A Rare Multisystem Presentation of Fixed Drug Eruption Due To Aceclofenac in A Patient with Bilateral Renal Calculi and Stasis Eczema – A Case Study

(A)Clearly visible tense bulla with hyperpigmentation around the bulla on the palm side of the hand. (B) Residual hyperpigmentation with central bullous changes seen on the palm, typical of the fixed drug eruption.

Table 1: Summary of Laboratory Investigations

Above normal range. HPF = High Power Field. (Sree Abirami Hospital Laboratory Report, 29/05/2026)

2.4 Imaging: USG Abdomen (Abirami Ultra Sonography Centre, 29/05/2026)

Table 2: USG Abdomen Findings — Mr. Manikandan Rao (Age 48/Male, Date: 29/05/2026)

▲ Abnormal findings. CT KUB is recommended for further evaluation of calculi.

3. Diagnosis

3.1 Primary Diagnosis

Fixed Drug Eruption (FDE) - Aceclofenac-Induced / Stasis eczema

3.2 Differential Diagnosis

• Stasis Eczema (if bilateral lower limb involvement, alcoholism and venous insufficiency are given, then it is considered as Stasis Eczema).
• Diagnosis of pemphigus vulgaris requires an evaluation of the Nikolsky sign.Pemphigus vulgaris, oral erosion, requires evaluation of the Nikolsky sign.
• Bullous lesions + mucous membrane involvement (excluding by localization, duration, pattern): Stevens-Johnson Syndrome / TEN.
• Erythema multiforme (no target lesions found)
• Bullous pemphigoid (age group, bilateral palmar distribution; IgG anti-BP180 not tested).

Table 3: Diagnostic Criteria for FDE - Applied to This Case (Based on Mahboob & Haroon, 1998; Lee et al., 2017)

4. Management

4.1 Dermatology Treatment (Govt. Medical College Hospital, The Nilgiris)

Table 4: Prescribed Treatment Protocol

Note: Aceclofenac was found to be the cause and was promptly withdrawn. Orders placed: Investigations: USG abdomen + pelvis, Arterial Doppler B/L legs (DVL, 5/6/26).

4.2 Urological Follow-Up

Given the USG findings (small left renal stones, cortical cyst, fatty liver Grade I), a CT KUB was recommended to further characterise the stones. Uroprotective agents were continued on. Urine culture was recommended as active UTI was ruled out due to mildly elevated pus cells. Counselling of dietary modification (low oxalate, increased fluid) was provided.

5. Discussion

5.1 Epidemiology and Pathophysiology of Aceclofenac-Induced FDE

NSAIDs are one of the major groups of drugs responsible for FDE, which make up about 6–16% of all reported cutaneous adverse drug reactions in India⁶ along with antimicrobials and anticonvulsants. Aceclofenac is a phenylacetic acid derivative with preferential COX-2 inhibition which is one of the most widely used NSAIDs in the Indian subcontinent especially post orthopaedic and urological surgery⁷.

Immunopathogenesis of FDE involves activation of CD8+ T-lymphocytes at the site of the lesion, which on subsequent re-exposure release mediators of cell-mediated immunity such as perforin and granzyme B, which are responsible for the apoptosis of keratinocytes and the subsequent separation of the epidermis and dermis to form bullae^8,9. FDE differs from other drug reactions by the recurrence of the reaction at the same site resulting in “memory T cells” in the dermis and in the epidermis. Studies in recent years have suggested that drug specific MHC-I restricted immune activation and memory intraepidermal effector T cells (CD69+CD103+) are the mechanism¹⁰.

FDE has a well-established predilection for involvement of acral sites (palms, soles) for mucosal surfaces. Palmar involvement as in this case can be confusing or difficult to diagnose because of the similar appearance with eczema of palms and soles, pompholyx, and contact dermatitis¹¹.

5.2 Chronological Timeline and Drug Causality Assessment

Table 5: Clinical and Treatment Timeline

Causality assessment was done by using the Naranjo Adverse Drug Reaction Probability Scale. The patient's score was +6 due to the following reasons: prior literature regarding aceclofenac-FDE (+1); improvement upon rechallenge (+1); recurrence on continued use (+2); the presence of alternative explanations that were not related to his current disease (+1); objective documentation of drug reaction (+1)¹².

5.3 The Significance of Co-existing Urological Disease

Physiologic nephrolithiasis is associated with renal cortical cyst, which adds to the clinically relevant pharmacokinetic consideration. NSAIDs such as aceclofenac are excreted to a large extent by the kidney. Drug hypersensitivity reactions may occur at lower threshold levels due to prolonged plasma levels which can result from impaired renal clearance (due to obstructive uropathy, e.g., from previous DJ stenting or remaining calculi) [13]. The USG shows the fatty liver as Grade I, which further indicates reduced hepatic Phase I metabolism of aceclofenac (CYP2C9) that may lead to increased formation of the reaction metabolites involved in the pathogenesis of FDE¹⁴.

Another metabolic risk factor of chronic alcoholism (defined here as 15 years' duration) is CYP2E1 induction and CYP2C9 activity suppression, drug protein binding (decreased albumin), impaired immune regulation, and hepatic steatosis. The “perfect storm” for drug hypersensitivity is the combination of alcohol-related hepatic changes, renal insufficiency, and chronic NSAID use¹⁵.

Also worth noting is that stasis eczema features as a differential diagnosis and may also be a co-morbidity. Chronic venous insufficiency (suggested by the DVL team and requires arterial Doppler B/L legs) can result in palmar/plantar eczematous changes, hyperpigmentation, which can mimic or mask FDE. Arterial Doppler was ordered to rule out peripheral arterial disease which may be affecting skin changes on lower extremities¹⁶.

5.4 Novelty and Contribution to Literature

Table 6: Comparison with Published Cases of NSAID-Induced FDE

The features of this case which make it different from previous reports are: (1) The temporality with DJ stenting and RIRS procedures where aceclofenac was the main post-operative analgesic, (2) Trifocal FDE (bilateral palms, lower limb, and oral mucosa), which is a rare distribution pattern, (3) Complex pharmacokinetic milieu with the presence of renal calculi, cortical cyst, and Grade I fatty liver, (4) Alcohol use as a modifying factor for drug metabolism and immune response, and (5) The co-existence of features that suggest stasis eczema as an overlapping dermatological condition, which adds to the diagnostic complexity.

6. Patient Perspective

The bilateral bullae caused the patient a great deal of distress and did not allow him to perform his daily routines and work. He did not know that it was the pain medications causing his skin rash as he had thought that the rash was due to an infection or an allergic reaction to some unknown environmental triggers. He explained that the reason for the appearance of the drug, and questioned him about what he would do if he had pain in the future in connection with the condition of his kidneys. Advised about alternative analgesics (paracetamol, tramadol and selective COX-2 inhibitors with caution) and provided with a Medic Alert Card to avoid using Aceclofenac.

7. Conclusions

A rare and clinically complex case of aceclofenac induced bullous fixed drug eruption in a patient with multifaceted urological history, chronic alcoholism and fatty liver Grade 1. The case highlights the following key points in the clinical management of paediatric patients:

• The use of aceclofenac, a commonly used drug for post-urological surgery in India, should be taken as an important cause of FDE, especially in patients with impaired renal or hepatic clearance.
• A more severe form is called Trifocal FDE (bilateral palms, leg and oral mucosa) which requires prompt recognition and differentiation from SJS/TEN and the autoimmune bullous diseases.
• In patients with overlapping disease systems, a multidisciplinary approach is mandatory that integrates dermatology and urology.
• Drug hypersensitivity reactions could be exacerbated by the chronic alcoholism or hepatic steatosis, which may affect the metabolism of aceclofenac; this pharmacogenomic aspect should be studied.
• Patients with lower limb venous insufficiency may also have stasis eczema that could be confused for FDE, therefore Doppler examination of the lower limbs is necessary.
• Urine culture should be done after stents on patients with high urinary pus cells and USG does not fully define renal calculi, for which CT KUB should be ordered.

8. Learning Points for Clinicians