RESIDERM February'2024 issue

Three Interesting Cases Related To Hair Case 2: Monilethrix & Case 3: Netherton Syndrome Phenytoin

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CONTENT

Three Interesting Cases Related To Hair CASE 2: MONILETHRIX

Dr. Tejasvi Patel

2nd Year Resident

Department of Dermatology, Venereology and Leprology

B.J.Medical College, Civil Hospital

Ahmedabad, Gujarat

Dr. Yashika Doshi

2nd Year Resident

Department of Dermatology, Venereology and Leprology

B.J.Medical College, Civil Hospital

Ahmedabad, Gujarat

Dr. Bela J. Shah

MD (Dermatology)

Professor & Head

Department of Dermatology, Venereology and Leprology

B.J.Medical College, Civil Hospital

Ahmedabad, Gujarat

Phenytoin Induced Toxic Epidermal Necrolysis: A Case Report

Dr.Hareesh Kumar Dasar

Junior Resident

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Department of DVL Government Erode Medical College and Hospital (GEMCH Perundurai, Erode, Tamilnaduar

Dr.K. G. Srinivasahan

Senior Resident

Department of DVL Government Erode Medical College and Hospital (GEMCH)

Perundurai, Erode, Tamilnadut up Clinic

Dr. V. Mohankumar

Associate Professor

Department of DVL Government Erode Medical College and Hospital (GEMCH)

Perundurai, Erode, Tamilnadu

Dr. Rajesh Rajagopalan

Professor and HOD

Department of DVL Government Erode Medical College and Hospital (GEMCH)

Perundurai, Erode, Tamilnadu

Three Interesting Cases Related To Hair Case 2: Monilethrix

Case 3: Netherton Syndrome

Dr. Tejasvi Patel

2nd Year Resident

Department of Dermatology, Venereology and Leprology

B.J.Medical College, Civil Hospital

Ahmedabad, Gujarat

Dr. Yashika Doshi

2ndYear Resident

Department of Dermatology, Venereology and Leprology

B.J.Medical College, Civil Hospital

Ahmedabad, Gujarat

Dr. Bela J. Shah

MD (Dermatology)

Professor & Head

Department of Dermatology, Venereology and Leprology

B.J.Medical College, Civil Hospital

Ahmedabad, Gujarat

CASE 2: MONILETHRIX

Introduction

Monilethrix is a rare hereditary condition with autosomal dominant inheritance with high penetrance and variable

expressivity. It is characterized by hair shaft dysplasia, which leads to hypotrichosis. The term “monilethrix” is derived from the Latin word “monile”

Three Interesting Cases Related To Hair Case 2: Monilethrix & Case 3: Netherton Syndrome

meaning “necklace” and the Greek word “thrix” meaning “hair.”- “Necklace hair”.1 The first case of monilethrix was described by Walter Smith in 1879 who called this condition as “a rare nodose condition of the hair”.2 The term monilethrix was given by Radcliffe Crocker. Monilethrix is usually transmitted as an autosomal dominant trait However, there are a few sporadic cases with autosomal recessive inheritance reported in the literature.3 It is a structural hair shaft disorder characterized by sparse and short hair and diffuse or patchy hair loss. The hair shaft shows a characteristic beaded or moniliform appearance due to the presence of alternate “nodes” and “internodes”. These nodes are medullated while internodes are unmedullated. These unmedullated internodes are the weak points from where hair breakage occurs due to increased fragility. Clinically, it may present with varying degrees of involvement from dystrophic hair confined only to the occiput to total alopecia. It may be associated with keratosis pilaris, leukonychia, koilonychia, dental, ophthalmic anomalies, and metabolic abnormalities.1 Here we report a rare case

of monilethrix associated with scalp psoriasis.

Case Report

A 27 year old female presented with complaint of progressive, diffuse hair loss along with thinning of hair and easy pluckability since childhood with a recent onset increase in itching and scalp scaling. The parents noticed that the hair of the scalp broke when it reaches a certain length since the age of 2 years. The hair-fall progressively increased over time with thinning of hair started from the vertex area to the present condition. History of reddish raised skin lesions over the scalp with scaling associated with itching since last 6 months. She was born out of nonconsanguineous marriage. There was no history of similar complaints in family members.

Scalp examination revealed short, sparse, dry, lusterless and fragile hairs. There were multiple, well defined erythematous scaly papules and plaques present over the scalp (Figure 1).

A developmental examination showed normal features. There were no abnormalities noted in the nail, teeth, sweat gland, eyes or other systems. Rest cutaneous examination were

also normal.

On demonstrating the auspitz sign with a pinhead, it revealed pinpoint bleeding after the removal of bulkeley’s membrane. On trichoscopic examination of scaly plaque, it showed an erythematous base with a scaly surface (Figure 2) and on examination of hair, it showed wide variation in hair-shaft diameter with uniform elliptical nodes and intermittent constrictions along with yellow dots (Figure 3). Microscopic evaluation of hair mount revealed uniform elliptical nodes with intermittent constrictions (Figure 4).

After thorough clinical and trichoscopic examination, a diagnosis of Monilethrix with scalp psoriasis was made.

The patient was counselled about the nature of the disease. She was advised to avoid sunlight, chemicals, high heat and physical trauma. The patient was treated with topical clobetasol with salicylic acid lotion for the lesions of psoriasis. The psoriatic plaques were greatly reduced while minimal regrowth of hair but hair density remained substandard.

Three Interesting Cases Related To Hair Case 2: Monilethrix & Case 3: Netherton Syndrome

of hair mount showing uniform elliptical nodes with intermittent constrictions

Discussion

Monilethrix is a rare genodermatoses with autosomal dominant inheritance. Various genetic defects have been implicated in the causation. It is caused by mutations of the genes encoding type 2 hair keratins mainly hHb1, hHb3 and hHb6.4 Mutations have been mapped to epithelial keratin gene cluster on 12q11-q13. The most common mutation is the E413K mutation in hHb6. Autosomal dominant monilethrix is caused by mutations in hair keratin genes KRT81, KRT83 or KRT86, whereas in the autosomal recessive form of this condition, mutation of the desmoglein-4 has been found.5 Due to a defect in keratin tensile strength of hair fiber decrease leads to fragile hairs. At the area of nodes, normal keratin formation occurs while at the internodal area defective keratinization occurs. In most cases of monilethrix, the hair is normal at birth; it may then be slowly replaced by abnormal hair during the first few months to two years of life. Due to increased fragility of the hair shaft, the

Figure 1: Diffuse hypotrichosis with multiple, well defined erythematous scaly papules and plaques present over scalp

Figure 2 : Trichoscopy showing erythematous base with scaly surface

Figure 3 : Trichoscopy of hair shaft showing constriction with elliptical nodes

Figure 4 : Light microscopy

Three Interesting Cases Related To Hair Case 2: Monilethrix & Case 3: Netherton Syndrome

hair fails to grow beyond a certain length giving rise to short hairs. Scalp hair is most commonly affected but in some cases, the eyelashes, eyebrows, pubic hair and/or other body hair may also be affected. In some cases, patients with monilethrix may experience remission of the disorder for no apparent reason, most often during puberty or pregnancy. In other cases, the condition may remain the same throughout life or the condition may become progressively worse. In some cases, keratosis pilaris like follicular papules were present over the scalp.6 Monilethrix is usually not associated with any systemic findings, but rare cases have been reported with trichorrhexis nodosa, mental retardation, juvenile cataracts, teeth and nail abnormalities (koilonychia), syndactyly, and metabolic abnormalities (aminoaciduria).7 In our case, we found a rare association with scalp psoriasis.

Trichoscopy is a rapid and easier diagnostic tool that shows hair shaft with alternation of nodes and constriction (internodes) with a characteristic beaded appearance. Sometimes perifollicular papules can be visualised. These findings

have been described as a “regularly bended ribbon” sign by some authors.8

Diagnosis of monilethrix can be confirmed by a light microscopic examination of the hair shaft which shows abnormal hair follicles with alternating constricted internodes and wider elliptical nodes.

Avoiding trauma remains the most effective method for the management of this condition. There is still no definitive treatment for this condition but various treatment modalities like topical minoxidil, N-acetylcysteine, retinoids and griseofulvin have shown improvement in isolated cases.9,10,11 Few cases with spontaneous resolutions were also reported.

Conclusion

The diagnosis of monilethrix was more difficult to establish in our patient due to the absence of any familial cases and associated scaling of the scalp. Trichoscopic examination along with microscopy of the hair shaft reveals the diagnosis. Here we reported an unusual association of scalp psoriasis with monilethrix.

References

1. Holani AR, Haridas NS, Shah NG, Chaudhari N. Monilethrix: a rare case diagnosed by dermoscopy. Indian

Journal of Paediatric Dermatology. 2020 Jan 1;21(1):56.

2. De Berker DA, Ferguson DJ, Dawber RP. Monilethrix: A clinicopathological illustration of a cortical defect. Br J Dermatol 1993;128:327-31

3. Arif T, Majid I, Haji IM, Samoon N. Monilethrix – Case report of a rare disease. Our Dermatol Online 2015;6:468.

4. Rakowska A, Slowinska M, Czuwara J, Olszewska M, Rudnicka L. Dermoscopy as a tool for rapid diagnosis of monilethrix. J Drugs Dermatol 2007;6:222-4

5. Farooq M, Ito M, Naito M, Shimomura Y. A case of monilethrix caused by novel compound heterozygous mutations in the desmoglein 4 (DSG4) gene. Br J Dermatol 2011;165:425-31

6. Samir MS, Chandrashekar BS, Raj RP, Shenoy C. A curious case of the necklace hair. Indian Journal of Paediatric Dermatology. 2016 Apr 1;17(2):129.

7. Hassan I, Keen A. Monilethrix: A case report. J Pak Assoc Dermatol 2012;22:169-71.

8. Tosti A, editor. Hair shaft disorders. In: Dermoscopy of Hair and Scalp: Pathological and Clinical Correlation, Illustrated Edition. USA: CRC Press; 2007. p. 51-3

9. Karincaoglu Y, Coskun BK, Seyhan ME, Bayram N. Monilethrix: Improvement with acitretin. Am J Clin Dermatol 2005;6:407-10.

10. Rossi A, Iorio A, Scali E, Fortuna MC, Mari E, Palese E, et al. Monilethrix treated with minoxidil. Int J Immunopathol Pharmacol 2011;24:239-42

11. Keipert JA. The effect of griseofulvin on hair growth in monilethrix. Med J Aust 1973;1:1236-8.

Three Interesting Cases Related To Hair Case 2: Monilethrix & Case 3: Netherton Syndrome

CASE 3: NETHERTON

SYNDROME

Introduction

Netherton syndrome is characterized by a triad of congenital ichthyosiform erythroderma or ichthyosis linearis circumflexa, hair shaft abnormalities and atopic diathesis.1 It presents at or soon after birth with generalised erythema and fine scaling of the skin that may evolve into migratory, serpiginous, erythematous patches with double-edged scales which is coined by comel as ichthyosis linearis circumflexa.2

The hair findings consist of the hallmark feature

Trichorrhexis invaginata, described by Netherton.2 Trichorrhexis nodosa, pili torti, and diffuse alopecia can be present. Features of atopic diathesis are present in some cases along with the high level of serum IgE and hypereosinophillia.3

There is a mutation in SPINK5 gene over chromosome 5q31 which encodes serine protease inhibitor LEKT1. Lack of functional LEKT1 results in increase activity of epidermal proteases causing desquamation.4

Case Report

A 4-year old male child born of a first degree consanguineous marriage

was brought by her mother with generalised erythema and scaly lesions associated with itching since infancy. The lesions began as scaling over the scalp and gradually progressed to involve the face, neck, abdomen, upper limbs, and lower limbs. Scaling was aggravated in a cold and dry climate with remission during summer and on treatment. At birth, his hair was normal, but after the age of 2 years, his mother noticed brittle hair and patchy areas of hair loss. He also had a history of recurrent episodes of rhinitis. There was also history of multiple times hospital admission for recurrent pneumonia. There was no history of similar complaints in the family. On examination, the moderately built child had generalised diffuse erythema present all over the body with multiple erythematous circinate lesions and plaques with double edged scales were seen on the forehead, trunk, hands and legs (Figure 1). The face showed diffuse erythema with scaly erythematous perioral dermatitis. DennieMorgan folds are visible below bilateral eyes which suggest the presence of atopic feature (Figure 2). Scalp examination showed

scaling with sparse, brittle, lusterless hairs with patchy non-scarring alopecia. Teeth and nails were normal. There were no remarkable changes were seen in the mucosa. The mental development of the child was normal. No other systemic involvement were noted. Complete blood evaluation was normal except peripheral smear showed eosinophilia (12%). Serum IgE level was raised (2530 IU/ml). Light microscopic examination of DPX mount of the hair showed twisting of the hair shaft (Figure 3). Scanning electron microscopy of hair shafts showed focal defects, torsional nodules and invaginated nodules (trichorrhexis invaginata) with a characteristic bamboo hair appearance (Figure 4). Biopsy from the margin of erythematous plaque over the trunk showed hyperkeratosis, parakeratosis, irregular acanthosis and spongiosis. Dermis showed lymphocytic infiltration in the perivascular areas (Figure 5). The family could not afford genetic analysis.

Based on the above features the diagnosis of Netherton syndrome was kept.

Treatment includes topical hydrocortisone (1%) lotion and emollients were given

Three

Interesting Cases Related To Hair Case 2: Monilethrix & Case 3: Netherton Syndrome

for twice daily application and Syrup Levocetrizine 2.5 ml twice daily for itching. The parents were advised to avoid scrubs, harsh soaps and multiple hot water baths and were counselled about hair growth.

Figure 1: Multiple ill-defined maculopapular plaques and patches with double edged scale present over chest, abdomen, bilateral extremities

Figure 2 : Diffuse erythema on face with perioral scaling, Dennie- Morgan fold present

Figure 3 : Twisting of hair shaft seen on light microscopic examination

Figure 4 : Characteristic bamboo hair appearance with invaginated nodules and hairshaft twisting can be appreciated

desmoglein1, leading to increased desquamation of the stratum corneum resulting in an altered skin barrier function. Also, hyperactivity of KLK5 leads to activation of nuclear factor kappa B (NF-kB) causing increased activity of tumor necrosis factor (TNF-a), interleukin-8, and thymic stromal lymphopoietin (TSLP). TSLP overexpression induces T helper type2 and T helper type 17 and increases levels of immunoglobulin E.7

compared to scalp.7 Other manifestations include atopic diathesis (atopic dermatitis, angioedema, urticaria, asthma, rhinitis and food allergies), intellectual disabilities, neurological deficits, recurrent infections, hypogamma globulinemia and hypergammaglobulinemia.8

Discussion

Netherton syndrome is a rare autosomal recessive disorder1,2 characterized by congenital erythroderma that evolves into ichthyosis linearis circumflexa, trichorrhexis nodosa, immune deficiency, hyper IgE level, and eosinophilia.1,3 Its incidence is estimated to be 1/200,000.5

There is a mutation in SPINK5 gene over chromosome 5q31 which encodes a serine protease inhibitor called lymphoepithelial Kazal-typerelated inhibitor (LEKT1). The deficiency of LEKT1 causes unrestricted activity of the epidermal serine proteases kallikrein5 (KLK 5) and kallikrein7 (KLK 7).6 KLK5 activity degrades

The clinical features of Netherton Syndrome usually begin at or soon after birth. It is present in most patient with generalised erythroderma with scaling resembling congenital ichthyosiform erythroderma that evolves to ichthyosis linearis circumflexa which has a waxing and waning course. The hair is short, scanty, weak and lustreless with patchy alopecia. The eyebrows are sparse at the lateral portion. Light microscopic examination of trichogram shows pathognomic finding Trichorrhexis invaginata also known as bamboo hair. Other findings include trichorrhexis nodosa, pili torti and helical hair. trichorrhexis invaginata is more frequently seen in eyebrow hair

Diagnosis of Netherton syndrome is usually by difficult at times due to atopic manifestations may mask the characteristic cutaneous findings, hair shaft abnormalities appears late and affects only 2050% of hairs.7 Histological findings are not specific as it usually shows psoriasiform hyperplasia. Genetic testing is necessary to confirm the diagnosis in suspicious cases.

There is no cure or satisfactory treatment available at present. Emollients are recommended to be applied twice a day after bathing. Topical corticosteroids, topical calcineurin inhibitors, topical retinoids and NBUVB (Narrowband UV B) have been used with varying success. Systemic retinoids have variable efficacy with few patients showing improvement and few facing exacerbations. Topical tacrolimus in Netherton syndrome can cause

Figure 5 : Histopathology shows parakeratosis, multilocular micro-abscess in stratum corneum and spongiosis

Three Interesting Cases Related To Hair CASE 2: MONILETHRIX & CASE 3: NETHERTON SYNDROME

elevation of its level in blood due to increased systemic absorption because of impaired barrier function, so should be use with caution.

Conclusion

In the presence of characteristic cutaneous findings, trichorrhexis invaginata, atopic diathesis, generalized erythema and elevated levels of IgE – the diagnosis of Netherton Syndrome is straightforward. However, when the features are atypical or absent, the patient may be misdiagnosed with Atopic Dermatitis. Typically, the diagnosis is delayed until the appearance of trichorrhexis invaginata which is pathognomonic. A hair examination should be carried out early so the diagnosis is neither missed nor delayed.

References

1. Boussofara L, Ghannouchi N, Ghariani N, Denguezli M, Belajouza C, Nouira R. Netherton's syndrome: the importance of eyebrow hair. Dermatology Online Journal. 2007;13(3).

2. Bopp C, Da Graça Busto M. Netherton-Comel's syndrome. Medicina Cutanea Ibero-latinoamericana. 1978 Jan 1;6(1):4559.

3. Grimbacher B, Belohradsky BH, Holland SM. Immunoglobulin E in primary immunodeficiency

diseases. Allergy. 2002 Nov;57(11):995-1007.

4. Hannula-Jouppi K, Laasanen SL, Ilander M, Furio L, Tuomiranta M, Marttila R, Jeskanen L, Häyry V, Kanerva M, Kivirikko S, Tuomi ML. Intrafamily and interfamilial phenotype variation and immature immunity in patients with Netherton syndrome and Finnish SPINK5 founder mutation. Jama dermatology. 2016 Apr 1;152(4):435-42.

5. Saleem HM, Shahid MF, Shahbaz A, Sohail A, Shahid MA, Sachmechi I. Netherton syndrome: a case report and review of literature. Cureus. 2018 Jul 30;10(7).

6. Small AM, Cordoro KM. Netherton syndrome mimicking pustular psoriasis: clinical implications and response to intravenous immunoglobulin. Pediatric Dermatology. 2016 May;33(3):e222-3.

7. Herz-Ruelas ME, ChavezAlvarez S, Garza-Chapa JI, Ocampo-Candiani J, CabMorales VA, Kubelis-López DE. Netherton Syndrome: Case Report and Review of the Literature. Skin Appendage Disorders. 2021;7(5):346-50.

8. Bellon N, Hadj-Rabia S, Moulin F, Lambe C, Lezmi G, Charbit-Henrion F, Alby C, Le Saché-de Peufeilhoux L, Leclerc-Mercier S, Hadchouel A, Steffann J. The challenging

management of a series of 43 infants with Netherton syndrome: Unexpected complications and novel mutations. British Journal of Dermatology. 2021 Mar;184(3):532-7.

Phenytoin Induced Toxic Epidermal Necrolysis: A Case Report

Dr. Hareesh Kumar Dasar

Junior Resident

Department of DVL Government Erode Medical College and Hospital (GEMCH)

Perundurai, Erode, Tamilnadu

Dr. K. G. Srinivasahan

Senior Resident

Department of DVL Government Erode Medical College and Hospital (GEMCH)

Perundurai, Erode, Tamilnadu

Dr. V. Mohankumar

Associate Professor

Department of DVL Government Erode Medical College and Hospital (GEMCH)

Perundurai, Erode, Tamilnadu

Dr. Rajesh Rajagopalan

Professor and HOD

Department of DVL Government Erode Medical College and Hospital (GEMCH)

Perundurai, Erode, Tamilnadu

Phenytoin Induced Toxic Epidermal Necrolysis: A Case Report

ABSTRACT

Toxic Epidermal Necrolysis (TEN) is a rare, but severe mucocutaneous, cellmediated hypersensitivity reaction characterized by developing extensive erythema, necrosis and detachment of epidermis and mucous membrane. It is usually induced by medications, infections or malignancy etc. Drug induced TEN is one of the most common forms of TEN and Antimicrobials have been the most commonly associated with drug induced TEN, followed by Antiepileptic drugs (AEDs) and NSAIDs. Antiepileptics such as phenytoin, carbamazepine and phenobarbital have been enlisted as high risk drugs for causing TEN. We report here a case of phenytoin induced TEN, clinical features of this condition and management of the patient are described in brief.

Keywords : Toxic epidermal necrolysis (TEN); Phenytoin; Antiepileptics; NSAIDS.

INTRODUCTION

Toxic epidermal necrolysis (TEN) is also known as "Lyell's syndrome”. It is a rare, lifethreatening dermatological condition that is usually induced by medications. Incidence of Steven

Johnson Syndrome (SJS) and TEN is approximately 1 per million populations per year.[1] It is characterized by the detachment of the dermis from the epidermis all over the body. Steven Johnson Syndrome (SJS) involves detachment of 10% or less body surface area. An overlap of SJS–TEN for cases with between 10% and 30% body surface area.[2] Both these terms are covered previously under Erythema Multiforme spectrum of diseases. But now considered as a separate entity.

TEN presents with a prodromal period, followed by poorly defined erythematous macules or diffuse ill-defined erythema. The affected skin may develop flaccid bullae and may detach irregularly, sometimes in large sheets with just a sliding touch (Nikolsky’s sign). Early sites of cutaneous involvement are the presternal region of the trunk, face, palms and soles. Involvement of the buccal, genital and/or ocular mucosa occurs in more than 90% of patients, and in some cases respiratory and gastrointestinal tracts are also affected.[3] The common causes for TEN are medications that are taken for a short period of

time, such as antibiotics co-trimoxazole, quinolones and cephalosporins or the medications used for prolonged period such as antiepileptics like phenytoin, lamotrigene, carbamazepine etc. Some rare causes are Malignancy and Idiosyncrasy. We report an interesting case of phenytoin induced TEN, details of which are given below.

CASE REPORT

A 60 year old female patient presented to the emergency ward in unconscious state with chief complaints of rashes, blisters, oral ulceration and fever. Patient had a road traffic accident 1 month back, CT Brain showed subarachnoid hemorrhage, for that as a prophylaxis she was started on Tab. Phenytoin 100 mg tds. After 15 days, she developed fever for which self-medicated with Tab. Paracetamol but with no improvement. After 2-3 days she started developing rashes and multiple clear fluid filled blisters beginning from trunk and progressing towards neck, face, back and then involving both legs over a period of 4-5 days with progressing intensity and severity along with oral ulcerations and difficulty in eating or swallowing, swelling of both lips and red

Phenytoin Induced Toxic Epidermal Necrolysis: A Case Report

swollen eyes, difficulty in opening eyes.

On physical examination, the patient had hyperpyrexia [101.1 degree celcius], blood pressure 130/70 mmHg, pulse 90bpm, respiratory rate 16cpm, chest auscultation and abdominal palpation were not significant and no lymphadenopathy, maculopapular rash present all over the body and vesicles, bullous eruptions with multiple erosions and crusting on the neck, face, trunk, back and bilateral extremities involving > 60% of body surface area with positive nikolsky sign ( figure - 1,2,3). Cheilitis , hemorrhagic crusts present over oedematous lips (figure-4). Intraoral examination showed hemorrhagic ulcerations of the vermilion surface of lips, labial and buccal mucosa, tongue and palate (figure-5). Ophthalmic examination showed acute conjunctivitis and sub conjunctival hemorrhages with mucopurulent discharge. Hemorrhagic ulcers over the eyelids and bilateral periorbital edema were also noted. Nasal mucosa showed erosions and crusting. Multiple erythematous macules and patches were present over bilateral lowerlimbs and

upperlimbs and over palms and soles with no genital involvement.

The patient was immediately admitted in septic unit with diagnosis of drug induced TEN and Tab. Phenytoin and Tab. Paracetamol were immediately stopped. She was started with Intravenous fluids (1.5 liters/day), Intravenous broad spectrum antibiotics for infections as prophylaxis, Inj. Pheniramine maleate 25 mg and Inj. Hydrocortisone100 mg tds. Oral ulcer was managed with the clotrimazole mouth paint. Ciprofloxacin eyedrops, lubricants were advised for eye lesions and saline soakes were applied twice daily gently over the skin with strict aseptic measures. The average rate of mortality was 12%, with a SCORTEN (Score of Toxic Epidermal Necrosis) score of 2. Skin biopsy done before starting the steroids which also confirmed the diagnosis.

Patient started showing improvement after 2 days of treatment, had normal body temperature with BP120/80 mm of Hg, pulse 80 beats/minute, respiration 16/minute, urinary output of 1.5-1.8 liters/day and with an overall improved general condition. Intravenous fluid was also stopped

after 1 week as patient was comfortable taking orally. Systemic steroid, Inj. Hydrocortisone stopped after tapering over 2 weeks and Tab. Prednisolone 30 mg daily started after 2 weeks. Patient recovered with remarkable regeneration of skin after 15 days and was discharged in stable condition. The patient was given an “alert card”, mentioning about various medications which were to be avoided and asked to come for follow up visits. On follow up visit after 1 week, lesions were healed (figure-7, 8, 9) and steroids were tapered accordingly.

Figure 1 : Skin lesions over upperchest

Phenytoin Induced Toxic Epidermal Necrolysis: A Case Report

Figure 2 : Skin lesions showing nikolsky sign

Figure 3 : Skin lesions over back

Figure 4 : Cheilitis, hemorrhagic crusts over oedematous lips

Figure 5 : Intraoral hemorrhagic ulcers

Figure 6 : Subepidermal bullae with widespread epidermal necrosis and subsequent separation or loss of the entire epidermis. Apoptotic keratinocytes may be seen at the periphery, Minimal inflammatory infiltrate.

Figure 7 : Healed lesions of lips

Figure 8 : Healed lesions over back

Figure 9 : Healed lesions of upperchest

Phenytoin Induced Toxic Epidermal Necrolysis: A Case Report

DISCUSSION

Toxic epidermal necrolysis (TEN) is also known as "Lyell's syndrome”. By Rooks definition, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, usually to drugs, characterized by blistering and epithelial sloughing. These two terms describe the phenotypes within a severity spectrum, in which SJS is the less extensive form and TEN is more extensive. Both names are used to describe the syndrome, thus: SJS/TEN. Incidence of TEN is 1-2 cases per million per year [In India, 0.9–1.4 per million per year] in the general population, occurs in all age groups including infants and children, but most common in elderly people. Increased incidence is seen among women. Increased risk of TEN seen in HIV infected individuals and in SLE patients.

It is usually induced by medications, infections or malignancy etc. Drug induced TEN is one of the most common forms of TEN and Antimicrobials (37.27%) have been the most commonly associated with drug induced TEN, followed by Anti-epileptic drugs (AEDs) (35.73%) and NSAIDs (15.93%).

[4] Anti-epileptics such as phenytoin, carbamazepine and phenobarbital are the high risk drugs for causing TEN. Phenytoin induced TEN can occur at any time between 2 and 8 weeks after initiation of the treatment and may progress despite discontinuation of the drug. Factors associated with increased risk of this reaction include the use of higher than recommended dose, more rapid dose escalation and concomitant use of valproate. Pathophysiology of the phenytoin induced TEN is idiosyncratic, may involve hypersensitivity due to toxic metabolites of suspected drug/s. Arene oxides derived from aromatic antiepileptics such as phenytoin, carbamazepine etc, bind to cell constituents if they are not rapidly detoxified by epoxide hydrolase. These metabolites act as haptens and render the keratinocytes antigenic by binding to them.[5] Genetic basis for SJS/TEN have been attributed to inherited or acquired deficiency in phase 2 detoxification enzymes or from an elevated cytochrome P450 (CYP 450) isoform (s). Few studies have also indicated an association between HLA*1502 and phenytoin induced SJS/ TEN.[6] Family history of such reactions should always be

asked by the prescribing doctor before prescribing these medicines.

TEN is characterized by prodromal phase of 1–14 days with Flu-like symptoms such as discomfort, pain, fever, sore throat, cough, malaise and inflammation of eyelids, conjunctiva and oral mucosa also seen. Followed by generalised macular erythema which progresses to appearance of flaccid blisters and bullae, join to form large bullae. Large areas of epidermis are “sloughed off”. Mucous membranes are involved usually 1-3 days earlier than skin lesions such as eyes; oropharynx; respiratory tract; gastrointestinal tract; genital tract; anus. Rapid progression seen over days and 10–100% of body’s surface area are involved.

Differential diagnosis are pemphigus vulgaris, erythema multiforme major, mucous membrane pemphigoid, bullous pemphigoid, burns, conjunctivitis , ulcerative keratitis, staphylococal scalded skin syndrome, exfoliative dermatitis etc.

Complications of TEN are conjunctivitis, vesiculation, corneal ulceration/ scarring, uveitis, synchiae, pseudomembrane formation, blindness;

Phenytoin Induced Toxic Epidermal Necrolysis: A Case Report

scarring, hypopigmentation and hyperpigmentation of skin; scarring of mucous membranes, oesophageal, bronchial, anal and vaginal strictures are also commonly seen.

Management of TEN is mainly supportive. As multidisciplinary approach is needed, patient should be managed in Burns unit/ ICU. At first causative drug should be discontinued. Skin care and barrier nursing is needed to protect the skin from infections. Monitor fluid and electrolyte balance. Nutritional support, analgesics (may need oral/ iv morphine) should be given. Eyes should be taken care with lubrications and antibiotics. Many drugs are implicated in the prevention of progression of this condition like systemic steroids, intravenous immunoglobulin and cyclosporine A, cyclophosphamide and TNF antagonists etc.[7] In our patient however, intravenous steroids along with antibiotics were used for treatment of infective lesions on the skin might have led to the recovery of the patient.

CONCLUSION

We present this case, for its rare occurrence, the drug Phenytoin involved

in causing the toxic epidermal necrosis. Before starting treatment with anticonvulsants and other drugs, patients should be screened first, so that the medications which are potent to cause adverse drug reactions could be avoided, so that further complications and mortality can be reduced. It is also advisable to give “drug alert card”- to the patient who suffered from such serious reactions.

REFERENCES

1. Vesiculobullous disorders; Valia AR et al. IADVL Textbook and Atlas of Dermatology 2nd ed. 2001; 857-905.

2. Phenytoin induced toxic epidermal necrolysis : A Case Report; Bandaru Sheshagiri Sharvana bhava et al. Open J Clin Med Case Rep : 2018|Vol 4|Issue 13.

3. Pulmonary complications in toxic epidermal necrolysis: a prospective clinical study; Lebargy F, Wolkenstein P, Gisselbrecht M et al; Intensive Care Med.1997;23:123744.

4. Phenytoin induced Stevens-Johnson syndrome in a 38 year male patient : A Case Report; Sukhpreet Singh et al; International Archives of BioMedical and Clinical Research|July-Sept 2015|Vol 1|Issue 1.

5. Phenytoin Induced Steven Johnson Syndrome;

Inamdar et al; Indian Journal of Pharmacy Practice; OctDec, 2020|Vol13|Issue 4;

6. Phenytoin induced toxic epidermal necrolysis : A Case Report; Rima Shah et al; International Journal of Medical Science and Public Health; 2013|Vol 2| Issue 3

7. Phenytoin induced toxic epidermal necrolysis; AlQuteimat et al; Journal of Pharmacology and Pharmacotherapeutics ; July-September 2016|Vol 7| Issue 3