I. Etiology and mechanism
1. Pathogenesis
Direct immunofluorescence reveals linear deposits of C3 and IgG in the basement membrane of the skin around the lesions, and indirect immunofluorescence reveals that 70% to 85% of patients with pemphigus vulgaris have circulating antibodies to IgG in the anti-epidermal basement membrane band, and a significant number of patients also have antibodies to IgE in the basement membrane band. The presence of a large number of eosinophils and degranulation around the damage makes it possible that type I metaplasia is involved in lesion formation.
2. Pathogenesis
In addition to complement C3, other components of the classical and alternative complement activation pathways and complement regulatory protein β1H are also deposited in the basement membrane zone of patients with herpetiform aspergillosis. These studies demonstrate that herpetic IgG activates complement in the classical pathway and the alternative complement pathway in the C3 amplification mechanism.
II. Clinical manifestations
1. Typical rash.
The basic damage is a tense, thick-walled blister that occurs on the basis of normal skin or erythema, with round or oval-shaped blisters, mostly about 1 cm in diameter, but also up to several centimeters like a pigeon’s egg. The wall of the blister is thick and does not break easily, and the blister does not expand to the surrounding area when squeezed (negative for Ney’s sign). The contents of the blisters are mostly clear, with a few being bloody. The blisters become vesicles with crusts, which are easily healed, and the blister fluid is purulent when secondary infection occurs.
2. Prevalent sites and other accompanying symptoms.
The lesions are usually found on the trunk and the flexors of the extremities, and the early lesions can only show puffy erythema without blisters, which can be misdiagnosed as erythema multiforme or drug rash. About half of the patients have damage to the oral mucosa, manifesting as blisters or vesicles on the oral maxillary mucosa and buccal mucosa. However, the oral lesions are much less severe than those of aspergillosis. Patients often feel itchy.
The general health condition is usually not affected in the early stages of the disease.
It is more common in the elderly. The course of the disease is chronic and the prognosis is good. As long as the treatment is timely and proper medication is used, it can be cured.
Pathological examination
Histopathological examination of the newly emerged blisters showed subepidermal blisters with lymphocytes and varying numbers of eosinophils infiltrating within the blisters and in the dermis below the blisters.
Immunopathology: direct immunofluorescence examination shows a continuous linear fluorescent band in the basement membrane area, mainly IgG deposition. Anti-basement membrane antibodies can also be measured by indirect immunofluorescence. 70%-80% of patients have high antibody potency in the serum, which is meaningful for diagnosis.
IV. Diagnosis
Diagnostic points: skin damage is characterized by tension blisters with blisters that do not break easily, while the oral cavity is less frequently involved, and the skin is negative for mucosal blisters. Histopathological examination shows fissures or blisters between epithelium and connective tissue, mostly subepithelial blisters, without spicule loosening, and connective tissue with a large number of eosinophils, neutrophils and lymphocytes infiltration. Direct immunofluorescence examination reveals a continuous linear fluorescent band in the basement membrane area, which is mainly a deposit of IgG. Indirect immunofluorescence can also measure anti-basement membrane antibodies. 70%-80% of patients have high antibody potency in the serum, which is meaningful for diagnosis.
V. Treatment
The principle is early diagnosis and early treatment. The more timely the treatment, the faster the skin lesion control and the better the prognosis.
The first choice is glucocorticoids, often using prednisone, the dosage depends on the extent of the lesions and the severity of the lesions. For mild cases with lesions covering less than 10% of the body surface, the initial dose is usually 30mg/day, for moderate cases with lesions covering 30% of the body surface, it is 40–50MG(mg/day), for severe cases with lesions exceeding 50% of the body surface, it is 60–80MG(mg/day), if the disease cannot be controlled within 3–5 days and there are still new rashes, the dosage should be increased in time. After the lesions are controlled and maintained for one to two weeks, the drug should be gradually reduced to reach a maintenance level. When the dose is reduced to 15-20mg/day, the dose can be gradually changed to every other day. In the process of drug reduction, the disease should be closely observed, once there is a new rash, then the drug should be temporarily reduced. In severe cases, when the disease cannot be controlled with high doses of corticosteroids, immunosuppressants such as methotrexate, cyclophosphamide, cyclosporine, and raglan polysaccharide can be used in combination.
Most patients with herpetiform aspergillosis are old and often have other diseases. When diabetes mellitus and tuberculosis cannot be treated with corticosteroids, oral tetracycline 500mg 4 times a day or memantine 100mg twice a day and nicotinamide 200mg 3 times a day can be used, which is effective in some patients, especially in mild cases.
Supportive therapy is important, and since most patients are old, attention should be paid to strengthening nutrition and maintaining hydropower mediator balance. During the treatment period, attention should be paid to the side effects of corticosteroids and the resulting comorbidities.