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Case 1.

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Female↗

Long-term interferon-alpha therapy induces autoantibodies against epidermis.

BACKGROUND: While interferon (IFN) is known for its immunoregulatory properties, it has also been shown to induce autoimmune disorders such as lupus erythematosus, hypothyroidism, antiphospholipid syndrome and, recently, bullous pemphigus-like eruptions. OBJECTIVE: The purpose of this study was to determine the percentage of antibodies against epidermis induced by IFN-alpha therapy, as detected by indirect immunofluorescence and Western blotting (WB). METHOD: We have studied the sera of 47 patients treated with low doses of IFN-alpha 2a for malignant melanoma or cutaneous T cell lymphoma for a period of 12 months. These sera were tested by standard IIF and WB. RESULTS: 32% of patient sera were positive after 6 months of treatment. Antibodies against epidermis were most often of the pemphigus type as confirmed by WB. Two types of labeling were noted for anti-basement membrane antibodies: basal cytoplasmic pattern in 4 sera and along the dermal side of the basal keratinocytes in 2 sera. CONCLUSION: This study brings biological arguments to confirm the direct role of IFN-alpha in the development of pemphigus-like eruption, and emphasizes the need for clinical follow-up of patients treated with IFN-alpha over a long period of time.

Adult↗

A retrospective analysis of tissue-fixed immunoreactants from skin biopsies maintained in Michel's medium.

656 skin biopsies with positive direct immunofluorescence from the UK and overseas were studied over a 2-year period. The length of time biopsies had remained in Michel's medium at pH 7.0 in various diseases (pemphigoid, pemphigus, linear IgA disease, epidermolysis bullosa acquisita, lupus erythematosus, vasculitis, amyloid, lichen planus and dermatitis herpetiformis) was analysed. We concluded that direct immunofluorescence remained positive at 6 months and that Michel's medium is a reliable long-term maintenance medium for skin biopsies.

Autoimmune Diseases↗

Efficacy and safety of intravenous immunoglobulin for immune-mediated skin disease: current view.

Intravenous immunoglobulins (IVIgs) exert a variety of immunomodulating activities and are, therefore, increasingly being used for the treatment of immune-mediated as well as autoimmune diseases. There is also accumulating evidence that high-dose IVIg (hdIVIg) is highly efficacious in the treatment of skin diseases, despite the lack of evidence from randomized, double-blind, placebo-controlled trials. A major advantage of hdIVIg in comparison with other commonly used immunomodulating therapeutic strategies is the excellent safety profile. Accordingly, IVIgs have been used successfully for the treatment of bullous autoimmune diseases such as pemphigus and bullous pemphigoid, dermatomyositis, scleroderma, cutaneous lupus erythematosus, toxic epidermal necrolysis, and erythema exudativum multiforme. In most cases, hdIVIg is effective only in combination with other immunomodulating strategies and allows for the reduction of adjuvants. Adverse effects of hdIVIg are generally mild and self-limiting. These include headache, myalgia, flush, fever, nausea or vomiting, chills, lower backache, changes in blood pressure, and tachycardia. To avoid infusion-related rigors, headaches, and other adverse events, pre-treatment with analgesics, NSAIDs, antihistamines, or low-dose intravenous corticosteroids may be beneficial. Controlled, double-blind, long-term clinical trials and a better understanding of the complex immunomodulating mechanism of IVIg are required to ultimately optimize dose, frequency, duration, and mode of IVIg administration.

Autoimmune Diseases↗

Corticosteroids in diseases of the oral mucosa.

The introduction of corticosteroids into oral medicine heralded a therapeutic advance, and substantial benefits have occurred from their use. Three topical steroids are being used currently in oral diseases, i.e. hydrocortisone hemisuccinate, triamcinolone in Orabase 0-1 per cent and betamethasone valerate 0-1 mg. The efficacy of these agents can be increased markedly if they are administered during the prodromal phase of ulceration, i.e. when lymphocyte activity is at its maximum. Therapeutic doses of all of them can be exceeded three times without impairing adrenal function. Nevertheless some of these preparations, as exemplified by topical medication, induced an unfortunate acute pseudomembranous candidiasis without any alteration in the plasma cortisol level. The routine examination and treatment of ulcers in the mouth should be a careful exercise helped by a good light source and a tongue spatula. Oral lesions affecting the soft tissues may be often difficult to diagnose, because of the rapid occurrence of secondary changes, such as maceration from moisture, abrasion by food and teeth, perhaps, and the existence of erosions and ulcerations from ruptured vesicles or bullae. Thus, diagnosis will depend not only on the grouping and distribution of lesion, but also on its subsequent behaviour. In some cases too there will be associated changes in the facial skin or elsewhere in the body.

Administration, Topical↗

Canine immune complex diseases.

Though not conclusive, our primary findings indicate that a feature common to many of our tumor and ICD patients is depressed cortisol production. Additionally, the response to ACTH adrenal cortex stimulation tests, at 2-hour intervals between rest and stimulation, have ranged from negative to substantially less than would be expected in normal subjects. Peripheral plasma cortisol values for dogs, at rest and 2 hours after ACTH stimulation, respectively, have been reported as 2-10 and 25-30 mug/dl, 3-8 and 7.5-18 mug/dl, and 1-12.5 and 9.5-22 mug/dl. For representative patients, our resting values have been 1.2-5.2 mug/dl, vs 1.2-7.6 mug after ACTH stimulation (Table 2). Altogether we have studied 42 cases in detail, and we feel that a post-ACTH level of 8.0 mug/dl or less is a conservative indication of adrenocortical insufficiency; all levels have been between 1 and 8 mug/dl. We believe these low cortisol levels indicate either a genetically-induced adrenal cortical insufficiency (evident at 2 months to 1 year of age) or an immune complex adrenal cortical suppression (occurring after 1 year of age in association with other immunodeficiency disorders). Our studies demonstrate a need for biphasic therapy. We have found it necessary to not only initiate cortisone acetate therapy to support the deficient adrenal cortical secretion, but also use other immunosuppressive drugs to control the ICD. If the target organ has been suppressed or destroyed, the need for supplementation is obvious. However, other immune-injury moieties must be suppressed also, eg, ANA, anti-IgG antibodies, etc.

Animals↗

Immunosuppressive drugs in dermatology--benefits and threats.

Immunosuppression consists in the breaking of different immune reactions. According to the mechanism of activity, these drugs reveal effects on each stage of the immune process. Among immunosuppressive drugs, steroids, antimetabolites, alkylating agents, cyclosporine, mycophenolate mofetil are used in dermatology. Therapeutic potential of these drugs is limited by dangerous side effects. Apart from inhibition the excessive immunological response to antigens and because of the lack of specific action, they result in total suppression of the immune system. That in turn produces a higher number of infections, an abnormal course of diseases and an increased risk of lymphomas and cancers. Therefore, the decision, on applying any of these immunosuppressive drugs ought to be preceded by thorough analysis of the clinical history, indications and contraindications referring to each drugs and potential toxicity and side effects.

Connective Tissue Diseases↗

[Detection of immunoglobulin deposits in paraffin embedded skin with the peroxidase-antiperoxidase (PAP) method].

The peroxidase-antiperoxidase (PAP) technique allows the detection of immunoglobulin deposits in formalin-fixed, paraffin-embedded tissue. The PAP technique may be used as an alternative to the direct immunofluorescence method on frozen, unfixed skin. In addition, the PAP technique is suitable for retrospective evaluation of histological samples.

Fluorescent Antibody Technique↗