Erythema Multiforme: What You Need to Know, Part-2

Erythema Multiforme: What You Need to Know, Part-1

Oral Manifestations

About 70% of Erythema multiforme cases present with characteristic oral features.
The oral lesions have a predilection for the non-keratinized mucosa and anterior parts of the oral cavity. The primary sites involved are:
- the Lips (36%),
- buccal mucosa (31%)
- tongue (22%), and
- labial mucosa (19%).
Erythema multiforme presents with a wide array of oral manifestations, ranging from shallow erythematous and hyperkeratosis plaques to tender, deep-seated hemorrhagic bullous and erosive lesions.
The initial oral lesions present edematous and erythematous macular lesions of the lips and buccal mucosa.
Advanced lesions manifest as multiple vesiculobullous lesions that eventually break down and form a pseudomembrane.
Swollen lips, along with typical blood-tinged crusted lesions, are the hallmark of Erythema multiforme.
Intact vesicles are infrequently seen and eventually rupture, forming irregular ulcerative lesions.
Although targetoid lesions may appear on the lip, they are rarely seen intraorally.
The oral mucosa is the most frequently affected mucous membrane. However, as the disease progresses further, it may involve any mucosa, including the tracheobronchial or gastrointestinal tract epithelium.

Erythema multiforme major presents with larger oral lesions as compared to Erythema multiforme minor and ulcerative lesions of multiple mucous membranes may be seen in more than 50% cases.
Constitutional features such as trismus, dysarthria, dysphonia, and/or dysphagia may also be seen.
In most cases, the oral lesions heal without scarring, however, occasionally hyperkeratotic plaques mixed with erythematous areas may also be seen.

Pathophysiology

Erythema multiforme is often associated with viral or bacterial infections, especially HSV.
Studies have demonstrated the presence of HSV-DNA acute or sequellae Erythema multiforme lesions.
The predisposing factors are unknown.
HLA-DQ3 is reported to be associated with postherpetic Erythema multiforme and has been suggested as an additional diagnostic marker. Other human leukocyte antigen groups have also been reported as markers of recurrent Erythema multiforme.
The damage to the epithelial cells is via cell-mediated immunity. During the early phase of the disease, there is an influx of macrophages and CD8 T lymphocytes, which release a wide range of cytokines that mediate the inflammation and resultant cell death.
When the process is due to drug hypersensitivity, the earliest pathological feature is necrosis of keratinocytes.

Histopathology

A punch biopsy can be used to confirm the diagnosis of Erythema multiforme.
The classic lesion will reveal vacuolar interface dermatitis with marked infiltration with lymphocytes along the dermo-epidermal junction.
In addition, one may see dyskeratosis of basal keratinocytes and hydropic changes. With advanced lesions, there is usually epidermal necrosis, subepidermal blisters, and vesiculation.
There is a predominance of CD8 T lymphocytes and macrophages.

Staging

Erythema multiforme minor essentially touches the skin with typical lesions and symmetrical acral disposition. The mucosal involvement is rare, and when it is present, it is light and affects a single mucosa, often the mouth.
In Erythema multiforme major, the skin lesions are more extensive but do not exceed 10% of the body surface area. Typical target lesions are present. The mucosal involvement is severe and affects at least two different mucosal sites; the oral mucosa is typically affected.

Prognosis

The prognosis is mainly related to the body surface area detached. The healing is obtained spontaneously in 2 to 3 weeks for the Erythema multiforme minor and 4 to 6 weeks for the Erythema multiforme major.
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.
The main long-term risk is the development of synechias in case of mucosal involvement. Ocular sequelae can be serious, leading to blindness. At the genital level, synechiae can produce functional sequelae.
Particular vigilance during the acute episode must be implemented to prevent these sequels. The vital prognosis is only exceptionally brought into play when the care is adapted. Two situations that deserve particular vigilance are (1) severe mucosal involvement and (2) bacterial superinfections.
Poor prognostic factors include renal dysfunction, prior bone marrow transplant, visceral involvement, and advanced age.
Unfortunately, some patients may develop continuous Erythema multiforme, which is recalcitrant to treatment. This may occur in patients with HSV infection, reactivation of EBV, inflammatory bowel disease, and occult renal cell can

Complication

While mucosal lesions heal completely, the skin lesions may result in scars. In addition, strictures of the urethra, esophagus, vagina, and anus are not uncommon. Urinary retention, phimosis, and hematocolpos have all been reported as a result of strictures. Eye complications occur in up to 20% of patients and can result in uveitis, conjunctivitis, scarring, panophthalmitis, and permanent blindness. Epiphora can result if the nasolacrimal duct is narrowed. Many patients develop dry eye syndrome and corneal scarring.

Diagnosis

Oral features are quite characteristic with the formation of blisters on the lips and oral mucosa which eventually break and coalesce to form erosive and ulcerative lesions, followed by greyish pseudo membrane. Gingival Desquamation, hemorrhagic crusted lip lesions, and a positive Nikolsky’s sign is also seen.
diagnose erythema multiforme based on characteristics of lesions that include
- Size
- Shape
- Colour
- Distance between each lesion
- Involvement of eyes, mouth or genitals
- Your rovider may need to perform a skin biopsy to diagnose eruthema multiforme.
- Diagnosis is often made based on history and clinical examination.
- Where there is doubt about the diagnosis, consider:
- Complete blood examination
- Liver functions tests
- ESR
- Serological testing for infectious causes
- Chest x-ray.

Skin biopsy with histopathology and direct immunofluorescence can be non-specific but helps to distinguish erythema multiforme from other more serious differentials, such as autoimmune blistering diseases. Upper dermal oedema and individual epidermal keratinocyte necrosis are suggestive pathological features.

All patients with recurrent erythema multiforme should be tested for herpes simplex virus, including sampling of skin or mucosal lesions. In recurrent or persistent erythema multiforme without a clear precipitant, consider work up for solid organ or haematological malignancies

Treatment

Topical treatment is based on antiseptics for bullous lesions, antiseptic mouthwashes, and anaesthetics. Ophthalmologists manage ocular involvement. Healing is promoted by the application of vaseline on the lips and vitamin A ointment in the eyes.
Hospitalisation is needed in case of the inability to eat, pain control, or hydration. The role of systemic corticosteroids and intravenous immunoglobulins has been discussed without demonstrating their effectiveness. Daily monitoring is necessary in cases of extensive lesions.
Etiological treatment must be instituted when a cause (or sometimes probable cause) is identified. Mycoplasma pneumoniae infection justifies treatment with azithromycin for three days without even waiting for the results of the bacteriological examinations, especially if there is a cough or pulmonary radiological abnormalities. Some suggest treating with aciclovir or valaciclovir if herpes is suspected.
Symptomatic management, along with recognition and alteration of the alleged precipitating factors, is usually sufficient in the majority of cases. However, in advanced lesions, steroid therapy may be helpful

Prevention of Recurrent Erythema multiforme Form

Herpes is the most common cause. Even if specimens have not established the evidence, long-term treatment with aciclovir or valaciclovir should be proposed.
It is indicated, in theory, for patients with more than 5 Erythema multiforme outbreaks per year or fewer in the case of EP severe forms. Valaciclovir treatment prevents HSV-induced Erythema multiforme outbreaks but appears to have no impact on an Erythema multiforme outbreak if it starts after the beginning of the eruption.
If no etiology is identified, other therapeutics may be proposed in the long term, such as hydroxychloroquine, dapsone, or early treatment of sprouts by systemic corticosteroids.

Admission

Severe cases of Erythema multiforme will require admission to manage the complications, dehydration, and any infection.
These patients are best managed in an ICU and treated like a patients. However, debridement should be avoided while the lesions are progressing.
The eroded lesions should be bathed in Burrow’s solution or saline with non-adherent dressings.
All offending drugs must be immediately discontinued.
While one may apply silver nitrate, silver sulfadiazine should be avoided because it may worsen the injury. Re-epithelialization can take 7 to 21 days.
Nutrition support is vital, and if the patient has diarrhea, TPN is an option.
Central lines should be avoided to lower the risk of infection, and strict asepsis should be practiced.
Hypothermic patients may require a warming blanket, warmed IV solutions, or a heating lamp. Deep venous thrombosis and stress ulcer prophylaxis is highly recommended.
Diffrential diagnosis
- urticaria
- viral exenthem
- steven Johnson syndrom
- fixed drug eruption
- bullous pemphigoid
- paraneoplastic pemphigus
- polymorphus ligh eruption
- rowell syndrom (erythema multiforme-like lesions in systemic lupus erythematossus)

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