|ONLINE ONLY ARTICLES - CASE REPORT
|Year : 2022 | Volume
| Issue : 2 | Page : 150
Toxic epidermal necrolysis due to dual infection of Mycoplasma pneumoniae and Streptococcus complicated by herpes simplex virus
Suma D Gudi, Sambasiviah Chidambara Murthy, Niveditha Nagaraja, Vandana Devendra
Department of Dermatology, Venereology, Vijayanagar Institute of Medical Sciences, Ballari, Karnataka, India
|Date of Submission||10-Dec-2020|
|Date of Decision||24-Jan-2021|
|Date of Acceptance||28-Jan-2021|
|Date of Web Publication||26-Aug-2022|
Sambasiviah Chidambara Murthy
Department of Dermatology, Venereology, Vijayanagar Institute of Medical Sciences, Ballari - 583 104, Karnataka
Source of Support: None, Conflict of Interest: None
Stevens–Johnson syndrome and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, characterized by blistering and epidermal sloughing. They are mainly caused by drugs and less commonly due to infections. A 9-year-old boy presented with fever, cough, atypical target lesions involving >30% of body surface area along with few erosions and positive pseudo-Nikolsky sign. Multiple mucous membranes were involved. Clinical features were consistent with TEN. Radiological and laboratory investigations showed evidence of Mycoplasma pneumonia and Group A Streptococcal infection. The course was further complicated by herpes simplex 1 infection. He responded well to systemic antibiotics, corticosteroids, cyclosporine, acyclovir, and supportive care. This report highlights the occurrence of TEN due to dual infections that further got complicated by a third infection.
Keywords: Erythema multiforme, Mycoplasma pneumoniae, Stevens–Johnson syndrome, streptococcal infections, toxic epidermal necrolysis
|How to cite this article:|
Gudi SD, Murthy SC, Nagaraja N, Devendra V. Toxic epidermal necrolysis due to dual infection of Mycoplasma pneumoniae and Streptococcus complicated by herpes simplex virus. Clin Dermatol Rev 2022;6:150
|How to cite this URL:|
Gudi SD, Murthy SC, Nagaraja N, Devendra V. Toxic epidermal necrolysis due to dual infection of Mycoplasma pneumoniae and Streptococcus complicated by herpes simplex virus. Clin Dermatol Rev [serial online] 2022 [cited 2022 Sep 26];6:150. Available from: https://www.cdriadvlkn.org/text.asp?2022/6/2/150/354741
| Introduction|| |
Erythema multiforme (EM) is a reactive mucocutaneous disorder, which includes a clinical spectrum ranging from EM minor to Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), characterized by extensive epidermal and mucosal detachment., They differ by the extent of the epidermal detachment. SJS involves <10%, SJS-TEN overlap, 10%–30%, and TEN >30% of body surface area. The incidence of TEN is reported to be 1–2 cases per million. Mortality is higher towards the TEN spectrum. We report a rare case of TEN due to dual infection of Mycoplasma pneumoniae and Group A Streptococcus that was further complicated by herpes simplex virus infection.
| Case Report|| |
A 9-year-old male child presented with low-grade fever, dry cough, and target lesions over the trunk for 3 days, which progressed to involve face and extremities in a day. Oral, genital, ocular, nasal mucous membranes were simultaneously affected. His condition further deteriorated over 2–3 days with high-grade continuous fever, productive cough, and breathing difficulty. There was no history of joint pain, drug intake before onset or similar complaints in the past.
General physical examination was normal except for bilateral deep cervical lymphadenopathy. Cutaneous examination showed multiple, bilateral, asymmetrical, typical, and atypical target lesions involving >30% of body surface area, distributed over trunk [Figure 1], face, and extremities including palms. Erythema and skin tenderness was present over the trunk with a positive pseudo-Nikolsky sign, which later progressed to erosions [Figure 2]. Multiple erosions with crusting were present over glans, nasal mucosa, buccal mucosa along with thick hemorrhagic crusts over lips. Bilateral conjunctival congestion was present. Crepitation and rhonchi were present throughout the lung fields and other systems were normal. After 5 days, few grouped vesicles and polycyclic erosions were noted on the lips [Figure 3] and buccal mucosa suggestive of herpes simplex 1 infection.
Blood investigations including complete blood count, renal, liver function tests, and sugar levels were normal. Chest X-ray posteroanterior view [Figure 4], showed reticular opacities suggestive of atypical pneumonia infection. Serology for hepatitis B, C, and human immunodeficiency viruses was negative. Significant serological findings are summarized in [Table 1].
The patient was initially put on injectable azithromycin 250 mg twice daily for 5 days and piperacillin-tazobactam 1.5 g 3 times daily for 7 days along with symptomatic care and nursing. As fever subsided in 2 days, he was started on injectable dexamethasone (0.5 mg/kg) for 5 days with oral cyclosporine (3 mg/kg) for 7 days. He was also started on oral acyclovir, 200 mg 3 times a day for 8 days, on the development of herpes simplex infection. The patient recovered completely, with the healing of mucosal and cutaneous lesions leaving behind post-inflammatory hypopigmentation [Figure 5], in 10 days. The patient is on regular follow-up, with no further recurrences.
| Discussion|| |
In 1922, Stevens and Johnson reported two children who had a fever, conjunctivitis, stomatitis, and generalized exanthema with skin lesions that were distinct from erythema multiforme. In 1956, Lyell reported series of patients with life-threatening, rapidly evolving mucocutaneous reaction, currently known as TEN. The chief causes of TEN are thought to be adverse drug reactions and less commonly, infections. In children, common culprit medications are sulfa antibiotics, phenobarbital, lamotrigine, carbamazepine. M. pneumoniae, Cytomegalovirus, herpes virus, or hepatitis virus infections might also precipitate. Rarely, TEN, presumably induced by streptococcal infection, has been reported. Other predisposing conditions include HIV infection, malignancy, systemic lupus erythematous, radiotherapy, collagen vascular diseases, ultraviolet light, genetics, and underlying immunologic disease.
Dual precipitating factors resulting in SJS/TEN include drug reactions due to nevirapine, co-trimoxazole, etc., in the presence of human immunodeficiency virus infection. Other similar scenario includes allopurinol-induced SJS, in the presence of high levels of human herpes virus-6 infection. Other situations with increased risk of SJS/TEN due to drugs/infections include the presence of cancer, weakened immune system, personal or family history of SJS/TEN. Dual infections resulting in SJS/TEN, are very rare. A case of co-trimoxazole induced SJS/TEN, within a week of recovery, had recurrence due to the presence of dual infections, cytomegalovirus, and Epstein-Barr virus. Our case had evidence of two precipitating factors, i.e., Mycoplasma and streptococcal infection, which is unusual. Individually, M. pneumoniae has been recently recognized to cause M. pneumoniae-induced rash and mucositis (MIRM). MIRM is typically characterized by marked mucositis involving oral, ocular and urogenital regions, with minimal cutaneous involvement. Streptococcus alone precipitating TEN is uncommon. Hence, it may be possible that dual infections may have triggered TEN in our case.
Although the precise mechanism of TEN is still unknown, it is considered as T-cell-mediated, type IV hypersensitivity disorder. The mechanism of apoptosis leading to TEN can be explained by intrinsic and extrinsic pathways. In the intrinsic pathway, electrophilic toxic metabolites produced by keratinocytes damage the mitochondria and produce reactive oxygen species, leading to the production of tumor necrosis factor-α that further damages the cells. The extrinsic pathway includes Fas-Fas ligand interactions, cytotoxic granules as perforin-granzyme and granulolysin, tumor necrosis factor α, micro RNA 18a-5p with cytotoxic lymphocytes and monocyte/macrophages. Annexin induces cell death through necroptosis and is also a part of the extrinsic pathway. Some kinds of virus-specific (memory) T-cells may cross-react to self-tissue, which may be further modified by a culprit drug (heterologous immunity model). Therefore, infection is an important nongenetic factor in the pathogenesis of SJS/TEN.
Incidence of SJS and TEN in the general population are reported to be 1–7 cases and 1–2 cases per million, respectively. Dermatologic manifestations of SJS and TEN may initially appear similar to EM, but lesions of EM are peripherally located target lesions, with <10% body surface area involvement with absent or limited mucous membrane involvement. In SJS and TEN, widespread small blisters develop on a purple macule or on flat atypical target lesions that predominantly occur on the torso than extremities. Pseudo Nikolsky sign is positive involving <10% of BSA in SJS, 10%–30% in SJS-TEN overlap and ≥30% in TEN. Multiple mucosal membranes are usually involved with more predilection toward the oral cavity that heals characteristically with scarring. It has been suggested that SJS/TEN associated with infections are more prone for severe dermatological and ophthalmological involvement, with earlier onset of SJS/TEN, than otherwise. Our case was further complicated by infection with herpes simplex virus 1 infection, which was confirmed serologically.
The recovery time may vary individually, however it usually occurs in 2–3 weeks. Sometimes, long-term complications involving the skin, ocular and oral mucosae, gastrointestinal, genitourinary, pulmonary, and autoimmune diseases can affect the quality of life. Recurrent episodes due to different infections, seem to be slightly higher in the pediatric population. Mortality for SJS-TEN in adults is 34%, whereas it is about 0%–3.6% and 0%–7% in pediatric SJS and TEN, respectively.
Early intervention has a significant role in reducing morbidity and mortality. Withdrawal of offending drugs immediately or treating the cause has a better prognosis. Aggressive supportive care is the mainstay of treatment. Prophylactic antibiotic coverage prevents sepsis which is the most common cause of mortality in TEN. Treatment of both the infectious trigger and reactive inflammatory response should be more effective than either treatment alone. Antibiotic therapy should be based on the knowledge of the pathogen involved. In addition, although definitive evidence regarding potential curative therapies are lacking, corticosteroids and intravenous immunoglobulin use have shown promising results. Cyclosporine, a calcineurin inhibitor, that inhibits cytotoxic T-cells has shown survival benefits when administered during the active phase of SJS/TEN.
| Conclusion|| |
Our case highlights the occurrence of more than one precipitating factor for SJS/TEN, further complicated by another infection. Awareness, early recognition of these factors with suitable intervention, and multidisciplinary approach improves the prognosis in these cases.
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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]