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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 8  |  Issue : 2  |  Page : 86-88

Concomitant Nicolau’s and Stevens-Johnson syndrome—Toxic epidermal necrolysis overlap after diphtheria, pertussis, tetanus vaccination: An unusual presentation in a young child


Department of Dermatology, Venereology and Leprosy, Vijayanagar Institute of Medical Sciences (VIMS), Ballari, Karnataka, India

Date of Submission28-Jun-2021
Date of Decision22-Sep-2022
Date of Acceptance29-Nov-2022
Date of Web Publication5-Jan-2023

Correspondence Address:
Sambasiviah C Murthy
Department of Dermatology, Venereology and Leprosy, Vijayanagar Institute of Medical Sciences (VIMS), Ballari-583104, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_28_21

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  Abstract 

Diphtheria, pertussis, tetanus (DPT) is a live attenuated vaccine included in the national immunization schedule. Common adverse effects of this vaccine include localized pain, erythema, and high-grade fever. Rarely, it can cause severe localized or generalized reactions such as Nicolau’s syndrome (NS), erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). A 6-year-old boy developed severe pain over left gluteal region, immediately after DPT vaccine, followed by local ulceration. Two days later, he also developed mucocutaneous lesions. Clinical features were consistent with NS and SJS-TEN overlap. Concomitant NS with SJS-TEN overlap after DPT vaccine is rare and has not been reported earlier.

Keywords: DPT vaccine, embolia cutis medicamentosa, immunization, injection site reaction, severe cutaneous adverse reactions


How to cite this article:
Murthy SC, Hande M, Gudi SD, Sagri UF. Concomitant Nicolau’s and Stevens-Johnson syndrome—Toxic epidermal necrolysis overlap after diphtheria, pertussis, tetanus vaccination: An unusual presentation in a young child. Indian J Drugs Dermatol 2022;8:86-8

How to cite this URL:
Murthy SC, Hande M, Gudi SD, Sagri UF. Concomitant Nicolau’s and Stevens-Johnson syndrome—Toxic epidermal necrolysis overlap after diphtheria, pertussis, tetanus vaccination: An unusual presentation in a young child. Indian J Drugs Dermatol [serial online] 2022 [cited 2023 Feb 8];8:86-8. Available from: https://www.ijdd.in/text.asp?2022/8/2/86/367121




  Introduction Top


Vaccines are important for the prevention of infectious diseases; however, they may cause cutaneous side effects. Some of these reactions are due to nonspecific inflammation and irritation at the injection site, while others can be associated with generalized hypersensitivity reactions, such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), urticaria, etc.[1]

Nicolau’s syndrome (NS), also called as embolia cutis medicamentosa or livedoid dermatitis, is a rare localized cutaneous reaction caused by intramuscular injection of certain drugs and vaccines. The severity of damage can range from ulceration to muscular necrosis.[2]

EM, SJS, and toxic epidermal necrolysis (TEN) are cutaneous hypersensitivity reactions in the same clinical spectrum. EM may be minor, without mucosal involvement and major involving more than two mucosae.[2] SJS and TEN are characterized by widespread epidermal necrosis of skin and mucosa. They are classified based on the severity of epidermal detachment; SJS involves less than 10%, SJS-TEN overlap, 10%–30%, and TEN more than 30% of body surface area.[3],[4]

NS and SJS-TEN are rarely caused by vaccines. We describe an unusual, concomitant occurrence of NS and SJS-TEN overlap, after intramuscular administration of diphtheria, pertussis, tetanus (DPT) vaccine.


  Case Report Top


A 6-year-old boy presented with fever, painful ulceration over left gluteal region, skin rash, painful oral and genital lesions for the last 4 days, following administration of DPT vaccine. Child had severe pain over the injection site immediately after the administration. Over the next two days, mother noted redness and ulceration at the site of injection. She also noted multiple, red to brownish flat lesions that appeared 2 days later over the upper and lower limbs, palms, soles, and trunk. Painful oral and genital lesions with redness and matting of eyes were seen. Prior drug intake or systemic illnesses were lacking. His family and past history were unremarkable.

Cutaneous examination showed a solitary, well-defined, oval, nonindurated, tender, ulcer of about 6 × 5 cm over the left gluteal region [Figure 1]. Multiple, discrete, purpuric macules over trunk, back, chest, extremities, palms, and soles [Figure 2] were seen with occasional epidermal detachment and pseudo-Nikolsky sign. Hemorrhagic crusts involving both upper and lower lips, with multiple superficial tender erosions over the palate and buccal mucosae were noted. Erosions were seen over the preputial skin with ocular congestion. There was no lymphadenopathy, and systemic examinations were normal.
Figure 1: Ulcer over left gluteal region

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Figure 2: Purpuric macules over trunk, upper and lower limbs, and lip crusting

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Routine hematological, biochemical, and urine examinations were normal. Antistreptolysin O titre, serology for human immunodeficiency virus, and hepatitis B virus were normal or negative. Chest X-ray did not show any radiological abnormality. The child was started on intravenous fluids, dexamethasone 8 mg daily for initial 5 days followed by 4 mg daily for 7 days, amikacin and amoxiclav, in consultation with a pediatrician. Sterile dressing of the ulcer was done every alternate day. Mucocutaneous lesions healed by 3 weeks, while ulcer on the gluteal region healed with atrophic scarring in 5 weeks. A diagnosis of DPT-induced NS and SJS-TEN overlap was made based on the clinical features and course.


  Discussion Top


NS is a rare injection-site reaction initially recognized as an adverse effect of bismuth salts used in syphilis. It was first described by Freudenthal and Nicolau in 1924 and 1925 respectively.[5] Several mechanisms have been postulated in the pathogenesis of NS. Intra-arterial or periarterial injection of the offending agent resulting in direct trauma or arterial embolism or compression of the artery is one of the mechanisms. Arterial vasospasm secondary to intra-arterial penetration of drug resulting in livedoid necrosis is the other possible mechanism.[6] Children younger than 3 years have smaller vascular segments and therefore, arterial embolism is more likely.[7] Pyrazolone derivates, diclofenac, glucocorticoids, ibuprofen, vitamin B complex, antibiotics, recombinant interferon, and a mixture of sedatives are reported medications incriminated in NS. Antibiotics are identified to be the most common cause of NS in children.[2]

Vaccine is a rare cause of NS in children; only a few cases are reported in association with DPT vaccine.[2] NS is characterized by immediate pain, followed by swelling within the first few hours. One to 3 days later, an acute phase characterized by an indurated, tender plaque with livedoid pattern develops. Necrotic areas and ulceration may develop 5 days to 2 weeks later.[8] Extent and depth of tissue involvement can vary; it can be cutaneous, subcutaneous, and muscular.[5] In our case, immediate pain after injection, development of redness, and subsequent ulceration over the same site were the features suggestive of NS, unlike SJS, which occurs, with widespread lesions (atypical targets/purpuric macules/blistering on purpuric macules) a few hours to days after the injection, unrelated to the injection site.

In our case, superficial ulceration, with only cutaneous involvement was seen. Conservative treatment with dressings, debridement, and pain control is the mainstay of therapy. Intralesional corticosteroids to reduce local inflammation, vasoactive medications like pentoxyphylline and heparin may also be beneficial.[5] Systemic antimicrobials may also be administered to prevent secondary infection.[1]

SJS was first described by Stevens and Johnson in 1922. In 1956, Lyell used the term TEN to describe the chafed-looking skin lesions in his patients and considered it to be toxin-induced. SJS and TEN are considered to be variants of the same pathologic process. Drugs are implicated in the majority of adults and children with SJS-TEN. Other triggers include mycoplasma pneumoniae, herpes simplex virus, streptococci, cytomegalovirus, and vaccines[3]

Vaccination-induced SJS-TEN is rare. Immunologic theory is the accepted pathogenic mechanism for vaccine-induced cutaneous hypersensitivity. Antigen in the vaccine is expressed on the surface of keratinocytes, generating a CD8+ T lymphocyte immune response against epidermal cells (Type IV hypersensitivity). This leads to apoptosis of keratinocytes and detachment at the dermal-epidermal junction. This process is not immediate, explaining the typical 3–5-day latency period. Preservatives and fixatives in vaccines, such as aluminium, thimerosal, formaldehyde, cellular pertussis vaccine in DPT, are implicated as triggering agents. Initial morphologies of SJS-TEN following vaccination appear to fall into three general categories: macular, vesicular, and targetoid (EM-like).

Treatment options for vaccine-induced TEN include plasmapheresis, IVIG, and perhaps most promisingly, TNF inhibitors such as etanercept.[9] Mortality is substantially higher in TEN.[4] Our patient initially developed purpuric macules, which progressed to involve 10%–30% area, with occasional epidermal detachment consistent with SJS-TEN overlap and responded to intravenous steroids and conservative management.

Although, vaccine-induced EMF has been reported in about 19 pediatric patients, which includes DPT vaccine (seven case reports), there are no case reports of DPT-induced SJS-TEN.[9] Risk of recurrence should be taken into account with respect to the future administration of DPT vaccine.[10] This report highlights an uncommon adverse effect of a commonly used vaccine. Although NS due to DPT is well established, the concomitant occurrence of NS and SJS-TEN overlap has not been reported, to the best of our knowledge. Caution during administration, awareness and early recognition helps in appropriate management of conditions, thereby reducing morbidity and mortality.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rosenblatt AE, Stein SL Cutaneous reactions to vaccinations. Clin Dermatol 2015;33:327-32.  Back to cited text no. 1
    
2.
Kienast AK, Mentze D, Hoeger PH Nicolau’s syndrome induced by intramuscular vaccinations in children: Report of seven patients and review of the literature. Clin Exp Dermatol 2008;33:555-8.  Back to cited text no. 2
    
3.
Das S, Ramamoorthy R Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Indian J Paediatr Dermatol 2018;19:9-14.  Back to cited text no. 3
    
4.
Callahan SW, Oza VS Stevens-Johnson syndrome: A look back. JAMA Dermatol 2017;153:240.  Back to cited text no. 4
    
5.
Murthy SC, Siddalingappa K, Suresh T Nicolau’s syndrome following diclofenac administration: A report of two cases. Indian J Dermatol Venereol Leprol 2007;73:429-31.  Back to cited text no. 5
    
6.
Erkek E, Tuncez F, Sanli C, Duman D, Kurtipek GS, Bagci Y, et al. Nicolau’s syndrome in a newborn caused by triple DTP (diphtheria-tetanus-pertussis) vaccination. J Am Acad Dermatol2006;54(5 Suppl):S241-2.  Back to cited text no. 6
    
7.
Zahra FT, Amin SS, Adil M, Alam M Nicolau syndrome in a neonate. Indian J Paediatr Dermatol 2019;20:284-5.  Back to cited text no. 7
    
8.
Adil M, Amin SS, Arif T Nicolau’s syndrome: A rare but preventable iatrogenic disease. Acta Dermatovenerol Croat 2017;25:251-3.  Back to cited text no. 8
    
9.
Chahal D, Aleshin M, Turegano M, Chiu M, Worswick S Vaccine-induced toxic epidermal necrolysis: A case and systematic review. Dermatol Online J 2018;24:1-10.  Back to cited text no. 9
    
10.
Frederiksen MS, Brenøe E, Trier J Erythema multiforme minor following vaccination with paediatric vaccines. Scand J Infect Dis 2004;36:154-5.  Back to cited text no. 10
    


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