Drug hypersensitivity syndrome caused by minocycline

BACKGROUND: Minocycline is a commonly prescribed drug for the treatment of acne. Its use is generally not associated with systemic side effects. OBJECTIVE: To describe a case of minocycline-induced drug hypersensitivity syndrome in a 20-year-old Japanese woman. METHODS AND RESULTS: Following 2 months of minocycline treatment, the patient developed skin lesions composed of exudative maculopapules, purpuratous macules, and target-like, erythema multiforme-like plaques over most of her body. In addition, she had fever, abnormal liver function tests, eosinophilia, and atypical lymphocytosis. Laboratory tests indicated no elevation of antibody titers against cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6. Her ongoing exposure to minocycline was stopped, and treatment with oral prednisolone was begun. Her signs, symptoms, and laboratory abnormalities then began to resolve. Subsequently, the syndrome was observed to return briefly in response to an oral challenge with minocycline. CONCLUSIONS: Minocycline is able to elicit a drug hypersensitivity syndrome that can resemble infectious mononucleosis. This drug reaction can be treated effectively by cessation of exposure to this drug and steroid therapy.     

Minocycline hypersensitivity syndrome with hypotension mimicking septic shock

Minocycline is a semisynthetic tetracycline derivative that is often used in the treatment of acne vulgaris. A serious but rare adverse effect caused by minocycline therapy is a hypersensitivity syndrome (HS), consisting of fever, skin eruption, and internal organ involvement that begins within 8 weeks of therapy initiation. We report a case of minocycline HS with unique features, namely, associated hypotension, and a rebound of the cutaneous eruption upon discontinuation of systemic steroids.     

Erythema nodosum-like eruption as a manifestation of azathioprine hypersensitivity in patients with inflammatory bowel disease

BACKGROUND: Clinical manifestations of hypersensitivity to azathioprine may mimic symptoms of the initial disease. We report 5 cases of peculiar skin hypersensitivity reactions to azathioprine in patients with inflammatory bowel disease. OBSERVATIONS: In 5 patients with a recent azathioprine regimen, manifestations appeared between 8 and 18 days after drug introduction. All patients had a high fever. Three patients initially had erythema nodosum; 2 patients had sterile pustules. All had elevated neutrophil counts and serum C-reactive protein levels, whereas eosinophil counts were normal, ruling out drug-induced rash with eosinophilia and systemic symptoms. In 3 patients who were rechallenged with azathioprine or with 6-mercaptopurine, dermatological lesions recurred within hours. CONCLUSIONS: Erythema nodosum and pustules are rarely reported manifestations of azathioprine hypersensitivity. Both skin lesions may be related to the clinical activity of inflammatory bowel disease. Relapse of such lesions shortly after thiopurine rechallenge should raise the hypothesis of hypersensitivity rather than pharmacological manifestations.     

Diltiazem-induced acute generalised exanthematous pustulosis

Pustulation is a major feature in several different dermatoses, and it may also occur as a manifestation of drug: hypersensitivity. Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption characterized by acute, extensive formation of sterile pustules, fever and peripheral blood leucucytosis. It shares several clinical and historical features in common with pustular psoriasis. Most reported cases have been triggered by ingestion of broad spectrum antibiotics, particularly betalactams and macrolides. There is usually rapid resolution of the eruption on drug withdrawal. We report the case of a 58 year-old woman who developed AGEP shortly after commencing treatment with the calcium channel binder diltiazem hydro-chloride. The eruption followed a biphasic course, and improved following treatment with systemic corti-costeroids and methotrexate. AGEP appears to be a rare adverse cutaneous reaction to diltiazem, whereas a wide range of other skin eruptions have been reported more commonly with this drug.     

A case of acute generalized exanthematous pustulosis (AGEP) possibly induced by iohexol

Acute generalized exanthematous pustulosis (AGEP) is an uncommon disease manifested as an erythematous pustular eruption. It is usually caused by systemic medication. We describe a patient with acute generalized pustular eruption induced by iohexol. A 52-year-old woman developed fever and a generalized pustular eruption on the neck, trunk and extremities three days after taking iohexol. The culture from pustules was sterile. Other systemic and laboratory examinations were normal. A skin biopsy from a lesion on the trunk showed the features of a drug-induced pustular eruption as a subcorneal blister including neutrophils and eosinophils, mild spongiosis, and a sparse infiltrate at neutrophils and eosinophils in the papillary dermis. The patient had no history of psoriasis. The lesions resolved with systemic corticosteroid therapy within one week and did not relapse. According to our investigation, iohexol-induced AGEP has not been previously reported. We present an interesting case.     

Parvovirus B19 infection mimicking drug-induced hypersensitivity syndrome

BACKGROUND: Clinical manifestations of primary parvovirus B19 infection vary greatly. Epidermal megalerythema is the most common feature. We report a particular form resembling a drug-induced hypersensitivity reaction. CASE REPORT: A 19-year-old man had a scarlatiniform eruption associated with multiple node enlargement, elevated liver enzymes and a abnormal white cell count with mononucleosis and lymphopenia, similar to that observed in hypersensitivity reactions. Seroconversion and positive PCR search for viral DNA established the diagnosis of primary parvovirus B19 infection. The spontaneous course was favorable with no recurrence at one month. DISCUSSION: The clinical features and laboratory findings in this case of parvovirus B19 infection closely resembled drug-induced hypersensitivity syndrome. The role of viral agents in the development of hypersensitivity reactions have been suggested. It is important to look for viral infections in clinical presentations mimicking drug-induced hypersensitivity.     

Acute generalized exanthematous pustulosis in hypercalcemia

BACKGROUND: We report a case of typical exanthematous pustulosis rash that was particularly severe both clinically and biologically. Laboratory tests led to the diagnosis of acute parvovirus B19 infection. CASE REPORT: A 23-year-old man with no past medical history developed fever with an erythematous pustulosis rash predominantly involving the folds. Blood cell count revealed hyperleukocytosis. There was no previous drug intake. This skin reaction was associated with severe systemic manifestations including hypovolemic shock, and hematologic and metabolic disturbances. Virology tests revealed acute parvovirus B19 infection. The hospital physician caring for this patient also presented evidence of acute parvovirus B19 infection. DISCUSSION: The clinical features and the course of this skin eruption were typical of generalized exanthematous pustulosis. We discuss the rare viral causes of acute generalized exanthematous pustulosis and compare our case with a previously reported case of acute generalized exanthematous pustulosis with mononucleosic syndrome in a patient with no prior drug intake. The clinical and biological manifestations of this case were similar to drug hypersensitivity syndrome.     

抗惊厥药所致药物超敏综合征19例临床特征分析

目的：探讨抗惊厥药所致药物超敏综合征（DHS）的临床特征。方法：回顾分析19例抗惊厥药所致DHS患者的临床表现、实验室检查、治疗方法、并发症及预后。结果：抗惊厥药所致DHS潜伏期长,皮损形态多样,以发疹型为主,常伴有紫癜样斑疹、皮肤肿胀及反复脱屑,多有发热、黏膜损害、浅表淋巴结增大及血常规异常。脏器受累以肝脏为主,肾脏次之。糖皮质激素治疗有效。结论：DHS为具有特征性表现的临床综合征,病程较长,早期、足量地应用糖皮质激素有助于预后的改善。     

The anticonvulsant hypersensitivity syndrome

BACKGROUND: The anticonvulsant hypersensitivity syndrome is a potentially fatal multisystemic reaction to anticonvulsant medications. OBJECTIVES: The purpose of this study was to investigate the clinical characteristics of anticonvulsant hypersensitivity syndrome. RESULTS: A total 32 subjects, aged from 6 to 72 years, diagnosed as having anticonvulsant hypersensitivity syndrome based on clinical and histopathological findings, were included in the study. In 22 of the 32 cases, the anticonvulsants had been administered prophylactically after craniotomy and in 10 cases for epilepsy. When the cases were assessed for skin lesions, maculopapular eruption was registered in 22, Stevens-Johnson syndrome in five, and toxic epidermal necrolysis (TEN) in five. Treatment included suspension of the offending drug and then, except for the cases with toxic epidermal necrolysis, administration of corticosteroids. The 22 cases that required anticonvulsant therapy were treated with valproic acid. In all cases, we observed rapid clinical improvement corroborated by laboratory findings. CONCLUSIONS: It is essential that due importance be given to the development of an eruption in individuals to whom anticonvulsants are administered after craniotomy because anticonvulsant hypersensitivity syndrome is likely to be life-threatening.     

Patch testing is an effective method for the diagnosis of carbamazepine‐induced drug reaction,eosinophilia and systemic symptoms (DRESS) syndrome in an 8‐year‐old girl

Drug reaction, eosinophilia and systemic symptoms (DRESS) is an acute and life‐threatening disease, characterised by fever, rash and systemic symptoms, including lymphadenopathy, abnormal liver function, interstitial nephritis, pulmonary and cardiac infiltrates and haematological abnormalities with eosinophilia and atypical lymphocytes. The drugs mostly associated with DRESS are anticonvulsants, allopurinol, minocycline and sulfonamides. This syndrome is rarely seen in childhood even though a large number of children have anticonvulsant treatment. An 8‐year‐old girl was admitted with fever, lymphadenopathy and skin eruptions on her trunk. Her medical history was notable for epilepsy and carbamazepine treatment had been started 5 weeks previously. Laboratory studies showed a white cell count of 6200/µL (normal, 4100–11 200/µL) with 22% eosinophils and a γ‐glutamyl transpeptidase level of 296 U/L (normal, 0–23 U/L). Laboratory tests for infections and collagen diseases were in the normal range. Persistence of fever and maculopapular eruption with generalised desquamation and the appearance of cheilitis and facial angioedema suggested a hypersensitivity reaction to carbamazepine. The carbamazepine was replaced with levetiracetam. All clinical symptoms improved within a week with corticosteroids and antihistamine treatment. Six weeks after complete recovery an epicutaneous patch test with carbamazepine was performed and a carbamazepine‐induced positive skin reaction was observed at 48‐h. Carbamazepine‐induced DRESS syndrome is a rare entity in children. An epicutaneous patch test is a useful tool for identifying the inducing agent for the DRESS syndrome and for identifying a safe anticonvulsant drug.     

The use of tetracyclines for the treatment of sarcoidosis

BACKGROUND: To evaluate the safety and efficacy of minocycline in the treatment of sarcoidosis, a nonrandomized, open study was performed in patients with cutaneous sarcoidosis. OBSERVATIONS: Twelve patients with cutaneous sarcoidosis were treated with minocycline, 200 mg/d, for a median duration of 12 months. Three patients had extracutaneous lesions at the time of the study. The median follow-up was 26 months. A clinical response was observed in 10 patients, consisting of complete responses in 8 patients and partial responses in 2 patients. A progression of skin lesions was observed in 1 patient, and lesions remained stable in another patient. Adverse effects were minimal, except in 1 patient, who developed hypersensitivity syndrome. A slight hyperpigmentation occurred in 2 patients at the site of previous lesions, which completely disappeared after minocycline use was discontinued. A relapse of skin symptoms occurred after minocycline withdrawal in 3 patients, who further received doxycycline, 200 mg/d, allowing a complete remission of lesions. CONCLUSIONS: These results support that minocycline and doxycycline may be beneficial for the treatment of cutaneous sarcoidosis. Randomized controlled studies are warranted for the evaluation of the true efficacy of tetracyclines in these patients.     

Sweet's syndrome and phenylbutazone-induced sialadenitis

BACKGROUND: Phenylbutazone frequently induces a range of potentially dangerous adverse reactions. We report a case of Sweet's syndrome with sialadenitis induced by phenylbutazone. CASE-REPORT: A 54-year-old woman presented lumbar pains treated with phenylbutazone for three days. Six days later, she exhibited inflammation of the submaxillary and parotid salivary glands, followed by an erythematous, oedematous, pustular and febrile eruption, with failure of antibiotic therapy. Laboratory data showed leukocytosis and neutrophilia, anaemia, an elevated platelet count and liver dysfunction. The infectious and autoimmune tests were negative. The skin biopsy confirmed Sweet's syndrome. Clinical and biological abnormalities resolved on administration of systemic steroids. DISCUSSION: Phenylbutazone-induced sialadenitis is rare and presents unrecognized adverse effects that may be associated with a systemic reaction. In the present case report, Sweet's syndrome met the criteria for drug-induced Sweet's syndrome. There appears to have been a systemic reaction caused by a hypersensitivity mechanism, in the same way as sialadenitis.     

Allergic contact dermatitis from natural latex without contact urticaria

During the test decade, there have been many reports of immediate-type hypersensitivity to natural latex, resulting in contact urticaria, generalized allergic read ions such as urticaria and Quincke's edema, and asthmatic or anaphylactic reactions. Moreover, delayed-type hypersensitivity to rubber additives such as thiuram and carbamate derivatives is acknowledged to be the main cause of dermatitis in patients working with rubber gloves. We here report on a patient who developed severe dermatitis on his hands and forearms 3 months after he had started working with rubber gloves. Patch tests with rubber additives, skin prick tests and RAST to natural latex were negative. However, a delayed type of hypersensitivity to latex could be shown by a positive patch test. To our knowledge this is the 1st case reported of an isolated contact dermatitis from natural latex without contact urticaria to latex or hypersensitivity to rubber additives. We therefore propose that not only patch tests with rubber additives, hut also skin prick and patch tests with latex should be performed in contact dermatitis patients working with rubber gloves.     

Dapsone hypersensitivity syndrome with circulating 190‐kDa and 230‐kDa autoantibodies

Dapsone has potent anti‐inflammatory effects, and is used in the treatment of leprosy, cutaneous vasculitis, neutrophilic dermatoses, and dermatitis herpetiformis and other blistering disorders. However, it may cause severe adverse reactions such as hypersensitivity syndrome, which is characterized by fever, skin rash, hepatitis and lymphadenopathy. We report a 44‐year‐old female Korean patient with dapsone hypersensitivity syndrome (DHS) that presented as a bullous skin eruption. The patient had a 1‐year history of urticarial vasculitis, treated with antihistamines, prednisolone and dapsone. Although the skin lesions improved, she reported fever, nausea, abdominal pain, jaundice, fatigue and skin rashes. On physical examination, there were generalized erythematous macules and purpura with facial oedema that developed into vesicles on the upper limbs. Histological examination of a skin biopsy of a vesicular lesion found subepidermal oedema with a mixed inflammatory cell infiltrate, including eosinophils in the dermis. Indirect immunofluorescence testing using normal foreskin as substrate revealed IgG deposits in the basement membrane zone. Circulating autoantibodies against antigens of 190 and 230 kDa were found by immunoblotting analysis using epidermal extracts. This case illustrates DHS with the formation of circulating autoantibodies.     

Life-threatening acute adverse cutaneous drug reactions

Adverse cutaneous reactions to drugs are frequent, affecting 2% to 3% of all hospitalized patients. Fortunately, only about 2% of adverse cutaneous reactions are severe and very few are fatal. Stevens-Johnson syndrome and toxic epidermal necrolysis are severe life-threatening diseases with a mortality rate reaching 30%, and only prompt recognition and diagnosis, withdrawal of the offensive drug, and referral to an intensive care unit or burn care unit might improve the prognosis and save the patient's life. Drug eruption with eosinophilia and systemic symptoms syndrome, formerly termed drug hypersensitivity syndrome, is a rather distinct severe adverse drug reaction (ADR) characterized by eruption, fever, lymph node enlargement, and single or multiple organ involvement, with a high morbidity and a mortality rate of 10%. These severe ADRs, together with serum sickness-like syndrome, are discussed in this review. Other severe reactions, such as anaphylaxis and vasculitis, are discussed elsewhere in this issue. Although most of the readers, particularly those in the outpatient arena, will not be treating these patients, they are the ones who will see them first, diagnose them, realize the potential danger in their condition, and refer them to the appropriate treatment venue. Therefore, dermatologists should be familiar with these conditions and be prepared to handle them adequately.     

The phenytoin syndrome

Five cases of the phenytoin syndrome are reviewed here. This hypersensitivity reaction is characterized by fever, eruption, lymphadenopathy, and hepatitis. Anemia, pharyngitis, diarrhea, and nephritis may also be associated. The skin eruption is pleomorphic, presenting as morbilliform eruptions, follicular papules and pustules, erythroderma, or toxic epidermal necrolysis. The management of these patients is made more difficult by the tendency for multiple relapses even after the use of phenytoin has been discontinued.     

Study of the clonality of cutaneous and blood lymphocytes during drug-induced hypersensitivity in 6 patients

INTRODUCTION: The drug-induced hypersensitivity syndrome or DRESS (drug reaction with eosinophilia and systemic symptoms) is a severe toxiderma because it is accompanied by lethal visceral involvement in 6 to 10% cases. Its physiopathology remains unclear. In order to specify the immunological characteristics of this toxiderma we analyzed, prospectively, the rearrangement of the blood and cutaneous T-cell lymphocyte receptor (TCR) genes of patients exhibiting a drug-induced hypersensitivity syndrome between April 1998 and April 2000. PATIENTS AND METHODS: The inclusion criteria were: age over 18 years, occurrence of a drug-induced generalized eruption, existence of associated systemic involvement (lymph node or visceral), and presence of hypereosinophilia greater than 0.5 G/l and/or circulating atypical lymphocytes. Six patients (3 men and 3 women), with a mean age of 54 years were included. The imputable drug was an anti-seizure in 3 cases, allopurinol in 2 and oxazepam in one. Remission occurred within a delay of 10 to 30 days after the acute phase. Two patients presented several flares. RESULTS: No clonal rearrangement in TCR genes was detected in the cutaneous samples. A clonal rearrangement of TCR genes was initially detected in the blood lymphocytes of 3 out of the 6 patients (allopurinol: n=2 and oxazepam: n=1). The latter remained detectable during the evolution, during the second or third flare of the drug-induced hypersensitivity in 2 patients (allopurinol: n=1 and oxazepam: n=1). DISCUSSION: The presence of circulating T-cell clones detectable for several months after the occurrence of a drug-induced hypersensitivity shows the mono or oligoclonal expansion of activated T-cells, induced by the drug imputed. Their persistence over several months corresponds to a remnant activation of the immune system that can explain the prolonged and/or recurrent evolution of the drug-induced hypersensitivity syndrome in some patients.     

Drug eruptions from mesna. After cyclophosphamide treatment of patients with systemic lupus erythematosus and dermatomyositis.

BACKGROUND--Mesna is used to abolish urotoxicity of cyclophosphamide and related compounds in immunosuppressive and antineoplastic treatment schedules. Adverse reactions to this drug have been reported only rarely. OBSERVATIONS--Drug eruptions to mesna have developed in seven of 15 patients with autoimmune disorders treated with monthly pulses of intravenous cyclophosphamide. Two different types of drug eruptions were observed: five patients had development of a macular and partly papular or urticarial rash and angioedema and two patients had a generalized fixed drug eruption, primarily and predominantly at the sites of previous skin lesions of their underlying condition. The results of prick, patch, and intradermal tests were similar in both types of rash; however, the two patients with fixed drug eruption had developed a generalized eruption upon prick testing with mesna. CONCLUSIONS--Two distinct eruptions to mesna have been induced in these patients during cyclophosphamide/corticosteroid therapy; these eruptions are not thought to share a common pathogenic mechanism. The results of skin and challenge tests do not support the hypothesis that a type 1 or a type 4 immune reaction may be responsible for these eruptions. The unusually high incidence (about 50%) of these reactions and their clinical presentation make it important to distinguish them from an exacerbation of the preexistent autoimmune disorder.     

Hypersensitivity reaction in a child due to lamotrigine

Lamotrigine is an anticonvulsant with a broad spectrum of activity that has been approved in the United States for use in adults with either partial or generalized seizures. This drug is being widely prescribed by pediatricians and neurologists because it is effective in children with idiopathic, resistant, generalized seizures and does not impair cognition. As with other anticonvulsants, a hypersensitivity syndrome has been described. Anticonvulsant hypersensitivity syndrome consists of the hallmark features of fever, rash, and lymphadenopathy. We report the first case of hypersensitivity syndrome in a child due to lamotrigine in which we believe the coadministration of valproic acid increased the duration of the reaction. Our patient had a high spiking fever, generalized morbilliform eruption, facial edema, lymphadenopathy, eosinophilia, atypical lymphocytosis, and an elevation in his liver function tests. The syndrome resolved with the discontinuation of the medication. Anticonvulsant hypersensitivity syndrome may occur with the administration of lamotrigine. Variable presentations may be seen, as hypersensitivity syndromes may be multisystem in nature. The prompt recognition of the signs and symptoms of this condition allows an accurate diagnosis so that the drug may be discontinued and other anticonvulsant treatment options instituted.     

Carbamazepine-induced hypersensitivity syndrome occurring in a photodistributed pattern

A 76- year- old man was commenced on carbamazepine for partial seizures. This was followed by the development of a rash in an apparently photodistributed pattern, fever, lymphadenopathy, eosinophilia, abnormal liver function tests and atypical lymphocytosis fulfilling the criteria for drug-induced hypersensitivity syndrome. Discontinuation of carbamazepine and application of topical steroid resulted in clearance of the rash, normalization of liver function tests and improvement in eosinophilia. The photodistributed pattern in this case of carbamazepine-induced hypersensitivity syndrome is of interest.