and the onset of reaction ranges from 5 to 28 days. In the present case, the patient developed skin eruptions on the eighth day after starting levofloxacin, which falls with this high-risk timeframe. Moreover, granulysin has been recognized as a critical mediator of keratinocyte apoptosis in SJS/TEN, with serum levels reportedly rising 2 to 4 days prior to the appearance of clinical symptoms (22). The early detection of serum granulysin, particularly at the onset of non-specific fever or flu-like prodromal symptoms, may facilitate a timely diagnosis and intervention. The development of rapid immunochromatographic assays for granulysin represents an important advancement, offering the potential for preventive measures before extensive epidermal detachment occurs (23). Nevertheless, routine clinical application of granulysin detection in CTL-induced severe disorders has yet to gain widespread adoption (24). In the present case, granulysin was not measured, mainly since the patient displayed rapid clinical progression; by the time SJS/TEN was diagnosed, the disease had already advanced, limiting the diagnostic value of granulysin testing at that stage.

The primary treatment for SJS/TEN centers on comprehensive supportive care, which includes wound management, nutritional support, and systemic therapies such as high-dose corticosteroids, intravenous immunoglobulins, cyclosporine and TNF-α inhibitors (20). However, managing SJS/TEN in patients with cancer presents unique challenges, particularly concerning the use of high-dose corticosteroids. Although these agents remain a cornerstone of treatment, their immunosuppressive effects must be carefully balanced against the risk of secondary infections in immunocompromised patients. A prospective study involving 64 patients with SJS/TEN demonstrated that serum granulysin levels increase during the early and acute phases of skin toxicity and decrease during recovery (12). This suggests that granulysin can serve as an ideal biomarker for guiding the tapering or discontinuation of immunosuppressive therapy, potentially reducing complications such as infections and disseminated intravascular coagulation.

While the SCORTEN score is still widely used as a prognostic tool for SJS/TEN, its predictive accuracy may be compromised by advancements in supportive care. The recently proposed ABCD-10 score (25), which incorporates renal dysfunction parameters, was developed to enhance prognostic accuracy in SJS/TEN. Nevertheless, its superiority over the established SCORTEN system remains controversial (26). According to previous studies, the SCORTEN system has demonstrated better performance than the ABCD-10 system in predicting mortality among patients with epidermal necrolysis, although there is evidence of time-associated deterioration in the calibration, leading to an overestimation of mortality risk (26,27). Specifically, in the present study, the SCORTEN score was calculated at the onset of skin lesions (score=2) and after disease progression (score=4). The corresponding predicted mortality risks were 12.1 and 58.3%, respectively, according to the original SCORTEN publication (13). In this case, given that renal dialysis was not performed, the primary distinction between the SCORTEN and ABCD-10 scoring systems was the allocation of points for malignancy: SCORTEN assigns 1 point for the presence of cancer, whereas ABCD-10 assigns 2 points (Table II). Some studies suggest that malignant tumors and certain autoimmune skin diseases may contribute to the development of secondary capillary leak syndrome (28-30). In patients with SJS/TEN, the skin and mucosal surfaces act as open wounds, leading to substantial fluid loss, protein depletion and edema (31). Consequently, malignant ascites and hypoalbuminemia may serve as potential prognostic indicators, underscoring the critical need for malignancy-specific risk stratification tools.

The present study has several limitations that warrant careful consideration. Firstly, the single-case design restricts the generalizability of the findings, although the detailed documentation of clinical progression provides valuable insights. Secondly, the level of granulysin was not measured in this case, and further exploration of its potential role in guiding treatment decisions is warranted. Lastly, the complicated relationship between malignancy-associated immune dysregulation and adverse drug reactions necessitates more comprehensive research.

In addition to antibiotics, antiepileptics, allopurinol and antiviral agents have also been associated with severe cutaneous adverse reactions (SCARs). Accumulating evidence suggests that these adverse reactions are closely linked to pharmacogenomics (32). For example, Chung et al (33) first reported in 2004 that HLA-B*15:02 may serve as a genetic marker for carbamazepine-induced SJS/TEN. Building on this finding, it was further identified that HLA-B*58:01 is associated with allopurinol-induced SCARs in various Asian populations (5,34). Lonjou et al (35) demonstrated that HLA-B*38 is linked to sulfamethoxazole-induced SJS/TEN in European individuals, while HLA-B*35:05 and HLA-Cw*04:01 were found to be associated with nevirapine-induced SJS/TEN in Thai and African individuals, respectively (36,37).

Therefore, future research should focus on developing malignancy-specific risk prediction models that incorporate biomarkers such as granulysin. Additionally, integrating pharmacogenomic testing into routine clinical practice may enhance the ability to prevent severe cutaneous adverse reactions in susceptible individuals.

In conclusion, early and accurate diagnosis is essential for optimizing therapeutic outcomes in SJS/TEN. The results indicate that malignant ascites and hypoalbuminemia may serve as prognostic indicators in patients with SJS/TEN and abdominal malignancies. These findings warrant validation in future large-scale, multicenter studies.

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

Authors' contributions

YZ conceived the study, collected, analyzed and interpreted the data, and drafted the manuscript. GH analyzed the data, produced the graphs and revised the manuscript. HL designed and supervised the study and reviewed the manuscript. YZ and HL confirm the authenticity of all the raw data. All authors have read and approved the final version of the manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Written informed consent was obtained from the patient before death for the publication of the study and any potentially identifiable images or data, specifically including images showing the face.

Competing interests

The authors declare that they have no competing interests.

References