Erythema multiforme; a disease of the oral cavity.pptx A

Target lesions
Bull's eye lesions
Oral Ulcerations
Hyperpigmentation

1. ERYTHEMA MULTIFORME by DR UDEH

2. OUTLINE Introduction Aetiology pathogenesis Classification Clinical manifestation Diagnosis Treatment Approaches Treatment and prognosis Stevens- Johnson syndrome Conclusion

3. INTRODUCTION •Erythema multiforme (EM) is an acute, self-limited, inflammatory mucocutaneous disease that manifests on the skin and often oral mucosa, although other mucosal surfaces, such as the genitalia, may also be involved. •EM is considered a rare condition, with an estimated annual incidence of less than 1%. •EM can occur at any age, but it is most common in young adults, typically between 20 and 40 years old . About 20% of cases occur in children.

4. EM is slightly more common in men than women, with a male-to-female ratio of about 1.5:1 . Infections are the most common triggers for EM, accounting for up to 90% of cases with Herpes simplex virus (HS) the most frequent culprit, especially for EM minor. • Mycoplasma pneumonia, particularly in children. • Recurrences of EM are common, especially in individuals with HSV-associated EM.

5. AETIOLOGY The etiology of erythema multiforme is multifactorial including ; 1.Infections *Viral eg HSV,Adenovirus,EBV,VZV,HepatitisA,B,C,Mumps,enterovirus,cytomegalovirus,measles, *bacterial eg mycoplasm pneumonia,borreliosis, catscratch disease, diphtheria, salmonellosis,TB * fungal 2.Food allergy eg Benzoic acid(a preservative) 3. autoimmune conditions eg Systemic Lupus Erythematosus leading 4.Malignanc y

6. 4.Malignancy eg lymphoma 5. immunizations eg BCG vaccine,Oral Polio,Diphtheria/tetanus vaccine 6. radiation exposure 7.Contact with heavy metals,herbal agents,topical therapies,poison ivy 8.HIV and HIV treatment medications 9.Antibiotics eg Penicillin,Cephalosporins,macrolides,sulphonamides 10.Antituberculosis agent 11.NSAIDS 12.Anticonvulsants

7. PATHOGENESIS The exact pathophysiology behind erythema multiforme is unknown. Most data has been collected to study the underlying pathogenesis behind HSV-associated erythema multiforme. The mechanism by which HSV causes erythema multiforme is thought to involve a cell-mediated immune response against viral antigens in skin lesions. Viral DNA in biopsy specimens of individuals with affected skin supports this theory.

8. In the development of mucocutaneous lesions of HSV-associated erythema multiforme, an interplay between CD34+ Langerhans cell precursors, viral DNA fragments, epidermal keratinocytes, HSV-specific CD4 TwI cells, interferon (IFN)-Y, and autoreactive T cells is observed. These interactions lead to epidermal damage and the characteristic inflammatory infiltration of cutaneous lesions of erythema multiforme. Damage to the epithelial cells is caused by cell-mediated immunity. During the early phase of the disease, an influx of macrophages and CD8 T lymphocytes occurs, which release a wide range of cytokines that mediate the inflammation and resultant cell death.

9. .In drug-induced erythema multiforme the re is presence of tumor necrosis factor (TNF)-alpha instead of IFN-gamma, making the earliest pathological feature the necrosis of keratinocytes. . Genetic susceptibility also plays a role in the development of erythema multiforme. Recurrent erythema multiforme has been found to have an association with human leukocyte antigen (HLA) types A33, B35, DR4, DQB1*03:01, DQ3, and DR53.[24]

10. CLASSIFICATION Can be classified; (a) based on the degree of mucosal involvement (b) based on the nature and distribution of the skin lesions. EM Minor EM Major

11. EM MINOR Acute, self-limited, occasionally recurrent. Duration: 1-3 weeks characterised by target lesions , which are usually symmetrically distributed on the extensor surfaces of the arms and legs. In volvement of the mucous membrane is limited to one site only - usually the oral mucosa. mild extension of erythematous patches or superficial erosions of the oral mucosa and the lip.

12. EM MAJOR Acute, self limited, episodic, duration: 1-6 weeks is more severe, and is characterised by involvement of multiple mucous membranes -the oral cavity, and others including the genital, ocular, laryngeal, or esophageal mucosae, or a combination. The skin lesions usually resemble those of EM minor but may also be atypical, raised and can include bullae.

13. CLINICAL MANIFESTATION •EM generally affects those between ages 20 and 40 years • 20% occurrence in children • Patients with recurrent EM have an average of six episodes a year . • Episodes usually last several weeks before remission. •There may be a prodrome of fever, malaise, headache, sore throat, rhinorrhea,cough

14. • These symptoms suggest a viral (especially respiratory tract infection, and this is not surprising since infectious agents are known to trigger EM. • Skin lesions appear rapidly over a few days and begin as red macules that become papular, starting primarily in the hands and moving centripetally toward the trunk in a symmetric distribution. • The most common sites of involvement are the upper extremities, face, and neck. • Genital and ocular sites are other sites that can be affected by EM. The classic skin lesion consists of a central blister or necrosis with concentric rings of variable color around it called typical "target" or "iris" lesion that is pathognomonic of EM.

15. •The skin may feel itchy and burnt. •Post inflammatory hyperpigmentation is common in dark-skinned individuals and may be worsened by sun exposure. INTRA ORALLY; •Range from mild erythema and erosion to large painful ulcerations, irregular bullae, erosions or ulcers surrounded by extensive erythema. • ulcers may be large and confluent, causing difficulty in eating, drinking, and swallowing, and patients with severe EM may drool blood-tinged saliva. .Extensive lip involvement with inflammation, ulceration, and crusting is common.

16. • The most commonly affected sites are the lips (36%), buccal mucosa (31%), tongue (22%), and labial mucosa (19%).

17. DIAGNOSIS The diagnosis of erythema multiforme is based on history and clinical examination. Certain investigations, including skin biopsy, may help establish the diagnosis in cases with clinical diagnostic uncertainty. A skin biopsy of the lesion center can be performed for histological study with immunofluorescence, as it shows epithelial intercellular edema with keratinocyte necrosis, which is responsible for an intrepidermal or subepidermal blister covered with a necrotic epidermis.

18. Others may include; Full blood count: May show moderate leukocytosis, eosinophilia, neutropenia, mild anemia, and thrombocytopenia E SR : May be elevated in severe cases Immunofluorescence study: Can detect specific HSV antigens within keratinocytes PCR : Can detect HSV DNA primarily within the keratinocytes Chest x-ray: May show interstitial radiological infiltrate (mainly in erythema multiforme due to Mycoplasma pneumonia)

19. DIFFERENTIAL DIAGNOSIS includes Urticaria (hives) Drug eruptions Stevens-Johnson syndrome Vasculitis Herpes simplex virus infection Viral exanthem Lupus erythematosus Bullous pemphigoid

20. TREATMENT APPROACHES The treatment approaches of erythema multiforme can be divided into ; Str ategies for acute episodes Su ppressing recurrent disease Supportive measures is ai med at reduc ing the patient's burden of symptoms until the natural resolution occurs, usually in 2 weeks in acute. In recurrent cases, the focus is on managing acute symptoms and eliminating the triggering factor to prevent future episodes.

21. TREATMENT Acute phase treatment: The first step in managing erythema multiforme is to remove the underlying cause, eg. discontinuing the medication that could have triggered the reaction. Mycoplasma pneumonia infection should be treated with antibiotics without waiting for the results of the bacteriological examinations, especially if a cough or radiological evidence is present. Treat herpes with acyclovir or valacyclovir if it is suspected.

22. Topical treatment includes ; Antiseptic mouth washes to keep the ulcers clean Topical corticosteriod and antihistamine for itching A nesthetic agents for pain relief. Vaseline for the lips Ophthalmologists involvement in ocular comp lications Hospitalization may be required for severe pain, dehydration, or difficulty eating. While systemic corticosteroids and intravenous immunoglobulins can be explored .

23. Prevention of Recurrence ; Herpes is the most common cause of recurrent erythema multiforme. Typical regimens would include acyclovir 400 mg twice daily, valacyclovir 500 mg twice daily, for at least 6 months. Preventive therapy is indicated for patients with more than 5 erythema multiforme outbreaks per year or fewer in the case of severe forms If no cause is identified, other therapeutics may be used in the long term, eg, hydroxychloroquine, dapsone, or early treatment with systemic corticosteroids. In nonresponsive cases, immunomodulation may be required with medications including mycophenolate mofetil, dapsone, or azathioprine.

24. PROGNOSIS EMM: excellent prognosis, with resolution within a few weeks. Recurrences are common, especially with HSV. EMJ: Prognosis is more variable, depending on the severity and presence of complicationsThe mortality rate in erythema multiforme major is less than 5% and is directly proportional to the extent of sloughed epithelium. The mucosal lesions always take longer to heal. The healing of the mucocutaneous lesions is without scarring but with frequent dyschromia. Recurrences are seen in less than 5% of cases, mainly in forms due to herpes infection .

25. The main long-term risk is the development of synechias or adhesions in case of mucosal involvement. Ocular sequelae can be severe, leading to blindness. Poor prognostic factors include renal dysfunction, prior bone marrow transplant, visceral involvement, immunosuppression, and advanced age. Rarely, some patients may develop recurrent or persistent forms, which are recalcitrant to treatment. This may occur in patients with HSV infection, reactivation of Epstein-Barr virus, inflammatorybowel disease, and occult renal cell cancer.

26. STEVENS-JOHNSON SYNDROME/TEN S tevens-Johnson svndrome/toxic epidermal necrolvsis is a rare. acute, serious, and potentiallY fatal skin reaction in w hich there are sheet-like skin and mucosal loss accompanied by system ic symptoms. SJS / TEN is classified by the extent of the detached skin sur f ace area S JS : less than 10% body sur fa ce area. Overlap SJS/TEN 10% to 30% body surface area TEN more than 30% body surface are a Go

27. SJS is a less severe variant of T EN and separate clinically and aetiopathogenetically from EM. They are more severe and tend to arise on the chest rather than the extremities on erythematous and purpuric macules; these lesions are called "atypical targets." • SJS is much more likely to be associated with medication use and Mycoplasma pneumonia infection (especially in children ) and rarely with HSV infection, whereas EM is much more likely to be associated with HSV infection.

28. AETIOLOGY OF SJS The drugs that most commonly cause Stevens-Johnson syndrome/toxic epidermal ; Anticonvulsants: lamotrigine, carbamazepine, phen yt oin, phenobarbitone Allopurinol, especially in doses of more than 100 mg per day sulfonamides. cotrimoxazole, sul f asalazine Antibiotics: pencillins , cephalosporins ,q uinolones. minoc y cline Nevirapine (non-nucleoside reverse-transcriptase inhibitor)

29. Nonsteroidal anti-inflammatory drugs (NSAIDs) (oxicam type mainly) Paracetamol Contrast media Genetic factors include human leukoc y te antigen (H L A) allot yp es that lead to an increased risk of Stevens-Johnson syndrome/toxic epidermal necrolysis when exposed to aromatic anticonvulsants and allopurinol.

30. CLINICAL FEATURES The illness begins with nonspecific symptoms such as fever and malaise,upper respiratory tract symptoms such as a cough, rhinitis, sore eves. Over the next three to four days, a blistering rash and erosions appear on the face,trunk,limbs and mucosal surfaces Erythematous, targetoid, annular, or purpuric macules,flaccid bullae,large painful erosion Mucosal ulceration and erosions can involve lips. mouth, pharynx,esophagus and GI tract,eyes, genitals. The patient is very ill, anxious, and in pain. Liver, kidneys, lungs, bone marrow, and joints may be affected.

31. Investi gations may include ; Urgent frozen sections of skin biopsy: full-thickness skin necrosis Direct immune mluorescence: negative FBC : anemia , neutropenia ,atypical lymphocytosis Liver function test : elevated transaminases , hypoalbuminemia Renal functio n:Reduced GFR,increased creatinine and urea Pul monary fu nction: bronchial mucosal sloug h ing on bronchoscopy, interstial infiltrates on Chest Xray Cardiac function: abnormal ECG and imaging.

32. The severitv of Stevens-Johnson s yn drome/toxic epidermal necrolvsis is assessed usingSCORTEN. One point is scored for each of the following seven criteria at admission : Age older than 40 year Presence of a malignancy Heart rate of more than 120 bpm Initial percentage of epidermal detachment greater than 10% Serum urea level greater than 10 mmoll Serum glucose level greater than 14 mmoll S erum bicarbonate level less than 20 mmol.

33. A SCORTEN ranges with their associated mortalit y (in %) are as follows: score 0-1 (3.2%). score 2 (12.1%). score 3 (35.3%). score 4(58.3%) score 5 (>90%) Management is multidisplinary

34. CONCLUSION Erythema multiforme is a mucocutanes lesion mostly triggered by HSV,Infections,Drugs characterised by target lesions on the skin.Mucosal involvement including mouth,eyes,genitalia. Diagnosed primarily clinically and Managed by treating underlying cause and supportive care to relieve symptoms. with SJS different and more severe than EM.

35. REFERENCES Wissem Hafsi; Talel Badri. (2024)Erythema Multiforme StatPearls [Internet]. Retrieved fromhttps://www.ncbi.nlm.nih.gov/books/NBK537024/ Amanda M. Oakley; Karthik Krishnamurthy,(2023)Stevens-Johnson Syndrome. StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK5476721 Dr Uwaila Otakhoigbogie, (2024)Erythema Multiforme Dr Adekanmbi,Note on Erythema Multiforme