bubble_chart Overview

Erythema multiforme exudativum (EME) is an acute exudative inflammatory condition of the skin and mucous membranes, also known as erythema multiforme (EM). Given the prominent feature of exudation in this disease, it is more accurate to refer to it as erythema multiforme exudativum. This name fully captures the essence of the condition.

bubble_chart Etiology

Since the disease cause of erythema multiforme exudativum has not yet been clarified, there are many disease cause theories.

1. Drug allergic reactions: This mainly refers to individuals with an allergic constitution, who are prone to allergic reactions after using certain drugs, resulting in various forms of erythema, blisters, erosions, etc., on the skin and mucous membranes. Common sensitizing drugs include sulfonamides, antibiotics, barbiturates, phenylbutazone, antipyretics, Dilantin, or carbamazepine.
2. Immune factors: Many scholars have studied the relationship between immunity and erythema multiforme exudativum, suggesting that immune factors may also be a possible cause of the disease. For example, Kraeger et al. (1973) measured the macrophage aggregation activity (MAA) in five patients with erythema multiforme exudativum and found increased MAA in two cases. Safai et al. (1975) reported elevated levels of IgG in both serum and blister fluid in two patients with bullous erythema multiforme exudativum diagnosed clinically and histologically, while early blister fluid showed decreased complement components and increased immune complexes. Kazmicrowski et al. (1978) used direct immunofluorescence to examine skin biopsies from 17 patients with erythema multiforme exudativum and found deposits of C3 and/or IgM on small blood vessels in the papillary layer in all specimens from early lesions within 24 hours of onset.
3. Viral infections: Soltz-Szots (1963) reported that treatment of recurrent herpes simplex with herpes simplex virus vaccine induced erythema multiforme exudativum. Shelley (1967) replicated the occurrence of erythema multiforme exudativum by subcutaneous injection of 0.01 ml of herpes simplex virus vaccine. In addition to herpes simplex virus, Coxsackie virus, measles virus, echovirus, and poliovirus can also act as antigens to trigger the disease. Therefore, erythema multiforme exudativum is widely recognized as an allergic reaction.
4. Bacterial infections: These are mainly suppurative coccal infections, which act as antigens to cause the disease. These include hemolytic streptococci, staphylococci, Brucella, diphtheria bacilli, and erysipeloid bacilli.
5. Mycoplasma infections: Currently, Mycoplasma pneumoniae is considered a pathogenic agent. For example, Lyell et al. (1967) isolated Mycoplasma pneumoniae from the blisters of 2 out of 13 cases of severe erythema multiforme exudativum, with elevated complement-fixing antibody titers. They also isolated Mycoplasma pneumoniae, Mycoplasma orale, and Mycoplasma hominis type I from the oropharynx of five other patients with erythema multiforme exudativum. Regarding the pathogenic role of mycoplasma, it is currently explained in two ways: one is the direct adhesion of mycoplasma membrane and its metabolites to the respiratory tract, and the other is an allergic reaction.
6. Other factors: Such as mental stress, excessive fatigue, food allergies, focal infections, or exposure to cold can also induce the disease.

bubble_chart Pathological Changes

Incomplete keratinization of epithelial cells, intracellular or extracellular edema, inflammatory cells visible in the epithelial layer, mainly monocytes and polymorphonuclear cells; intraepithelial or subepithelial blister formation; the superficial tissue of the epithelium may show severe liquefaction degeneration; due to degeneration of basal cells beneath the blister, intraepithelial blisters can transform into subepithelial blisters; basement membrane thinning or disappearance; inflammatory cell infiltration in the lamina propria, consisting of eosinophils and polymorphonuclear cells; particularly notable are the significant dilation and congestion of small blood vessels, endothelial cell swelling, and red blood cell extravasation.

bubble_chart Clinical Manifestations

The disease is self-limiting; it predominantly affects young adult males; onset is abrupt, often preceded by prodromal symptoms such as headache, dry mouth, sore throat, and fatigue; during episodes, joint pain and elevated body temperature occur. It is generally classified into mild and severe types.

I. Mild Type

The mild type of this disease primarily refers to cases involving the oral mucosa or accompanied by skin lesions, with generally milder systemic symptoms.

1. Oral mucosa: Lesions on the oral mucosa may occur alone or simultaneously or sequentially with skin involvement. Lesions can appear anywhere on the oral mucosa.
   1. Lips: The incidence of multiform exudative erythema in the oral cavity is 70%, with lesions often appearing on the lips, making them a common site for this disease, particularly the lower lip. Initially, localized congestion and edema occur; the erythema on the mucosa is less distinct and well-defined compared to skin erythema. Due to friction from speaking and eating, blisters on the oral mucosa are prone to rupture, making the blister stage rarely observable. Examination often reveals erosions of varying sizes on the inner lip mucosa and vermilion border, with significant exudation and slow spontaneous or provoked bleeding, leading to the gradual thickening of blood crusts. Eventually, a purplish-black, cocoon-like blood crust forms. Movement of the lips during speech or eating can exacerbate bleeding; upon waking, the lips may adhere, with the vermilion border covered by purplish-black crusts, preventing mouth opening.
   2. Intraoral: Intraoral lesions typically occur on the buccal mucosa. Clinical manifestations mainly include congestion, edema, erosion, and exudation, with bleeding less pronounced than on the lips. Due to saliva secretion and its cleansing effect, bleeding may be overlooked, though some patients recall blood traces in their saliva during inquiry.
2. Skin manifestations: The skin manifestations of multiform exudative erythema are prominent. Round or oval erythemas of various forms commonly appear symmetrically on the dorsa of the hands and feet, extensor surfaces of the limbs, or the face. Initially bright red and slightly raised, the erythemas gradually darken. As the lesions progress, they expand centrifugally, forming concentric rings with a bright red outer ring, a less intense inner ring, and a dark red center, resembling a target or "iris" pattern—now termed "targetoid erythema," a hallmark of this disease. The center of these erythemas may also develop blisters, sometimes with hemorrhagic spots or deep, non-raised blisters. Patients experience localized burning and cutaneous pruritus discomfort.

II. Severe Type

The severe type refers to the more serious form of this disease. In 1922, Stevens and Johnson first reported multiform exudative erythema involving the oral mucosa and eyes, a severe variant now known as Stevens-Johnson syndrome. In addition to severe systemic symptoms, multiple organ damage occurs.

1. Systemic condition: Systemic symptoms are pronounced and severe, including elevated body temperature (up to 40°C), headache, sore throat, and even joint pain. Laboratory tests show increased total white blood cell count and lymphocytes, with a sharply elevated erythrocyte sedimentation rate. Patients often present with an acutely ill appearance, flushed face, closed eyes, fatigue, and reluctance to speak, sometimes nearing collapse.
2. Oral mucosa or lips: Localized congestion, edema, and erosions of varying sizes are present, with exudation, bleeding, and increased saliva. The vermilion border may already have blood crusts. Pain interferes with speech and eating.
3. Skin: Typical targetoid erythemas appear, varying in number and size, with adjacent lesions sometimes overlapping or merging.
4. Eyes: Acute inflammation is usually bilateral, with conjunctival congestion, eyelid swelling, medial canthus erosion, excessive discharge, and photophobia. This manifests as conjunctivitis or keratitis, sometimes involving multiple layers of ocular inflammation.
5. Genitalia: The genital and anal mucosa may show congestion, erosion, and pain.
6. Others: It may also be complicated by tracheitis, bronchitis, and pneumonia.

The aforementioned multi-organ manifestations of damage primarily involve congestion, edema, and erosion in the oral cavity, along with target-like erythema on the skin. When combined with lesions in one or two other areas, the diagnosis can be confirmed. This type of multi-organ damage belongs to the category of pluriorificial erosive ectodermal disease, now uniformly referred to as Stevens-Johnson syndrome.

bubble_chart Treatment Measures

1. Analysis of medication history: Analyze and trace recent medication history, dietary history, and exposure history; discontinue suspected allergenic foods and medications. If the medication in use is essential and cannot be discontinued, efforts should be made to replace it. Provide nutritional liquids, soft foods, etc.
2. Systemic medication: Refer to the systemic treatment for drug-induced allergic stomatitis.
3. Local management
   1. Before meals, a 1% procaine solution can be used as a mouth rinse for 3–5 minutes to relieve pain;
   2. Wet compresses: Suitable for cases of lip erosion with significant exudation or when removing blood scabs. Use a 0.02% furacilin wet compress or warm saline solution to reduce inflammation, decrease exudation, or soften scabs for easier removal and medication application;
   3. Application of antibiotic preparations: When exudation from the eroded area decreases, antibiotic membranes can be applied multiple times a day. Before sleep, to prevent adhesion of the upper and lower lips, apply antibiotic ointments such as chlortetracycline or erythromycin ointment.

bubble_chart Differentiation

The mild form of this disease should be differentiated from drug-induced stomatitis and contact stomatitis; the severe form of this disease—Stevens-Johnson syndrome—needs to be distinguished from Behcet syndrome.