1. Introduction
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for various hematologic malignancies but is accompanied by substantial infectious and immunologic risks. Post-transplant patients routinely receive broad antimicrobial prophylaxis, including trimethoprim/sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii pneumonia [ 1 ]. However, TMP-SMX is also associated with severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [ 2 , 3 , 4 ]. Pharmacovigilance and epidemiologic data show that TMP-SMX is associated with a disproportionate signal for SJS/TEN compared with several other commonly used antibiotics, as well as that the risk of serious rash is several times higher than for other antimicrobials such as azithromycin or amoxicillin/clavulanate [ 5 , 6 ].
SCARs are life-threatening T-cell-mediated hypersensitivity reactions in which drug antigens are presented by specific human leukocyte antigen (HLA) molecules, leading to the clonal activation of cytotoxic T cells and massive keratinocyte apoptosis [ 2 , 4 , 7 ]. In TEN, CD8 + cytotoxic T cells in lesional skin and blister fluid recognize the culprit drug in an HLA class I restricted manner and induce epidermal necrosis via perforin/granzyme pathways [ 4 , 8 , 9 ].
Clinically, TEN presents with rapidly progressive confluent erythema, blistering, extensive epidermal detachment, and mucosal involvement. It is associated with high acute and long-term morbidity and mortality, particularly in immunocompromised patients such as allo-HSCT recipients [ 2 , 10 , 11 ]. After allo-HSCT, TEN may closely mimic severe acute skin graft-versus-host disease (stage IV), both clinically and histologically, creating a diagnostic dilemma. Careful assessment of drug exposure, organ involvement, and histopathology is essential to distinguish TEN from GVHD and to promptly withdraw the offending agent [ 2 , 11 , 12 ].
The following case describes an allo-HSCT recipient who received TMP-SMX and subsequently developed a rapidly evolving, exfoliative rash. Based on the clinical course, the distribution and severity of skin detachment, mucosal involvement, and the exclusion of alternative etiologies, TMP-SMX-induced TEN was considered the most probable diagnosis. This case highlights the challenges of recognizing TMP-SMX-associated TEN in the post-transplant setting and emphasizes the need for heightened vigilance and early intervention in this high-risk population.
2. Case Presentation
A 64-year-old male with newly diagnosed acute myeloid leukemia (AML) was referred for treatment in June 2024. His medical history was notable for arterial hypertension and dyslipidemia. He had no known drug allergies, no significant family history, and no harmful habits and was not receiving any regular outpatient medications at diagnosis.
Initial laboratory evaluation revealed marked leukocytosis (WBC 215 × 10 9 /L), anemia (hemoglobin 82 g/L), and thrombocytopenia (platelets 22 × 10 9 /L). Bone marrow aspiration demonstrated 86% blasts. Flow cytometry identified a myeloid blast population expressing CD45, cytoplasmic MPO, CD13, CD33, CD34, CD117, and HLA-DR, with an absence of lymphoid markers. Cytogenetic and molecular testing revealed inv(16)(p13;q22) with CBFB–MYH11 fusion, consistent with AML.
Induction chemotherapy with standard “7+3” (cytarabine and anthracycline) was initiated but failed to achieve complete remission, with 15% residual blasts on post-induction marrow assessment. Salvage therapy with venetoclax and azacitidine was started in August 2024. After three cycles, bone marrow examination demonstrated 4% blasts, consistent with morphologic remission.
Given the disease course, the patient proceeded to allo-HSCT. A 10/10 HLA-matched unrelated donor was identified. Reduced intensity conditioning consisted of fludarabine and busulfan, combined with anti-thymocyte globulin (ATG). GVHD prophylaxis included methotrexate and cyclosporine, with a target trough concentration of 200–250 ng/mL. On 26 November 2024, peripheral blood stem cells were infused, delivering 9.2 × 10 6 CD34 + cells/kg. The immediate transplant procedure was uncomplicated.
Platelet engraftment, defined as a platelet count > 20 × 10 9 /L without transfusion support, was achieved on day +21, and neutrophil engraftment (absolute neutrophil count > 0.5 × 10 9 /L) was achieved on day +24. Donor chimerism analysis performed on day +27 demonstrated mixed chimerism, with 63% donor CD34 + cells and 90% donor CD3 + cells. At that time, bone marrow evaluation revealed no detectable genetic abnormalities and cytological examination showed <5% blasts.
The early post-transplant course was marked by mucositis, gastrointestinal symptoms, and febrile neutropenia beginning on day +10. Broad-spectrum antibiotic therapy was initiated; however, blood and site cultures remained negative. Due to persistent fever in the setting of absolute pancytopenia, antimicrobial coverage was progressively escalated to include tigecycline, TMP-SMX, acyclovir, and liposomal amphotericin B, with TMP-SMX initiated on day +18 after allo-HSCT. Following the escalation of antimicrobial therapy, the patient became afebrile and inflammatory markers decreased, with C-reactive protein declining from a peak value of 240 mg/L. A single recurrent febrile episode occurred on day +30, at which time CRP remained low at 8 mg/L. The key clinical events, including TMP-SMX exposure, cutaneous progression, treatment escalation, and recovery, are summarized in Figure 1 .
On day +31 post-transplant, the patient developed a diffuse erythematous maculopapular rash, composed of numerous discrete papules with areas of confluence, predominantly involving the trunk and covering approximately 18% of the body surface area 13 days after TMP-SMX initiation ( Figure 2 ). At that time, the absolute neutrophil count was 3.5 × 10 9 /L and the platelet count was 42 × 10 9 /L. No mucosal involvement was observed. Acute cutaneous graft-versus-host disease was suspected. A punch biopsy of the skin was performed, and topical corticosteroid therapy was initiated. Despite treatment, the rash progressed rapidly in extent, and by day +33 skin, involvement had expanded to approximately 45% of the body surface area, with the rash having spread to the trunk and lower extremities, while dorsal involvement remained unchanged ( Figure 3 ). At this stage, no epidermal detachment or blistering was observed and the clinical presentation was still considered consistent with severe acute cutaneous graft-versus-host disease, prompting the initiation of systemic corticosteroid therapy with intravenous methylprednisolone at a dose of 1 mg/kg/day.
On day +35 post-transplant, the clinical appearance of the skin rash changed markedly, with the development of new tense subepidermal blisters on a diffusely erythematous background, most prominently involving the abdominal skin ( Figure 4 ). This represented a clear morphological progression compared with prior examinations. At this time, the patient reported significant oral mucosal pain, while ocular and genital mucosal involvement was not yet present. The patient remained afebrile; however, inflammatory markers began to rise, with the C-reactive protein level increasing to 35 mg/L.
No gastrointestinal manifestations suggestive of acute GVHD were observed. The patient remained free of diarrhea, nausea, vomiting, and abdominal pain, while bilirubin and liver enzyme levels remained within normal limits throughout the period of cutaneous disease progression.
Given the emergence of blistering lesions and the evolving clinical picture, the differential diagnosis was broadened to include Stevens–Johnson syndrome/toxic epidermal necrolysis in addition to severe acute cutaneous graft-versus-host disease. TMP-SMX was discontinued, and high-dose systemic corticosteroid pulse therapy was initiated.
By day +37 post-transplant, the patient’s condition had progressed to near-total skin involvement, with extensive tense bullae, areas of epidermal detachment, and widespread erosions affecting the trunk and lower extremities ( Figure 5 ). The Nikolsky sign was positive upon examination of the trunk. Mucosal involvement became prominent, with severe oral pain; ocular involvement, characterized by conjunctival hyperemia, conjunctival ulcerations, and bulbar conjunctival erosions; and severe genital pain, with small erosions on the glans penis.
At this time, the patient was subfebrile (maximum temperature 37.7 °C). Laboratory evaluation showed a C-reactive protein level of 31 mg/L, an absolute neutrophil count of 6.4 × 10 9 /L, and a platelet count of 50 × 10 9 /L. Renal function was mildly impaired with a serum creatinine level of 130 µmol/L and a urea level of 14.6 mmol/L.
Following multidisciplinary team evaluation, toxic epidermal necrolysis was favored over acute GVHD with stage 4 skin involvement based on the extent of epidermal detachment, severe multisite mucosal involvement, a positive Nikolsky sign, and clinical evolution. High-dose systemic therapy was initiated, including intravenous immunoglobulin at 0.4 g/kg/day, the escalation of systemic corticosteroids to methylprednisolone at 2 mg/kg/day, and the addition of ruxolitinib at a dose of 10 mg twice daily, as severe acute GVHD could not be completely excluded at that time.
Supportive care was managed jointly by the transplant, dermatology, ophthalmology, urology, and wound-care teams. The patient received intravenous crystalloids with potassium and magnesium replacement guided by daily fluid balance, renal function, and electrolyte monitoring. Blood glucose was monitored regularly and corrected with insulin as needed. Because oral intake was limited by mucosal involvement and overall disease severity, parenteral nutrition was initiated. Analgesia was adjusted according to pain intensity and included paracetamol and morphine. The patient was managed in protective isolation, with surveillance cultures from the skin, oral mucosa, and ocular surface repeated every 48 h. Broad-spectrum antimicrobial therapy was adjusted according to microbiological findings and susceptibility testing, particularly after Pseudomonas aeruginosa was isolated from non-blood sites. Cutaneous care was performed once to twice daily under sterile conditions using gentle irrigation with sterile water, local antiseptic treatment with octenidine when needed, paraffin net dressings with topical silver sulfadiazine, sterile secondary dressings, and external warming measures. Crusted lesions on the face, lips, nose, ears, and eyelids were treated with petrolatum, while loose exfoliated epidermis was gently removed when necessary. Ophthalmological care included eyelid cleansing with normal saline four times daily, artificial tears six times daily, dexamethasone and levofloxacin eye drops four times daily, and tobramycin ointment twice daily. Because of urethral involvement, a Foley catheter was inserted after urologic evaluation.
Based on the extent and severity of cutaneous involvement on day +37, disease severity was assessed using the SCORTEN prognostic score, which was calculated prospectively. The patient had a SCORTEN of 5, indicating a very high predicted mortality risk, with the following criteria present: age > 40 years, underlying malignancy, heart rate > 120 beats per minute, epidermal detachment involving >10% of the body surface area, and hyperglycemia with serum glucose > 250 mg/dL (14 mmol/L).
The histopathological examination of a 5 mm punch biopsy obtained from the back demonstrated extensive epidermal necrosis with numerous necrotic keratinocytes, in some areas involving the full thickness of the epidermis, accompanied by subepidermal blister formation ( Figure 6 ). The dermis showed mild perivascular lymphocytic infiltration with occasional eosinophilic and neutrophilic granulocytes. A mixed leukocytic infiltrate was also present within the epidermis and superficial dermis, predominantly with a perivascular distribution and only limited peri-adnexal involvement. Overall, the histopathological findings were compatible with epidermolytic bullous skin changes characteristic of Stevens–Johnson syndrome/toxic epidermal necrolysis. However, given the post-transplant context, severe acute graft-versus-host disease could not be completely excluded and correlation with the clinical presentation was recommended.
During the period of extensive skin barrier disruption, cultures obtained from the skin, oral cavity, urethra, and ocular surface grew Pseudomonas aeruginosa . Blood cultures remained negative. The isolate was susceptible to meropenem and amikacin, and targeted antimicrobial therapy was administered accordingly, with meropenem continued until day +64 and amikacin until day +65 post-transplant.
The first signs of re-epithelialization were observed between days +50 and +55 post-transplant ( Figure 7 ). Progressive improvement followed, with near-complete re-epithelialization achieved by day +65 ( Figure 8 ). The patient survived the episode of toxic epidermal necrolysis and recovered without permanent cutaneous, ocular, or genital sequelae.
3. Discussion
This case highlights how difficult it can be to distinguish between drug-induced toxic epidermal necrolysis and severe acute graft-versus-host disease in the early post-transplant period, where both can present with very similar features. TEN is a rare, life-threatening severe cutaneous adverse reaction characterized by extensive epidermal necrosis and detachment involving more than 30% of the body surface area [ 13 , 14 ]. It occurs in about 0.4–1.2 cases per million persons per year, but, despite its rarity, mortality remains high, being commonly around 25–35% and even higher in patients with significant comorbidities or immunosuppression [ 14 , 15 , 16 ]. Most cases are drug-induced, typically triggered by medications such as antibiotics, antiepileptics, NSAIDs, and other high-risk drugs, with drugs implicated in roughly 80–90% of SJS/TEN cases [ 17 ].
In the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT), distinguishing TEN from other post-transplant complications is particularly challenging. Transplant recipients are exposed to numerous drugs, including chemotherapy, antimicrobial prophylaxis, and intensive immunosuppression, all of which can trigger severe cutaneous adverse reactions or mimic them [ 18 ]. Profound post-transplant immune dysregulation further complicates the interpretation of new rashes and mucosal disease [ 18 , 19 ]. Crucially, TEN, in this context, may closely resemble severe acute cutaneous graft-versus-host disease, a common and potentially life-threatening complication of allo-HSCT, making accurate clinicopathologic differentiation essential for appropriate management [ 20 , 21 ].
The clinical overlap between TEN and severe acute cutaneous GVHD is substantial, particularly in transplant recipients. Severe forms of acute GVHD can closely mimic TEN [ 20 , 22 ]. Both conditions may begin with diffuse erythematous maculopapular rashes that can rapidly progress to generalized involvement with erythroderma, blistering, and widespread epidermal detachment, often accompanied by mucosal disease and systemic complications [ 20 , 22 , 23 , 24 ]. In transplant patients, these syndromes frequently arise within weeks after transplantation or after changes in immunosuppression, creating major diagnostic uncertainty [ 20 , 24 ]. Key clinical and histopathological features that may help to distinguish severe acute cutaneous GVHD from SJS/TEN in allo-HSCT recipients are summarized in Table 1 . Selected published reports describing TEN after allo-HSCT are summarized in Table 2 . These cases highlight the diagnostic challenges of differentiating TEN from acute GVHD and demonstrate the variable triggers, treatment strategies, and outcomes reported in the literature.
In this case, TMP-SMX was favored as the most likely culprit because the clinical course fit well with drug-induced epidermal necrolysis. The rash appeared 13 days after TMP-SMX was started, progressed while the drug was still being administered, and improved after the withdrawal of the suspected agent together with intensive supportive and immunomodulatory treatment. To make this assessment more objective, we applied the ALDEN algorithm, which is specifically designed for drug causality assessment in SJS/TEN. TMP-SMX received an ALDEN score of 5, corresponding to probable causality. Although severe acute GVHD remained an important competing diagnosis, the rapid progression to extensive epidermal detachment, prominent multisite mucosal involvement, and overall disease evolution were more consistent with TEN.
Acute GVHD remained a serious consideration throughout the early course, particularly because the eruption initially resembled severe cutaneous GVHD. However, the disease pattern became less typical for GVHD as the case evolved. During the period of rapid skin progression, the patient had no diarrhea, nausea, vomiting, abdominal pain, bilirubin elevation, or liver enzyme abnormalities, making gastrointestinal or hepatic GVHD unlikely. Mixed donor chimerism on day +27 (CD34 + 63%, CD3 + 90%) confirmed early post-transplant immune reconstitution but did not provide a specific explanation for the cutaneous syndrome. The timing shortly after engraftment was compatible not only with acute GVHD but also with drug-induced SJS/TEN. Importantly, the eruption progressed despite corticosteroid escalation and evolved into extensive epidermal detachment with prominent oral, ocular, and genital mucosal involvement, a pattern that favored TEN over isolated severe cutaneous GVHD.
Histopathologically, TEN and severe acute cutaneous GVHD share key features, including vacuolar damage of the basal layer, keratinocyte apoptosis, and confluent epidermal necrosis, sometimes with subepidermal blister formation and variable dermal inflammatory infiltrates, limiting the specificity of routine biopsy [ 24 , 25 ]. TEN-like acute GVHD represents the severe end of cutaneous GVHD and may closely resemble drug-induced TEN, both clinically and microscopically [ 20 , 22 , 26 ]. In general, TEN is more often characterized by widespread epidermal necrosis with a relatively sparse inflammatory infiltrate, whereas severe cutaneous GVHD may show more prominent interface dermatitis, satellitosis, adnexal involvement, and lymphocytic infiltration [ 20 , 22 , 25 , 26 ]. Because of this overlap, clinicopathologic correlation remains essential, including timing after transplant, recent drug exposure, gastrointestinal or hepatic GVHD involvement, and detailed histologic assessment. In our case, histology was more consistent with drug-induced epidermal necrolysis but did not definitively exclude severe acute GVHD.
In the present case, several features supported a diagnosis of TEN rather than severe acute cutaneous GVHD. The clinical course was marked by an abrupt transition from a maculopapular rash to widespread blistering and epidermal detachment within a short time frame. The development of tense bullae, a positive Nikolsky sign, and rapid progression to near-total skin involvement are characteristic features of TEN. Additionally, the presence of severe multisite mucosal involvement, including oral, ocular, and genital lesions, strongly favored TEN, as mucosal involvement in GVHD is typically less extensive and evolves differently. The timing and pattern of progression, together with the absence of other organ manifestations typically associated with severe GVHD, further supported this interpretation.
Exposure to TMP-SMX represented a key etiologic factor in this case. TMP-SMX is one of the most commonly implicated drugs in TEN and is widely used for Pneumocystis jirovecii pneumonia prophylaxis in transplant recipients [ 5 , 6 ]. The time between TMP-SMX administration and the onset of symptoms in our patient is consistent with the known latency period of drug-induced TEN, which typically ranges from 1 to 3 weeks after exposure [ 5 , 11 ]. In addition, immunocompromised patients may have an increased susceptibility to severe drug reactions, further supporting the role of TMP-SMX as the likely trigger in this case.
The management of TEN in the post-transplant setting remains complex and is not standardized. In this case, treatment included high-dose systemic corticosteroids, intravenous immunoglobulin (IVIG) and ruxolitinib, along with intensive supportive care. While the use of systemic corticosteroids and IVIG in TEN remains controversial, these therapies are commonly employed in severe cases, particularly when differentiation from GVHD is uncertain [ 27 , 28 , 29 ]. Ruxolitinib, a JAK 1/2 inhibitor, was introduced because severe acute GVHD could not be completely excluded at the time of clinical deterioration and because of its established role in steroid-refractory GVHD. Although its immunomodulatory effects, mediated through the inhibition of JAK-STAT-dependent cytokine signaling, may theoretically have contributed to controlling the severe inflammatory response, its specific role in TEN remains uncertain [ 30 , 31 ]. Given the concurrent withdrawal of TMP-SMX, escalation of corticosteroids, administration of IVIG, and intensive supportive care, the individual contribution of ruxolitinib to clinical recovery cannot be determined. Supportive care, including meticulous wound management, infection control, fluid and electrolyte balance, and multidisciplinary involvement, remains the cornerstone of TEN management and is critical for patient survival.
The severity of disease was reflected by a SCORTEN of 5. In the original SCORTEN validation study, a score of ≥5 was associated with a predicted mortality of >90% (95% confidence interval, 55.5–99.8%) [ 32 ]. However, SCORTEN has not been specifically validated in allo-HSCT recipients and should therefore be interpreted here as a marker of severe disease rather than a precise individualized mortality estimate. Despite this, the patient achieved complete recovery without long-term sequelae. This favorable outcome likely reflects early recognition of the evolving clinical picture, prompt discontinuation of the suspected offending agent, and initiation of aggressive systemic and supportive therapy. The absence of bloodstream infection, despite documented colonization with Pseudomonas aeruginosa and the implementation of appropriate targeted antimicrobial therapy, may also have contributed to the positive outcome.
This case highlights the significant diagnostic challenges associated with severe cutaneous reactions in the early post-transplant period. Distinguishing between TEN and severe acute cutaneous GVHD is critical, as the underlying pathophysiology, management strategies, and prognostic implications differ substantially. Clinicians should maintain a high index of suspicion for drug-induced TEN in patients receiving high-risk medications such as TMP-SMX, particularly when rapid clinical deterioration, blister formation, and extensive mucosal involvement are observed. Early multidisciplinary evaluation, including dermatologic and histopathologic assessment, is essential to guide appropriate management.
Table 1
The clinical and histopathological features useful in distinguishing severe acute cutaneous GVHD from SJS/TEN in allo-HSCT recipients [ 2 , 4 , 18 , 26 , 33 ].
| Feature | Severe Acute Cutaneous GVHD | SJS/TEN |
| Mechanism | Donor T-cell activation against the recipient cells | Hypersensitivity reaction with cytotoxic T lymphocytes and natural killer cell activation |
| Typical trigger | Allo-HSCT with donor alloreactivity | Medications most common, infections less common |
| Timing | Usually within first 100 days after allo-HSCT | Usually 1–3 weeks after culprit drug exposure |
| Initial rash | Maculopapular eruption, often involving the face, palms, and soles | Painful erythematous or dusky lesions that may rapidly become confluent |
| Mucosal involvement | In TEN-like acute GVHD, bullae, epidermal detachment, and mucosal involvement may closely mimic SJS/TEN | Common and often prominent: oral, ocular, and genital |
| Nikolsky sign | May be present in severe cases | Often positive |
| Systemic manifestations | May be accompanied by gastrointestinal or hepatic GVHD, including diarrhea, abdominal pain, cholestasis, or bilirubin elevation | Fever, malaise, pain, mucosal involvement, fluid loss, infection risk, and multiorgan complications in severe cases |
| Laboratory findings | No specific diagnostic laboratory marker. Bilirubin or liver enzyme abnormalities may support hepatic GVHD when present | No specific diagnostic laboratory marker; SCORTEN variables may reflect severity, including renal dysfunction, hyperglycemia, bicarbonate decrease, and tachycardia |
| Histology | Interface dermatitis with basal vacuolization, apoptotic keratinocytes, satellitosis, and more prominent lymphocytic/interface inflammation | Full-thickness epidermal necrosis with subepidermal blistering and usually sparse dermal inflammatory infiltrate |
| Expected therapeutic response | Usually managed by the escalation of immunosuppression. Response to steroids or GVHD-directed therapy supports GVHD | Requires the withdrawal of the suspected culprit drug. Improvement after drug withdrawal supports SJS/TEN |
| Key diagnostic clue | Concurrent gastrointestinal or hepatic GVHD may support diagnosis | Recent high-risk drug exposure, rapid detachment, and prominent mucosal involvement |
Table 2
Selected published reports of TEN after allo-HSCT [ 12 , 20 , 22 , 34 , 35 , 36 , 37 ].
| Study | Age/Sex | Underlying Malignancy | Transplant Type (Donor/HLA Match) | Concurrent GVHD | Suspected Trigger | Treatment | Outcome |
| Hilgendorf et al., 2007 [ 12 ] | - | Multiple myeloma | MUD (HLA-matched) | No active GVHD reported | TMP-SMX, levofloxacin, amoxicillin/clavulanate | Steroids, IVIG, supportive care | Recovered |
| Macedo et al., 2014 [ 20 ] | 23/F | T-cell lymphoma | Mismatched unrelated donor | Grade IV GI GVHD | Cefepime | Steroids, IVIG, supportive care | Died |
| Gomulka et al., 2014 [ 34 ] | 67/F | CLL | Allo-HSCT | Grade IV intestinal GVHD | Voriconazole | IVIG, supportive care | Recovered |
| Chen et al., 2018 [ 35 ] | 67/M | AML | Allo-HSCT | Uncertain | TMP-SMX, NSAIDs | Etanercept, supportive care | Recovered |
| Morishige et al., 2019 [ 36 ] | 73/M | ATLL | Haploidentical HSCT | GVHD/TEN overlap | Mogamulizumab, Lenalidomide | Steroids, IVIG, supportive care | Recovered |
| Vera et al., 2022 [ 22 ] (Case 1) | 58/M | AML | Allo-HSCT | Acute GVHD present | TMP-SMX ± voriconazole | IVIG, etanercept, supportive care | Died |
| Vera et al., 2022 [ 22 ] (Case 2) | 67/F | MDS | MUD HSCT | Acute GVHD present | TMP-SMX | Infliximab, Cyclophosphamide, supportive care | Died |
| Chromik et al., 2024 [ 37 ] | 24/M | Refractory Hodgkin lymphoma | MUD 10/10 | Initially diagnosed as grade I aGVHD | Prior nivolumab exposure | Burn center care, amniotic membranes | Recovered |
| Present case | 64/M | AML | MUD 10/10 | Acute GVHD considered but not confirmed | TMP-SMX | Steroids, IVIG, supportive care, ruxolitinib | Recovered |
4. Conclusions
Toxic epidermal necrolysis should be considered in allo-HSCT recipients presenting with rapidly progressive cutaneous rashes, particularly in the context of high-risk drug exposure such as TMP-SMX. Differentiating TEN from severe acute cutaneous GVHD remains challenging due to significant clinical and histopathological overlap, but features such as abrupt blistering, extensive mucosal involvement, and disease evolution may aid distinction. Early recognition and prompt withdrawal of the offending agent, together with aggressive supportive and immunomodulatory therapy, are critical for improving outcomes. This case underscores the importance of maintaining diagnostic vigilance in the post-transplant setting, where timely decisions can be lifesaving.
Acknowledgments
Generative AI was not used for text, study design, data collection, data analysis, interpretation of results, clinical decision-making, or figure generation.
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Author Contributions
Conceptualization, T.T., I.G., D.V. and R.G.; investigation, T.T. and R.J.G.; writing—original draft preparation, T.T., I.G., M.K. and M.B.; writing—review and editing, T.T., E.K., R.D., M.R., R.J.G., A.V., R.G. and D.V.; visualization, T.T. and E.K.; supervision, T.T., R.G. and D.V.; project administration, T.T. and A.V. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
Committee approval was not required for this retrospective single-patient case report under Lithuanian national legislation. According to the Law on Ethics of Biomedical Research of the Republic of Lithuania, No. VIII-1679, Article 2, Paragraph 7, biomedical research is defined as the verification of biomedical science hypotheses by scientific research methods, aimed at developing scientific knowledge about human health, diseases, diagnosis, treatment or prevention. This manuscript is a retrospective descriptive case report based on anonymized routine clinical data and did not involve a research intervention, prospective recruitment or hypothesis-testing research procedures. Written informed consent for publication was obtained from the patient. Link to the Law on Ethics and Biomedical Research: https://www.e-tar.lt/portal/en/legalAct/TAR.234B15954C2F/WYYgOFBIYQ (accessed on 14 May 2026).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.
Conflicts of Interest
The authors declare no conflicts of interest.
Abbreviations
The following abbreviations are used in this manuscript: TEN Toxic epidermal necrolysis SJS Stevens–Johnson syndrome Allo-HSCT Allogeneic hematopoietic stem cell transplantation GVHD Graft-versus-host disease TMP-SMX Trimethoprim/sulfamethoxazole SCAR Severe cutaneous adverse reaction HLA Human leukocyte antigen AML Acute myeloid leukemia MDS Myelodysplastic syndrome CLL Chronic lymphocytic leukemia ATLL Adult T-cell leukemia/lymphoma MUD Matched unrelated donor ATG Anti-thymocyte globulin CRP C-reactive protein BSA Body surface area NSAID Nonsteroidal anti-inflammatory drug IVIG Intravenous immunoglobulin JAK Janus kinase JAK-STAT Janus kinase–signal transducer and activator of transcription pathway
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