Mucocutaneous Eruption Research Articles

Drug-Induced Severe Skin Reactions

Severe skin adverse drug reactions can result in death, but the rate of such events is fortunately low. The incidences of Stevens-Johnson syndrome and toxic epidermal necrolysis range from 1.2 to 6 per million per year and 0.4 to 1.2 per million per year, respectively. Stevens-Johnson syndrome is fatal in about 5% and toxic epidermal necrolysis in 30% of cases. Drugs implicated in these diseases are the sulphonamides, anticonvulsants, allopurinol, pyrazolone derivatives, oxicams and chlormezanone. The principles of symptomatic treatment are the same as for burns, and patients with extensive skin detachment should be transferred to an intensive care unit or a burn centre. Hypersensitivity syndrome is characterised by mucocutaneous eruption and fever with frequent lymphadenopathy, hepatitis and eosinophilia. Drugs implicated are mainly anticonvulsants and sulphonamides. The mortality rate of such a reaction has been estimated to be about 8%. Corticosteroid therapy has been widely used in hypersensitivity syndrome, despite the lack of controlled studies. Drug-induced vasculitis and serum sickness may also be life-threatening when the kidney, liver, gastrointestinal tract or nervous system are involved. In angioedema, congestion may involve mucous membranes and therefore impair swallowing and ventilation. Drugs associated with angioedema include penicillins, radiographic contrast agents and ACE inhibitors. Severe forms of angioedema necessitate epinephrine (adrenaline) subcutaneous injection and possibly resuscitative efforts. Corticosteroids and/or antihistamines are used to block or reduce prolonged or late phase reactions. Prompt recognition and withdrawal of the suspected drug is essential in severe drug-induced skin reactions.

Acanthosis nigricans.

Acanthosis nigricans is a mucocutaneous eruption that occurs in a strikingly exuberant form as a marker for a highly malignant and rapidly fatal internal cancer. Recently, it has been recognized that acanthosis nigricans may also be a relatively common marker for increased long-term risk of the less dramatic but potentially serious systemic disorders associated with insulin resistance and compensatory increased insulin secretion.

Paraneoplastic pemphigus in a child with a T-cell lymphoblastic lymphoma

We report a child with a T-cell lymphoblastic lymphoma, and a widespread erosive mucocutaneous eruption, whose clinical and immunopathological features were consistent with a diagnosis of paraneoplastic pemphigus. Direct immunofluorescence showed deposition of C3 in the epidermal intercellular spaces, and in a linear pattern along the dermo-epidermal junction. Circulating autoantibodies binding in a pemphigus-like pattern to mouse urinary bladder epithelium were found. By Western immunoblotting, the patient's serum recognized two epidermal polypeptides with molecular weights of 210 and 190 kDa. No reactivity with the 230-kDa bullous pemphigoid antigen and the 250-kDa desmoplakin I antigen was found.

Histologic Features of Paraneoplastic Pemphigus

We describe the histopathologic features of paraneoplastic pemphigus, a recently described autoimmune mucocutaneous disease associated with neoplasia. Complete evaluation for paraneoplastic pemphigus requires identification of the characteristic mucocutaneous eruption, tissue specimens for routine histologic and direct immunofluorescence evaluation, and identification of circulating autoantibodies with a unique specificity. Immunoprecipitation from keratinocytes reveals a characteristic complex of four proteins with the circulating antibodies. Various neoplasms have been identified in patients with paraneoplastic pemphigus. We reviewed 16 skin and oral mucous membrane biopsy specimens from six patients with paraneoplastic pemphigus confirmed by fulfillment of all criteria. Major features include epidermal acantholysis, suprabasal cleft formation, dyskeratotic keratinocytes, vacuolar change of the basilar epidermis, and epidermal exocytosis of inflammatory cells. Seven (44%) of 16 specimens displayed a unique combination of suprabasal acantholysis and dyskeratotic keratinocytes throughout the epidermis. These histologic findings correspond to those of the characteristic clinical lesions that are described as having features of pemphigus and erythema multiforme. Paraneoplastic pemphigus represents a unique clinical, histologic, and immunologic disease characterized by autoantibody production to desmoplakin I and desmoplakin II, bullous pemphigoid antigen, and, possibly, other antigens in the desmosomal complex. Recognition of the histologic features should prompt immunopathologic confirmation and evaluation for an occult neoplasm.

The Overdiagnosis of Erythema Multiforme

To the Editor.— Erythema multiforme (EM) is an acute, self-limited mucocutaneous eruption characterized by the abrupt onset of symmetrical, fixed, red papules, some of which evolve into target lesions, the hallmark of EM.1 Since the original description by Ferdinand von Hebra in 1860, there has been confusion regarding the diagnosis.2 From children referred for a National Institutes of Health-sponsored research study of EM, we noted that a large majority of the children did not meet the criteria for EM.1

Paraneoplastic Pemphigus With Autoantibody Deposition in Bronchial Epithelium After Autologous Bone Marrow Transplantation

Paraneoplastic pemphigus is a newly described syndrome in which patients have a severe mucocutaneous eruption with clinical features reminiscent of both erythema multiforme major (Stevens-Johnson syndrome) and pemphigus vulgaris, in association with non-Hodgkin's lymphomas and other malignant neoplasms. These patients have autoantibodies that bind to a characteristic set of epidermal proteins: desmoplakin I and desmoplakin II (molecular weight equals 250 kd and 210 kd, respectively), both major cytoskeletal structural proteins associated with desmosome cellular junctions within all epithelia, the bullous pemphigoid antigen, a 230 kd protein associated with hemidesmosomes, and a 190,000-d protein that has not been characterized. In this report, we describe a patient with paraneoplastic pemphigus who had (1) non-Hodgkin's lymphoma in apparent complete remission following autologous bone marrow transplantation, (2) very tense blisters reminiscent of bullous pemphigoid, (3) a unique pattern of immune deposits within the skin, and (4) IgG deposits within the epithelium of the pulmonary bronchi associated with respiratory compromise.

Dermatologic complications associated with administration of 2′,3′-dideoxycytidine in patients with human immunodeficiency virus infection

We describe a distinctive mucocutaneous eruption that occurred in 14 of 20 (70%) patients with human immunodeficiency virus infection while they were being treated with a new therapeutic agent, 2'3'-dideoxycytidine. A maculopapular eruption developed in these patients on day 10 or 11 of treatment. Seven of 14 patients, especially those receiving higher-dose therapy, also had systemic symptoms. In addition, oral ulcers developed in 9 of 14 patients on days 4 to 6 of therapy. The occurrence of the cutaneous and oral lesions correlated with dose, route, and schedule of administration of 2'3'-dideoxycytidine. In most instances the mucocutaneous lesions resolved even with continuation of therapy.

Mucocutaneous manifestations of HIV infection

The acquired immunodeficiency syndrome (AIDS) has been associated with mucocutaneous eruptions since it was first described with Kaposi's sarcoma as a diagnostic criterion. 1 Human immunodeficiency virus (HIV), the etiologic agent of AIDS, is associated with a wide spectrum of clinical disorders. These conditions range from asymptomatic infection to AIDS-related complex or AIDS. 2 Mucocutaneous eruptions associated with HIV infection are common and frequently occur before the development of AIDS. 3–5 Although cutaneous manifestations are not the direct result of HIV infection, the majority of these eruptions are associated with immunosuppression. The common denominator of the immunosuppressed state resulting from infection with HIV is the infection and destruction of the helper/inducer subset of T-lymphocytes that express the CD4 receptor. 6 As immune function progressively deteriorates, opportunistic infections and malignancies evade immune surveillance resulting in clinical disease. Eruptions occurring in atypical distributions or in severe or chronic forms should alert the physician to the possibility of underlying HIV infection. In many instances, these eruptions are very difficult to manage and are frequently resistant to standard medical therapy. The mucocutaneous manifestations associated with HIV infection can be divided into three categories: (1) infections, (2) neoplasms, and (3) miscellaneous (Table 7-1).

Mucocutaneous reactions to antineoplastic agents.

Mucocutaneous reaction patterns in patients receiving cancer therapy are not only variable, but in many instances identical patterns are produced by different pathologic mechanisms. For example, patients with leukemia or lymphoma may present with nodular skin lesions that may represent malignant infiltration, septic emboli, vasculitis, or a drug eruption. The most banal skin eruption may signal an impending or ongoing catastrophe. If one is able to make some clinical evaluation regarding the likelihood of a drug being responsible for the mucocutaneous eruption, it may help avoid further clinical or laboratory investigation and patient discomfort. Unfortunately, only a few antineoplastic agents have "characteristic" skin manifestations. If, however, these are kept in mind they may be helpful in the diffential diagnosis of mucocutaneous eruptions occurring in patients treated with cancer chemotherapeutic agents.

Mucocutaneous eruptions due to antiepileptic drug therapy in children

Three children with bullous erythema multiforme and 1 with toxic epidermal necrolysis associated with antiepileptic drug therapy are described. One patient is unique because of seven mucocutaneous eruptions caused by three classes of antiepileptic drugs. Lymphocyte stimulation by antiepileptic drugs could not be demonstrated in the 2 patients in whom appropriate studies were performed, and no precipitating antibodies to antiepileptic drugs were found. Observation of four diagnostic and therapeutic principles, which are illustrated by the course of our patients, may reduce the incidence of life-threatening mucocutaneous eruptions and simplify the long-term management of individuals in whom such reactions occur.

Localized odontalgia occurring during herpes zoster of the maxillary division of the fifth cranial nerve: Report of a case

We have presented a case in which severe pain of the right lateral maxillary incisor occurred in association with herpes zoster of the ipsilateral maxillary nerve. The tooth was basically free of disease, and the pain remitted spontaneously following the healing of the mucocutaneous eruptions. It is thought that odontalgia may be an unusual manifestation of herpetic neuritis.