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Case Reports in Infectious Diseases

Volume 2019, Article ID 5471765, 5 pages
https://doi.org/10.1155/2019/5471765

Case Report
A Case Study of Stevens–Johnson Syndrome-Toxic Epidermal
Necrolysis (SJS-TEN) Overlap in Mycoplasma pneumoniae-
Associated Tracheobronchitis

Ranjit Sah ,1,2 Samikshya Neupane,3 Shusila Khadka,1 Sagar Poudyal,4 Hem Raj Paneru,5
Ranjana Sah,4 Sanjit Sah,4 and Vivek Pant4
1
Department of Microbiology, Thribuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Nepal
2
Department of Medicine (Division of Infectious Disease), Medanta-The Medicity, Gurugoan, Haryana, India
3
Department of Pathology, Thribuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Nepal
4
Institute of Medicine, Tribhuvan University, Kathmandu, Nepal
5
Department of Anesthesia (Critical Care), Thribuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Nepal

Correspondence should be addressed to Ranjit Sah; ranjitsah57@gmail.com

Received 7 December 2018; Accepted 20 May 2019; Published 30 May 2019

Academic Editor: Tomoyuki Shibata

Copyright © 2019 Ranjit Sah et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Stevens–Johnson syndrome is a medical emergency which is characterized by skin and mucosal reaction to the use of certain drugs.
Atypical Steven–Johnson syndrome can occur due to various microorganisms and Mycoplasma pneumoniae being one of them. We
present a clinical course, diagnosis, and successful management of Steven–Johnson syndrome-toxic epidermal necrolysis (SJS-TEN)
overlap due to Mycoplasma pneumoniae in a 17-year-old Nepalese female. In the resource-limiting country and hospitals where
serology and PCR for M. pneumoniae is not easily accessible, a simple bedside cold agglutination test can be done to increase the
suspicion of infectious cause (most common M. pneumoniae ) of SJS-TEN overlap. M. pneumoniae infection should be considered in
all cases of mucositis, especially in patients having preceding respiratory tract infections (tracheobronchitis).

1. Introduction Mycobacterium tuberculosis [2]. Mycoplasma pneumoniae is

a common cause of community-acquired pneumonia in all
Stevens–Johnson syndrome (SJS) is an immune-mediated age groups. This pleomorphic bacterium lacks cell wall and
disease characterized by a prodromal illness followed by attaches directly to respiratory epithelium, causing damage.
severe mucocutaneous symptoms [1]. SJS and its more se- Extrapulmonary manifestation in skin and mucosa due to
vere form, toxic epidermal necrolysis (TEN), are the result of this bacterium occurs in 25% of cases [3].
an inflammatory response that results in keratinocyte ne- Infectious origin of SJS is suspected if infectious
crosis and perivascular lymphocyte infiltration. Stevens– symptoms precede the onset of skin or mucosal lesion and
Johnson syndrome-toxic epidermal necrolysis (SJS–TEN) serological diagnosis for suspected organism is positive [4].
overlap has the characteristics of both SJS and TEN with the Constitutional symptoms appear at an early stage followed
involvement of 10%–30% of the body surface area, epi- by mucocutaneous involvement. Mucosal lesion is more
dermal detachment, fever, and malaise [1, 2]. SJS was common than cutaneous lesion and is more commonly seen
classically related to a medication hypersensitivity reaction; in oral, genital, and ocular mucosal surfaces [2]. Mycoplasma
however, infectious etiologies are increasingly recognized as pneumoniae-associated mucositis occurs through direct
inciting agents. The common pathogens are Mycoplasma cytotoxic damage and through cross reacting auto antibody
pneumoniae, Enterovirus, hepatitis B virus, Yersinia enter- formation [5]. The histopathological diagnosis of SJS is
ocolitica, Epstein–Barr virus, group A streptococcus, and demonstration of epidermal necrosis [6].
2 Case Reports in Infectious Diseases

The purpose of reporting this case report is to increase

awareness among clinicians about Mycoplasma pneumo-
niae-SJS relationship. To the best of our knowledge, this is
the first case of Mycoplasma pneumoniae-associated SJS-
TEN overlap reported from Nepal.

2. Case Presentation
A 17-year-old young female from Kathmandu, Nepal,
presented to the emergency department of the Institute of
Medicine (IOM) with a generalized painful skin rash along
with extensive blistering with mucosal involvement for one
day (Figures 1–3). She had history of cough, sore throat, and
fever few days prior to the appearance of rash for which she
had taken azithromycin orally. On the 3rd day of oral
medication, she developed rash which was nonpruritic and
painless. There was eruption of bumps starting from the Figure 1: Skin rash over face and neck along with extensive
trunk and spreading all over the body. Her eyelids and lip blistering lesions with mucosal involvement.
were swollen, and this was later associated with blistering
and crusting. Around 20% skin detachment of body surface
area was involved. The patient was clinically diagnosed as
Stevens–Johnson syndrome-toxic epidermal necrolysis (SJS-
TEN) overlap with tracheobronchitis. To find out the cause
of SJS-TEN overlap, azithromycin was stopped. After 2 days
of stopping azithromycin, her clinical symptoms did not
improve, rather new lesions were seen. Then, the bedside
cold agglutination test was done by cooling the blood taken
in EDTA vial at 4°C. Before cooling, the blood formed
smooth coating of the tube. After incubation at 4°C for
3 minutes, macroscopic hemagglutination was observed as
cell clumping in thin film of blood that clinged to the tube
(Figure 4). The clumping disappeared when the tube was
warmed at 35.8°C and reappeared at 4°C (Figure 5). So,
infective cause of SJS-TEN overlap was suspected, the most
common cause being Mycoplasma pneumoniae. Blood was
sent for the investigation of mycoplasma IgM and IgG
antibodies. Also, serial dilutions of the patient’s serum were
mixed with an equal volume of 0.2% washed human O group
erythrocytes, and clumping was observed till titer of 1 : 128
dilution after leaving at 4°C overnight (Figure 6). The
clumping is dissociated at 37°C (Figure 7).
The complete blood count revealed total leukocyte count Figure 2: Skin rash over the back of trunk.
of 8000/μl with lymphocytes of 60% with elevated ESR
(70 mm/hour). Her liver enzymes and serum creatinine were
normal. Test for syphilis (RPR and TPHA), human im-
munodeficiency virus (HIV), hepatitis B and C viruses,
herpes simplex virus, Epstein–Barr virus, influenza A/B, and
Chlamydia pneumoniae were negative.
She was restarted with drug azithromycin and added
hydrocortisone, paracetamol, betadine gargle, mupirocin,
and ciprofloxacin ointment. Punch biopsy of her skin
demonstrated subepidermal inflammation with necrotizing
infundibular epithelium and necrotic keratinocytes consis-
tent with SJS. Mycoplasma IgM antibody report was positive
(2550 U/ml), which suggested the current infection and
confirmed our diagnosis. The same treatment was continued
and her clinical symptoms improved (Figure 8). Figure 3: Skin rash with bullae formation.
Case Reports in Infectious Diseases 3

Figure 4: Clumping of red blood cell along the surface of the tube
at 4°C.

Figure 7: Disappearance of clumping while heating the slide at

37°C.

Figure 8: Patient improving on azithromycin and supportive

treatment.

3. Discussion
Figure 5: Disappearance of clumping while heating the tube at
SJS is a rare, emergency disorder of skin and mucous
36°C.
membranes that occurs secondary to use of certain drugs.
The most common drugs causing SJS are anticonvulsants,
sulfonamides, and oxicam nonsteroidal anti-inflammatory
drugs [7]. SJS is classified as secondary to drugs when the
patient has history of intake of offending drug within eight
weeks before the onset of symptoms. SJS is classified as
infectious if constitutional symptoms appear one week
before the rash and the patient has positive serology [4].
Fever and viral prodrome-like symptoms are seen at an early
stage, followed by skin and mucosal involvement. Mucosal
lesion is more common and is seen in areas like oral, genital,
and ocular region [2].
In the index case, initial presentation was fever, re-
spiratory symptoms, and the involvement of oral mucosa.
These features appeared after intake of antibiotic azi-
thromycin. The first differential diagnosis was SJS-TEN
secondary to the use of antibiotic. Cases of SJS/TEN sec-
Figure 6: Clumping of red blood cell at 4°C in slide. ondary to the use of azithromycin have been reported earlier
4 Case Reports in Infectious Diseases

[8, 9]. SJS is thought to fall within a spectrum of diseases that 4. Conclusion
affect the skin and mucous membranes, including erythema
multiforme minor, erythema multiforme major (or SJS), and Mycoplasma pneumonia infection can cause SJS-TEN
toxic epidermal necrolysis [6, 10]. Mycoplasma pneumonia overlap with both skin and mucosal involvement. Besides
can be associated with isolated mucous membrane disease or considering the offending drugs, Mycoplasma pneumoniae
in combination with skin involvement [11]. Many authors infection should be considered in differential diagnosis of
believe that M. pneumoniae-associated mucositis with the mucocutaneous lesion.
minimal or absence of skin lesions is a separate entity from
SJS, labelled as atypical SJS or M. pneumoniae-induced rash Consent
and mucositis [3, 12]. But in our case, both mucosal and skin
involvement was seen. The term SJS is reserved for cases with Written consent has been provided by the patient for the
<10% skin detachment of the body surface and TEN for publication of this case report and any accompanying image.
those with >30%. Those with detachment of 10%–30% are
termed as SJS-TEN overlap [1, 13]. More than 20% of skin Conflicts of Interest
detachment was seen in our case, so the diagnosis of SJS-
TEN overlap was done. The authors declare that they have no conflicts of interest.
Infectious cause of SJS-TEN overlap in our case was
suspected when clumping occurred in cold agglutination test. Acknowledgments
Cold agglutination test has been used for bedside diagnosis of
mycoplasma infection for very long time [14]. Furthermore, We would like to thank Prof. Jeevan Bahadur Sherchand,
the increasing clinical severity after stopping azithromycin Prof. Bharat Mani Pokharel, Prof. Basista Rijal, Prof. Keshab
pointed to the infectious etiology of SJS-TEN overlap. Di- Parajuli, Asst. Prof. Niranjan Prasad Shah, Hari Prasad
agnosis of Mycoplasma pneumoniae infection is challenging Kattel, Asst. Prof. Dr. Sangita Sharma, Dr. Mahesh Adhikari,
due to the fastidious nature of the organism. Mycoplasmas are Dr. Neha Shrestha, and ICU team of TUTH for their
ubiquitous and are the smallest, free-living microorganisms. constant support and guidance.
After an incubation period of 1 to 4 weeks, the infection
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