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\begin{document}

\title{Recurrent Toxic Epidermal Necrolysis (TEN) with different drugs}



\author[1]{Mahesh Mathur}%
\author[1]{Neha Thakur}%
\author[1]{Sunil Jaiswal}%
\author[1]{Srijana Maharjan}%
\author[1]{Supriya Paudel}%
\author[1]{Anjali Shrestha}%
\affil[1]{College of Medical Sciences Teaching Hospital}%


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  \date{May 18, 2024}


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\textbf{Title of the paper}

\textbf{RECURRENT TOXIC EPIDERMAL NECROLYSIS (TEN) WITH DIFFERENT DRUGS}

\textbf{Introduction}

Toxic Epidermal Necrolysis (TEN) is a life-threatening mucocutaneous
disorder characterized by diffuse erythema, necrosis, and flaccid bulla
involving Body Surface Area (BSA) \emph{\textgreater{}} 30\% and
resulting in desquamation. The incidence of TEN is 1-2/1000000 annually.
Majority of the cases of TEN are
drug-induced.\textsuperscript{1}Recurrent episodes are rare in adults,
however, reported more frequently in the pediatric
population.\textsuperscript{2} We hereby present a case of recurrent TEN
in an elderly patient with different agents.

\textbf{Case Presentation}

A 60-year-old female, a known case of Hypertension and Chronic Kidney
Disease presented to Emergency Department with generalized ill-defined
confluent dusky erythematous tender patches and flaccid bullae on the
trunk and extremities with peeling of skin over the mammary region for 3
days (fig 1D-F). She had erosions on lips, hard palate, and mucopurulent
discharge from the eyes. Skin lesions developed after 16 hours of intake
of the last dose of Furosemide as advised by the treating physician for
facial puffiness and pedal edema.

Nikolsky's sign was positive. Body Surface Area involved was
approximately 40\% and she was hemodynamically stable. Blood
investigations revealed raised Serum BUN (106.6 mg/dl), raised
creatinine (4.6 mg/dl), and hypokalemia (2.9 meq/l). Arterial Blood Gas
analysis showed decreased pH (7.24) and bicarbonate levels (12meq/l).

Diagnosis of TEN with Acute on Chronic Kidney Disease and Metabolic
Acidosis was made with baseline SCORTEN 5. She was admitted to ICU and
was administered intravenous fluids, antibiotics, and parenteral
hydrocortisone along with mucocutaneous care. SCORTEN was 5 on the
3\textsuperscript{rd} day of admission. Initial reepithelialization of
skin lesion was observed after 7 days (fig 2A-C) and was completed by
Day 15 (fig. 2D-F).

The patient had a similar episode of skin lesions 3 years back following
intake of Nimesulide for myalgia and developed extensive mucocutaneous
lesions as compared to the second episode (fig. 1A-C). She was admitted
to our hospital during the previous episode and was managed
successfully.

\textbf{Discussion}

TEN is a dermatological emergency mediated predominantly by CD8+ T
lymphocytes and is associated with an average mortality of
25\%.\textsuperscript{2,3} Patients carrying susceptible specific
haplotypes, cross-reactivity between the drugs with very similar
stereochemical structures, and drug metabolites generated by the
Cytochrome P450 enzyme complex may influence the recurrence of SJS
and/or TEN.\textsuperscript{2}

Our patient had 2 episodes of TEN following intake of Furosemide at
present and Nimesulide 3 years back. Literature search revealed a
similar chemical structure in Nimesulide and Furosemide as both the drug
molecule contains the sulfonamide functional group
(R-S(=O)~\textsubscript{2}-NR~\textsubscript{2}) which might have
triggered the second episode in our patient.\textsuperscript{4,5} In our
patient, the skin lesions in the second episode of TEN appeared earlier
as compared to the usual duration reported in the literature. The cause
of the short latency period may be attributed to the sensitization of
the patient to the sulfonamide group of drugs in the first episode. Our
patient lacked constitutional symptoms and mucocutaneous involvement was
less severe as compared to the first episode which might be due to the
early presentation of the patient to our center along with early
therapeutic intervention.

\textbf{Conclusion}

Conventionally, Nimesulide and Furosemide are two different groups of
drugs but an intense literature search revealed that both drugs have a
common sulfonamide functional group which triggered the subsequent
episode of TEN. Thus, it is important to note that any patient who has
had a previous hypersensitivity reaction to a drug is at high risk for
recurrence with another drug having a similar chemical structure, and
treating physicians should always consider cross-reactivity between the
chosen drugs in order to prevent the subsequent life-threatening
clinical episodes.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Harr T, French, LE. Toxic epidermal necrolysis and Stevens-Johnson
  syndrome.~Orphanet J Rare Dis.2010;\textbf{5} (39):1-11.
\item
  Drateln CR, Gomez-Hernandez N, Martinez NR, Torres-Lozano C. Recurrent
  Toxic Epidermal Necrolysis Syndrome: A Report of Two Cases. Drug Saf
  Case Rep.2016;3(9):1-4.
\item
  Kinoshita Y, Saeki H. A Review of the Pathogenesis of Toxic Epidermal
  Necrolysis. J Nippon Med Sch. 2016;83(6):216-222.
\item
  National Center for Biotechnology Information. PubChem Compound
  Summary for CID 4495, Nimesulide{[}Internet{]}.US:NLM;{[}cited 2023
  July 11{]}. Available
  from:https://pubchem.ncbi.nih.gov/compound/Nimesulide
\item
  National Center for Biotechnology Information. PubChem Compound
  Summary for CID 3440, Furosemide{[}Internet{]}.US:NLM;{[}cited 2023
  July 10{]}. Available
  from:https://pubchem.ncbi.nih.gov/compound/Furosemide
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