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Fever, lymphadenopathy, eosinophilia, lymphocytosis, hepatitis, and dermatitis: a severe adverse reaction to minocycline.

A 17-year-old female patient who had been taking oral minocycline (50 mg twice daily) for 3 weeks for acne developed an eruption that progressed to an exfoliative dermatitis. This illness was also characterized by fever, lymphadenopathy, pharyngitis, a leukemoid reaction, lymphocytosis, eosinophilia, hepatitis, and noncardiogenic pulmonary edema. Dramatic improvement followed institution of corticosteroid therapy. Studies for infectious and collagen vascular diseases were negative. This severe illness was likely caused by minocycline, and we speculate that minocycline may have acted as a superantigen, causing lymphocyte over-activation and massive cytokine release.

Acne Vulgaris↗

Familial opsonization defect associated with fatal infantile dermatitis, infections, and histiocytosis.

Members of four generations of a family had a defect of serum opsonization for yeast phagocytosis consistent with dominant inheritance. 2 were healthy, one had chronic osteomyelitis, and the fourth developed a fatal illness in infancy characterized by exfoliative dermatitis, diarrhoea, multiple bacterial infections, and failure to thrive, which resembled the two prevously reported cases with this opsonization defect. At necropsy the infant also had lymphoid depletion, which was possibly secondary, and massive histiocytic infiltration.

Adult↗

[Frequent dermatologic diseases in the newborn and children].

Sebaceous gland activity in the newborn and children is extensive at first in the epidermis, and later decreases owing to defective operation of the sweat glands, circulation changes, growth of the hair, and a predisposition to infection, for which significant treatment is required. In addition to the genetic "typus neurodermiticus", pharmaceutical, alimentary and respiratory allergens and psychological factors may play a part in the appearance of atopical dermatitis. Onset is usually in the 2nd to 6th month and the side of the face and the scalp are affected. The clinical picture varies considerably with age and includes sanious foci covered with scabs on the head and eczema flexurarum. Differences in family history, age and the location of sites will distinguish this form from seborrhoeic dermatitis. Gluteal dermitis is secondary to congestion caused by dampness, rugging and soaking, and the action of stools and urine (bacterial amniogenesis). The main complications of neonatal and infantile impetigo are: glomerulonephritis, exfoliative dermatitis, pulmonary abscess, pulmonitis and osteomyelitis; phlyctenular, serpiginous impetigo with large and small bullae is particularly important. Treatment of neonatal and infantile dermatosis must take account of the fact that increased reabsorption and congestion are contraindications for the local application of corticoids and preparations containing salicylic and boric acid.

Anti-Bacterial Agents↗

Neonatal staphylococcal scalded skin syndrome: massive outbreak due to an unusual phage type.

A massive outbreak of the staphylococcal scalded skin syndrome due to an organism with an unusual phage pattern, occurred during a 115-day period and involved 68 newborns. Generalized exfoliative dermatitis was seen in 24 babies, and Staphylococcus aureus was isolated from 23. Fourteen isolates were phage typed, with 13 reported as the epidemic strain 29/79/80/3A/3C/54/75. Eight babies had generalized scarlatiniform eruption without exfoliation (staphylococcal scarlet fever). Cultural data were available from six, all positive for S aureus. Four organisms were typed and reported as the epidemic strain. Of 34 infants with bullous impetigo 20 had cultures that were positive for S aureus, and four were phage typed, revealing the epidemic strain. Illness was mild in all patients; there were no deaths and no invasive forms of staphylococcal infection. The male to female ratio of generalized exfoliative disease was 5:1. The concept of a neonatal staphylococcal scalded skin syndrome, comprised of a triad of skin disorders induced by an exotoxin elaborated by certain strains of coagulase positive S aureus, is confirmed.

Disease Outbreaks↗

Lamotrigine-induced toxic epidermal necrolysis in three patients treated for bipolar disorder.

Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), is a mild-to-life-threatening process that has been described after exposure to many antiepileptic drugs. The increased use of antiepileptic drugs for treatment of bipolar disorder and neurologic disorders has extended the risk of exfoliative disorder to this population of patients, and these patients and their health care providers may not be familiar with the risks involved with these drugs. We describe the cases of a 28-year-old woman with bipolar 1 disorder initially treated with lamotrigine, and two adolescent girls with bipolar 2 disorder treated with lamotrigine after poor responses to other drug regimens. In all three patients, rashes progressed to toxic epidermal necrolysis in spite of treatment with corticosteroids at their local hospitals; thus, they were transferred to our burn treatment center. Response to early corticosteroid treatment in suppressing progression of exfoliation was variable in these patients. Ultimately, two of the three required ventilatory support; their conditions improved within 8-32 days of treatment, and they were discharged from the hospital. Case reports of lamotrigine-induced exfoliative disorder in patients with bipolar disorder have been published. However, these three patients were admitted to our burn treatment center within a 12-month period. Our institution admits approximately 10-12 patients with TEN/year, and the increased use of lamotrigine for treatment of bipolar disorder is likely to result in more patients with TEN. Therefore, health care professionals need to be aware of the early signs and symptoms of exfoliative dermatotoxicity when treating patients with lamotrigine.

Adolescent↗

Adverse reactions with oral and parenteral gold preparations.

Auranofin (triethylphosphine gold), an oral gold preparation, has recently been made available, and along with injectable gold preparations, is of therapeutic value for rheumatoid arthritis. Serious gold toxicity is uncommon, and drug-related deaths rare. Many potential adverse reactions are similar, including dermatitis, stomatitis, thrombocytopenia, leucopenia, and proteinuria, generally with increased incidence in the injectable gold-treated patients. Oral gold is associated with benign lower gastrointestinal side effects, including diarrhoea, loose stools and abdominal cramps that are often dose-related and resolve spontaneously. The incidence of severe reactions such as thrombocytopenia, aplastic anaemia and exfoliative dermatitis is lower with oral gold than injectable preparations, and contributes to a superior risk-benefit ratio. The treatment of gold toxicity depends on the type and extent of organ involvement.

Administration, Oral↗

Drug-induced skin disease.

Drug-induced cutaneous reactions encompass a wide variety of rashes that depend in part on route of administration (e.g., contact versus systemic) as well as type of cutaneous response and molecular mechanism underlying the reaction. One such reaction is a type IV immunologic reaction (delayed hypersensitivity) manifest as contact dermatitis and commonly elicited by drugs such as antihistamines, antibiotic ointments, local anesthetics, and paraben esters in cosmetic creams and lotions. A generalized eruption of this sort will occasionally occur with systemic administration of a drug to someone previously sensitized by topical application. Systemic administration of agents can cause nonspecific pruritus or maculopapular eruptions that resemble visual exanthemas. The pathogenesis is unclear and no immune mechanism has been demonstrated. If the drug is continued, exfoliative dermatitis can result. Other types of reactions are urticarial in nature and include acute urticaria/angioedema, erythema multiforme (bullous and nonbullous), Stevens-Johnson syndrome, urticaria in association with serum sickness-like reactions, and urticaria associated with anaphylactoid reactions. In many of these, an allergic reaction in which there is an immunoglobulin (Ig) E-dependent release of mediators in the skin causes hives or swelling. In others, circulating immune complexes may be present, often involving IgG antibody complexed with drug and complement fixation; hives may then be caused by anaphylatoxin release or a concomitant IgE-mediated reaction. In some instances, a cellular reaction may augment the aforementioned inflammatory reactions, perhaps as part of a late-phase reaction or a true delayed hypersensitivity component.

Angioedema↗

Dapsone hypersensitivity syndrome in an adolescent during treatment during of leprosy.

A 12 y old girl was admitted 24 days after start a WHO multidrug therapy scheme for multibacillary leprosy (dapsone, clofazimine and rifampicin) with intense jaundice, generalized lymphadenopathy, hepatoesplenomegaly, oral erosions, conjunctivitis, morbiliform rash and edema of face, ankles and hands. The main laboratory data on admission included: hemoglobin, 8.4 g/dL; WBC, 15,710 cells/mm3; platelet count, 100,000 cells/mm3; INR = 1.49; increased serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, direct and indirect bilirubin. Following, the clinical conditions had deteriorated, developing exfoliative dermatitis, shock, generalized edema, acute renal and hepatic failure, pancytopenia, intestinal bleeding, pneumonia, urinary tract infection and bacteremia, needing adrenergic drugs, replacement of fluids and blood product components, and antibiotics. Ten days after admission she started to improve, and was discharged to home at day 39th, after start new supervised treatment for leprosy with clofazimine and rifampicin, without adverse effects. This presentation fulfils the criteria for the diagnosis of dapsone hypersensitivity syndrome (fever, generalized lymphadenopathy, exfoliative rash, anemia and liver involvement with mixed hepatocellular and cholestatic features). Physicians, mainly in geographical areas with high prevalence rates of leprosy, should be aware to this severe, and probably not so rare, hypersensitivity reaction to dapsone.

Child↗

Clinical, histopathological and immunological characteristics of exfoliative cutaneous lupus erythematosus in 25 German short-haired pointers.

Clinical, histopathological and immunological features of exfoliative cutaneous lupus erythematosus, an uncommon generalized exfoliative dermatitis occurring exclusively in German short-haired pointers, were characterized in 25 dogs. The disease affects young adult dogs and its familial incidence strongly suggests a hereditary origin. Lesions were characterized by scaling and alopecia affecting 100 (25/25) and 76% (19/25) of dogs, respectively. Follicular casts were present in 28% (7/25) of dogs. The muzzle, pinnae and dorsum were typically affected. Generalized skin lesions were described in 52% (13/25) of dogs. Systemic signs of pain and lameness affected several dogs. Anaemia and thrombocytopenia were detected in several dogs with a more severe clinical phenotype. The most common histopathological features were hyperkeratosis and a lymphocytic interface dermatitis. Direct immunostaining revealed IgG deposition in the epidermal and follicular basement membrane of 100 (19/19) and 41% (7/17) of dogs, respectively. Circulating antifollicular and antisebaceous gland IgG antibodies were demonstrated by indirect immunostaining in 57% (4/7) of dogs. This disease usually responds poorly to immunosuppressive therapy and it has a guarded prognosis. Where outcome was recorded, 85% (10/12) of dogs were euthanased due to either a failure to respond to, or complications associated with, immunomodulatory therapy. Two affected dogs are in remission and maintained on immunomodulatory dosages of prednisolone. This study demonstrates the existence of a cellular and humoral immune response directed against the epidermal basement membrane of dogs with exfoliative cutaneous lupus erythematosus. Additional studies are required to further characterize the immunological pathogenesis of this disease.

Animals↗

Drug-induced liver injury. In vitro demonstration of hypersensitivity to both phenytoin and phenobarbital.

Fever, lymphadenopathy, exfoliative dermatitis, and evidence of drug-induced liver injury developed in a 16-year-old girl three weeks after beginning therapy with phenytoin and phenobarbital. This clinical syndrome can be caused by either of these structurally related drugs but has been more frequently attributed to phenytoin. In vitro studies disclosed marked reactivity of this patient's lymphocytes to concentrations of both drugs, which encompassed their measured serum levels. The demonstration of dual reactivity raises concerns about continuing administration of phenobarbital during an apparent phenytoin-induced reaction. Whether this potential risk is greater than the risk of stopping all anticonvulsant medications in a patient with a seizure disorder is not known and remains to be established.

Adolescent↗

Thalidomide in the treatment of patients with hepatocellular carcinoma: a phase II trial.

BACKGROUND: The treatment of patients with hepatocellular carcinoma (HCC) presents a major challenge, because associated cirrhosis limits the choice of chemotherapeutic agents. However, the abundant vascularity of HCC presents an attractive target for antiangiogenic therapy that potentially may be tolerated by cirrhotic patients. The current study was conducted to assess the antitumor activity, treatment tolerance, treatment-related toxicity, and patient survival after the administration of thalidomide in a Phase II trial. METHODS: Thirty-seven HCC patients were accrued between March, 1999, and March, 2000. Initially, the dose of oral thalidomide was escalated from 400 mg per day during the first week to 1000 mg per day by the fifth week, delivering one-third of the dose in the morning and the remaining two-thirds of the dose in the evening prior to bedtime. Changes in the daily drug administration schedule were allowed based on tolerance. Response was assessed at 8-week intervals. RESULTS: Thirty-two of 37 registered patients were evaluable for response. One patient had a partial response (PR), 1 patient had a minor response (MR), 10 patients had stable disease (SD) (31%; 95% confidence interval [95%CI], 16-51%), and 20 patients) (61%; 95%CI, 42-78%) had disease progression. The most commonly encountered toxicity was somnolence, with Grade 3-4 somnolence (>or= 4 hours of sleep during normal waking hours) in 9 patients (35%) and Grade 2 somnolence ( 800 mg if it was delivered at bedtime. Grade 3-4 skin reactions were observed in 20% of patients, and exfoliative dermatitis was observed in 1 responding patient. The overall median survival was 6.8 months. CONCLUSIONS: With a 5% PR rate, a 5% MR rate, and a 31% SD rate, the results indicate that thalidomide mostly may offer HCC patients disease stabilization. It is possible that, at a different dosage, or combined with other chemotherapy agents, or with the use of a different thalidomide analogue, longer patient survival may be achieved. However, in view of the significant neurologic toxicity encountered among these commonly cirrhotic HCC patients, thalidomide monotherapy at the high doses studied cannot be recommended for the treatment of HCC.

Adult↗

In vivo and in vitro suppression of T-cell receptor alpha/beta CD4- CD8- T lymphocytes by cyclosporine A.

We treated a patient with a combined immunodeficiency and disease pathology resembling GvHD with cyclosporine. This disorder was characterized by exfoliative dermatitis, lymphadenopathy, and lymphocytosis of a novel T-cell phenotype (CD3+ TCR alpha/beta+ CD4- CD8-). The patient's peripheral blood T cells had elevated cytolytic activity and expressed increased levels of IL2R, HLA-DR, and CD45RO. Treatment with CsA resulted in marked clinical improvement, resolution of the lymphocytosis, and reduced cytolytic activity of peripheral blood T cells. T-cell HLA-DR and IL2R expression was reduced by cyclosporine, but CD45RO remained intact on virtually all circulating T cells. CsA also inhibited the cytolytic activity and cytokine production of in vitro cultured TCR alpha/beta+ CD4- CD8- cell lines. Our data suggest that alleviation of the patient's clinical symptoms resulted from cyclosporine-mediated suppression of proliferation, cytotoxicity, and inflammatory cytokine production of TCR alpha/beta+ CD4- CD8- T lymphocytes in vivo. The response of this patient to cyclosporine, which was similar to that seen in true GvHD, provides further evidence that these conditions share common pathogenetic pathways.

CD4 Antigens↗

Amonafide treatment of refractory esophageal cancer. A Southwest Oncology Group study.

Amonafide, a synthetic benzisoquinolinedione, was evaluated for treatment of squamous esophageal cancer. Eleven men and 5 women were eligible with a median performance status of 1 and median age of 63 years. Six had no prior treatment. All patients had measurable disease. Therapy consisted of amonafide 300 mg/m2d days 1-5 every 21 days. Thirty-five courses of therapy were delivered. The median number of courses received was two. Sixteen patients are evaluable for toxicity. Thirteen are evaluable for response. Toxicity was severe. Seven patients were hospitalized for toxicity. Six patients had grade IV granulocytopenia; two, grade IV thrombocytopenia. Angioedema developed in one patient; severe exfoliative dermatitis in another. A single partial response, with the decrease in size a supraclavicular node, was noted in a previously untreated patient. Amonafide, in this dose and schedule, is associated with occasionally severe toxicity precluding its likely use in squamous cell esophageal carcinoma.

Adenine↗

Allopurinol in renal failure and the tumour lysis syndrome.

This paper illustrates several important points relating to the use of allopurinol in renal failure, or situations of purine overproduction: It is very easy to give too much allopurinol. Most of the side effects (bone marrow depression, exfoliative dermatitis, etc) are the result of overdosage due to the retention of oxipurinol, an effect exaggerated by thiazide diuretics. Monitoring of plasma oxipurinol levels (ideally less than 100 mumol/l) by high-pressure liquid chromatography is helpful for adjusting dosage in renal failure. Some estimate of the anticipated purine excess is equally vital in deciding dosage during tumour lysis if the risk of urate nephropathy is not to be substituted for the certainty of xanthine nephropathy. In this situation the use of allopurinol may even be questioned. Patients with HGPRT deficiency are exquisitely sensitive to allopurinol, and careful monitoring of the effect on urinary purine levels is essential if xanthine colic is to be avoided.

Adult↗

The staphylococcal scalded-skin syndrome versus erythema multiforme.

This article reports a case of scalded-skin syndrome in a young child. Characterized by a generalized exfoliative dermatitis resembling scalded skin, the disease may involve the oral mucosa and must be differentiated from Stevens-Johnson syndrome (erythema multiforme). Since the etiology is specific, the disease can be treated with antibiotics with dramatic results.

Administration, Oral↗