A Challenging Case of Toxic Epidermal Necrolysis in a 2 Year Old Child With Review of Literature

Gautam Kumar Singh; Barnali Mitra; Ajay Chopra; Ashwin Arora; G Prashantha

doi:10.4103/ijpd.IJPD_64_20

CASE REPORT

Year : 2021 | Volume : 22 | Issue : 1 | Page : 62-65

A Challenging Case of Toxic Epidermal Necrolysis in a 2 Year Old Child With Review of Literature

Gautam Kumar Singh¹, Barnali Mitra², Ajay Chopra¹, Ashwin Arora³, G Prashantha⁴
¹ Department of Dermatology, Venereology and Leprosy, Army College of Medical Sciences, Delhi, India
² Department of Paediatrics, Army College of Medical Sciences, Delhi, India
³ Base Hospital Delhi Cantt, Delhi, India
⁴ DNB Resident, Base Hospital Delhi Cantt, Army College of Medical Sciences, Delhi, India

Date of Submission	20-Apr-2020
Date of Decision	07-May-2020
Date of Acceptance	04-Jun-2020
Date of Web Publication	31-Dec-2020

Correspondence Address:
Barnali Mitra
Associate Prof, Department of Paediatric, Base Hospital Delhi Cantt & Army College of Medical science, Delhi - 110 010
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijpd.IJPD_64_20

Abstract

Toxic epidermal necrolysis (TEN) is a rare, severe, life-threatening, mucocutaneous adverse drug reaction characterized by widespread blistering and sloughing of the epidermis and mucositis with fatal complications such as sepsis and multiorgan failure. In most cases, drugs are implicated, but occasionally, vaccination and infection can be the triggers of TEN. TEN is very rare in infants and young children and usually has a fatal outcome due to sepsis or multiorgan failure due to large body surface area. Till now, only a few reports have been documented in the literature. We hereby report a challenging case of TEN in a 2-year-old boy who had had a turbulent course during his hospital admission. He was successfully treated with intravenous immunoglobulin followed by systemic steroid along with high-end systemic antibiotics in a dedicated dermatology intensive care setup taking care of his fluid, electrolytes, calories, protein demand, and care of skin and mucosa.

Keywords: Intravenous immunoglobulins, Stevens–Johnson syndrome, systemic corticosteroid, toxic epidermal necrolysis

How to cite this article:
Singh GK, Mitra B, Chopra A, Arora A, Prashantha G. A Challenging Case of Toxic Epidermal Necrolysis in a 2 Year Old Child With Review of Literature. Indian J Paediatr Dermatol 2021;22:62-5

How to cite this URL:
Singh GK, Mitra B, Chopra A, Arora A, Prashantha G. A Challenging Case of Toxic Epidermal Necrolysis in a 2 Year Old Child With Review of Literature. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Jan 15];22:62-5. Available from: https://www.ijpd.in/text.asp?2021/22/1/62/305814

Introduction

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe mucocutaneous reactions, mostly to drugs occasionally to infections, characterized by blistering and epithelial sloughing. It is a spectral disease where TEN is more serious and extensive, with involvement of more than 30% body surface area.^[1] Even though pathogenesis is uncertain, there is widespread epithelial keratinocyte necrosis of skin and mucosa, a process initiated by drug-induced cytotoxic T-lymphocytes along with other proapoptotic molecules such as tumor necrosis factor-α, interferon-γ, and inducible nitric oxide synthase, soluble Fas ligand, perforin, and granzyme.^[2],[3] There are very few large-scale retrospective studies of TEN in the pediatric population.^[4],[5] An extensive literature search revealed that severe cutaneous drug reactions are extremely rare in children below 5 years of age.^{[6],[7],[8],[9],[10],[11],[12],[13]} Our case is unique with turbulent course in the hospital which is being reported for its rarity and challenges faced during its management.

Case Report

A 2-year-old boy presented with fever of 12 days duration and multiple fluid-filled lesions and erosions over the body of 3-day duration along with cough and sore throat. Temporal drug profile revealed that he had received syrup paracetamol, paracetamol with diclofenac sodium combination, followed by cefixime, chloroquine, pyrimethamine plus sulfadoxine combination over last 7 days, and then syrup Septran® (sulfamethoxazole and trimethoprim combination) for 4 days. On the 10^th day of fever, the child developed redness over the lips, eyes, and genitalia which rapidly progressed to involve other parts of the body. Examination revealed a sick looking, febrile, irritable child having a temperature of 101.3°F, tachycardia (pulse – 148/min), and tachypnea (respiratory rate – 30/min) with normal oxygen saturation. Dermatological examination revealed multiple, polysized, purpuric vesicles and bullae, and at places, these bullae had coalesced to form larger bullae or sheets of skin erosion distributed over the scalp, face, trunk, and extremities. Nikolsky's sign was positive. There were hemorrhagic crusts on the lips, eyelids were adhered together with ocular discharge, and genitalia and perineal areas showed sheet-like erosions [Figure 1]a,[Figure 1]b,[Figure 1]c,[Figure 1]d. There was conjunctival congestion but no corneal damage. His SCORTEN was 2. Based on his history, clinical examination, and notoriety of the drug, he was diagnosed as a case of TEN due to Septran® (co-trimoxazole plus trimethoprim).

Figure 1: Clinical image of the patient on day 1 of the admission; (a) Multiple, discrete as well confluent purpuric bullae, erosions over the chest, scalp, and face, and hemorrhagic crusts on the lips; (b and c) Similar purpuric bullae and erosions over the trunk; (d) A large, coalesced, similar looking bullae over the shaft of the penis causing sheet-like erosions along with purpuric bullae and erosions in the genital and perineal areas

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All his previous drugs were stopped forthwith, and he was admitted in a specialized dermatology intensive care unit setup, where ambient temperature was maintained at 30°C–32°C and double barrier nursing facility was used. Fluid (2 ml/kg/body surface area), calories (1400 kcal/d), and high protein diet were provided along with care of skin and mucosa. He was administered intravenous immunoglobulins (IVIGs) in the dosage of 2 g/kg with a total cumulative dose of total 20 g over 3 days. He continued to develop new bullae and erosions even after finishing of IVIG dosage over the next 7 days. Later, after 3 days of IVIG dosage, injection dexamethasone was added in dosage of 0.6 mg/kg in two divided dosages for 7 days along with systemic ceftriaxone. Denuded skin was covered with silver-impregnated dressing (Acticoat®). Erosions over the neck and genitals were kept open, cleaned with potassium permanganate compresses, followed by application of 2% mupirocin ointment.

Initial investigations revealed an hemoglobin (Hb) of 9.2 g%, with thrombocytosis (4.5 × 10⁶ cells/mm³), and raised C-reactive protein. Consent for skin biopsy was not given by the parents. As the diagnosis of TEN was evident clinically and a skin biopsy would not have added any other diagnostic or prognostic value, so it was not forced on by the treating team. He was extensively evaluated for continuing fever with following tests: liver and renal function, tests for malarial parasites (slides for malarial parasite, Paracheck), enteric fever (typhidot, widal), dengue serology, other viral markers (HIV, hepatitis B surface antigen, and anti-hepatitis C virus antibodies), antinuclear antibody, blood culture, routine urine examination, urine culture, swabs from denuded skin areas, and chest X-ray posteroanterior view. His entire workup did not yield any positive report.

He had a very turbulent course in the hospital. His skin and mucosal lesions progressively increased to involve almost 80% of body surface areas by the end of the 1^st week [Figure 2]a,[Figure 2]b,[Figure 2]c,[Figure 2]d, with a SCORTEN of 3.

Figure 2: Clinical image of the patient on day 7 of the hospitalization. Widespread areas of sheet-like erosions and raw surface over the face (a); Front of the body (b); Back of the body (c) and genitalia (d) Nikolsky's sign was positive

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At the end of the 2^nd week of hospitalization, his skin lesions had stopped progressing, however, he continued to have fever. He developed leukocytosis with total leucocyte count of 18,300/cmm with neutrophilia of 91%, shift to the left and toxic granules on peripheral blood smear. He lost weight (10 kg–8.3 kg); Hb dropped to 4.8 g%, albumin lowered to 1.4 g/dl and he developed hypomagnesemia. Additional tests such as two-dimensional echocardiography, ultrasound abdomen, repeated blood culture, urine culture, skin swab for culture, or chest X-ray were conducted to search for any focus of infection but were not contributory. He was administered packed red blood cell transfusion and injection albumin and amino acid and other supplements in consultation with a pediatrician. His antibiotics were upgraded to injection teicoplanin and meropenem. At the end of 3 weeks of hospitalization, he became afebrile for 3 days but developed fever again. He had now oral candidiasis, urine culture revealed Escherichia ^{More Details} coli sensitive to tigecycline, and skin swab from the gluteal region showed growth of Pseudomonas sensitive to amikacin. His antibiotic regimen was changed to tigecycline and injection amikacin, and systemic fluconazole was also added. He became afebrile and clinically better at the end of the 3^rd week of hospitalization [Figure 3]a,[Figure 3]b,[Figure 3]c,[Figure 3]d. He was discharged after 4 weeks of hospitalization with advice not to take Septran (co-trimoxazole plus trimethoprim) or any other sulfa group of drugs in the future. He was asked to get reviewed from the dermatology and eye outpatient department.

Figure 3: Clinical image of the patient on day 21 of the hospitalization. Preexisting raw areas have started resolving with scaling and postinflammatory hypopigmentation on the face and trunk (a) and extremities (b)

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Discussion

Drugs such as antibiotics (sulfonamides and beta-lactam), anticonvulsants (phenytoin, phenobarbital, and carbamazepine), antiretroviral (nevirapine and abacavir), nonsteroidal anti-inflammatory drugs (oxicams), and allopurinol are the most common offender of SJS/TEN, especially in children. Despite the best efforts, the offending drug history is not elicited in about 15% of cases, and in these cases, other triggers such as vaccination and infections, most notably by Mycoplasma pneumoniae, are suspected.^[1]

Diagnosis of TEN is clinical, and the notoriety of drug along with temporal profile of drugs helps in identifying the culprit drug. The closest differential diagnosis, especially in neonates and infants, is staphylococcal scalded skin syndrome (SSSS). Unlike TEN, blistering in SSSS is very superficial without purpuric appearance, more on frictional sites without any mucosal involvement.

Our child had a very progressive course and extensive disease. A trained nurse under supervision of a pediatric intensivist handled placing of intravenous line, peripherally inserted central catheter line, tying sphygmomanometer cuff, calculation of daily fluid, electrolytes, calories and protein requirements. In addition to soft white paraffin and mupirocin ointment, silver-impregnated dressing (Acticoat®) was applied on denuded skin to avoid daily skin dressing changes. There is a lack of proper evidences in the specific therapies of SJS/TEN due to ethical concerns and rarity of the condition. Nevertheless, systemic corticosteroids, IVIG, cyclosporine, cyclophosphamide, thalidomide, and plasmapheresis have been tried with variable outcome.^[1],[7],[14] Even large studies did not find any benefit from corticosteroids or IVIG or both combined when compared to supportive therapy.^[15],[16]

The role of systemic steroid has been controversial having beneficial^{[17],[18],[19]} as well as detrimental^[20] effects. We had to administer injection dexamethasone to our patient when his progression of epithelial damage did not stop by IVIG. He had substantial clinical improvement with systemic corticosteroids. Theoretically, cyclosporine is the drug which should have the best efficacy in SJS/TEN considering its role in inhibition of lymphocyte function which is key in SJS/TEN pathogenesis. In a study by Singh et al., cyclosporine group had shown significantly enhanced speed of epithelialization, a reduced length of hospital stay, and a benefit in SCORTEN-predicted mortality in comparison to systemic steroid retrospectively.^[21] However, the report of its usage in a pediatric case is very limited.

Conclusion

The SJS/TEN is life threatening condition. The fundamental principle in the management of SJS/TEN is withdrawal of the culprit drug, multidisciplinary consultations, meticulous care of lesional skin, mucosa, coupled with care for the systemic complications of acute skin failure in intensive care setup for excellent outcome. There is no harm in giving a trial of systemic steroid if the progression of the disease is not stopped even after IVIG.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

We would like to thank the Paediatricians and Ophthalmologists, Base Hospital Delhi Cantt, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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