Severe drug rash with eosinophilia and systemic symptoms after treatment with minocycline

Introduction

Lung involvement is rarely observed in the DRESS syndrome (Drug rash with eosinophilia and systemic symptoms). We report here a severe minocycline induced hypersensitivity syndrome with initial respiratory distress.

Case report

A 19 year old man was admitted to the intensive care unit for acute respiratory distress with fever (40⁰C), lymph node enlargement, hepatomegaly, splenomegaly and eosinophilia (1640/mm³). Bilateral alveolar opacities were observed on the chest x-ray. Sedation and mechanical ventilation rapidly became necessary because of severe hypoxaemia (47 mm Hg) and the sudden onset of severe aggressive behaviour. The diagnosis of DRESS was immediately suspected as the patient had been treated for acne with minocycline for 28 days, and IV corticosteroids (2 mmg/kg/day) were initiated. Skin lesions were delayed and appeared 3 days later. The outcome was uncertain for the following 6 weeks with serious disturbance of hepatic and renal function. Serology for human herpes virus (HHV6) was initially negative but became positive. One year later, after progressive withdrawal of corticosteroid therapy, the patient had made a complete recovery with no sequelae.

Conclusion

The DRESS syndrome can cause considerable morbidity with multiple, severe visceral functional disturbances. Respiratory physicians should be aware of this syndrome as lung involvement can be serious and may precede cutaneous symptoms.     

Acute Liver Injury in the setting of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome with Cocaine as suspected culprit agent: A case report

Drug Reaction with Eosinophilia and Systemic Response (DRESS) syndrome is a rare hypersensitivity reaction characterized by rash, fever, lymphadenopathy, and visceral involvement. The liver is frequently involved in DRESS, with increased liver enzymes and hepatomegaly. Over 40 drugs have been implicated in the induction of DRESS, however other illicit substances have also been linked to this. Prompt identification of this syndrome is imperative for management. We report the case of patient presenting with acute liver injury and eosinophilia, who developed a rash meeting criterion for DRESS, with Cocaine as the suspected culprit agent, and was successfully treated with conservative measures.     

Laryngeal edema in drug reaction with eosinophilia and systemic symptoms syndrome due to sulfasalazine

We present a case of a 47-year-old man with drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. The patient had been diagnosed with rheumatoid arthritis and sulfasalazine was prescribed 4 weeks before admission. Initial symptoms with fever and rash worsened even after a discontinuation of the medication, and concomitant symptoms developed including typical manifestations of facial rash and edema sparing the periorbital area, as well as atypical laryngeal edema. Rheumatologists should be aware that sulfasalazine is derived from sulfonamide and can possibly induce DRESS syndrome, one of the life-threatening drug eruptions.     

Successful treatment with sodium valproate of a patient with Cushing's disease and gross enlargement of the pituitary

Transfrontal hypophysectomy was performed in a patient with Cushing's disease and gross enlargement of the pituitary. Despite some reduction of cortisol production active Cushing's syndrome remained due to the presence of a tumour remnant. Medical treatment with the GABA-transaminase inhibitor sodium valproate induced hypocorticism necessitating corticosteroid substitution therapy. Nine months after sodium valproate withdrawal hypercorticism was documented. Re-institution of sodium valproate treatment induced hypocorticism again. As sodium valproate is known to induce a decrease of plasma ACTH in Nelson's syndrome, it is proposed that large tumours present at the time of diagnosis and those appearing after adrenalectomy may represent the spectrum of a single disorder. A prospective trial to study the effects of sodium valproate and other neurotransmitter modulating agents on the size and endocrine function of ACTH secreting macroadenomas is urgently needed.     

A case of Münchausen syndrome with recurrent bacteremia and PR3-ANCA positivity

A 29-year-old woman chiropractor with repeated episodes of bacteremia and positive for cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) and antiproteinase-3 (PR3) antibody had an 11-year history of asthma and repeated hospitalization. While hospitalized she developed a spiking nocturnal fever with chills and erythema of the lower leg. Her fever resolved spontaneously, but corticosteroid therapy and antibiotics did not effectively reduce her symptoms. Plain X-ray film and CT showed pulmonary changes, and lung biopsy granulomas without vasculitis. Immunological studies showed a positive PR3-ANCA (c-ANCA) test, and skin biopsy of the crural erythema showed foreign body granuloma. Multiple blood cultures were positive for several strains of bacteria, including Fusobacterium necrophurum, Mycobacterium fortuitum, and Clostridium species. When placed in a single room and monitored, she did not develop new fever or erythema. Because self-injury was assumed, she was diagnosed as having Münchausen syndrome. This is, to our knowledge, the first report of Münchausen syndrome with PR3-ANCA positivity. In patients with repeated infections, the possibility of self-injury, the development of PR3-ANCA positivity, and pulmonary granuloma with a disease profile similar to vasculitis syndrome should be considered in the definitive diagnosis.     

Case report: Brucellosis: a re-emerging disease in Thailand

Brucellosis is a zoonotic disease prevalent in many countries, but it has been reported only once in Thailand, 36 years ago. We describe here two consecutive cases of brucellosis in Bangkok, Thailand. Both cases presented with prolonged fever and weight loss. Blood cultures taken from 2 patients yielded Brucella melitensis. The slide agglutination test of blood samples were also positive, with a titer of 1:64 for antibodies to Brucella. The first patient responded to a combination of doxycycline, gentamicin, and ciprofloxacin; the other responded to doxycycline and rifampicin. Brucellosis is a potential public health threat, therefore, preventive measures should be actively implemented. This clinical syndrome should be included in the differential diagnosis of patients presenting with prolonged fever, particularly those with contact to animals which could serve as reservoirs.     

Endocarditis associated with antineutrophil cytoplasmic antibodies: a case report and review of the literature

We report a case of subacute bacterial endocarditis associated with small vessel vasculitis and a strongly positive cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) test. It is important to recognize this cause of positive c-ANCA because infectious endocarditis may closely mimic the clinical manifestations of ANCA-associated vasculitides such as Wegener granulomatosis or microscopic polyangiitis. Furthermore, ANCA-associated vasculitis may result in noninfectious endocarditis, which may be confused with bacterial endocarditis. In this paper, we review reported cases of ANCA-positive bacterial endocarditis and compare them to the reported cases of ANCA-associated idiopathic vasculitis with endocardial compromise. Julio A. Chirinos and Vicente F. Corrales-Medina contributed equally in the preparation of this manuscrip     

Streptococcal viridans subacute bacterial endocarditis associated with antineutrophil cytoplasmic autoantibodies (ANCA)

We report an illustrative case of a 60-year-old man with Streptococcus viridans subacute bacterial endocarditis (SBE) and positive antineutrophil cytoplasmic autoantibodies (c-ANCA). C-ANCA positivity has been associated with a variety of rheumatic and infectious disease areas, but has been rarely associated with SBE. The patient had mitral valve prolapse with mitral regurgitation, and S viridans SBE developed after a dental procedure. Laboratory abnormalities included anemia, elevated erythrocyte sedimentation rate, positive rheumatoid factor, positive anticardiolipin antibody, positive lupus anticoagulant, and highly elevated c-ANCA level. We believe this is only the ninth reported case of S viridans SBE with a positive c-ANCA, and the third with mitral valve prolapse and vegetations.     

The importance of vancomycin in drug rash with eosinophilia and systemic symptoms (dress) syndrome

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome characterized by fever, rash, eosinophilia, atypical lymphocytes, and multiorgan involvement has a significant mortality. Inpatient vancomycin use is increasing and appears to be emerging as an important etiology of DRESS syndrome. This study highlights the importance of vancomycin as a cause of DRESS syndrome. We reviewed all cases of DRESS syndrome among inpatients consulted by the Allergy & Immunology service at Massachusetts General Hospital (MGH) from July 2009 through December 2010. We also reviewed the use of inpatient parenteral vancomycin over the past 4 years at MGH. Six patients fulfilled clinical criteria for DRESS syndrome, including rash, fever, eosinophilia, and hepatitis, with five (83%) having vancomycin as the attributable cause. Onset of symptoms varied from 12 days to 4 weeks after start of vancomycin treatment. Systemic findings included atypical lymphocytes, lymphadenopathy, nephritis, hypotension, tachycardia, and pharyngitis. Treatment with corticosteroids was required in three cases. Recurrence of peripheral eosinophilia was a marker of disease relapse. In three of the five patients (60%), elevated human herpesvirus 6 (HHV6) IgG titers correlated with greater systemic involvement and prolonged time to resolution. MGH pharmacy records indicate a progressive increase in the number of patients treated with parenteral vancomycin over the last 4 years. Causative agents for DRESS syndrome in an inpatient setting is likely different from that seen in the general population. With increasing use of vancomycin, we are likely to see more cases of DRESS syndrome caused by vancomycin. Recognition of vancomycin as a common cause of inpatient DRESS syndrome is important.     

A successful pregnancy and delivery case of Graves' disease with myeloperoxidase antineutrophil cytoplasmic antibody induced by propylthiouracil

A 30-year-old female patient, diagnosed as having Graves' disease in 1996, was treated with propylthiouracil (PTU) for 4 years. She developed a low-grade fever from December 1999. As myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) vasculitis is one of the adverse effects of PTU, we examined serum MPO-ANCA level and found it was positive, but cytoplasmic-ANCA (c-ANCA) was negative. There were no symptoms that indicated other diseases associated with MPO-ANCA. She was confirmed to be at 6 weeks gestation, and thyroid hormone levels were elevated at that time. We discontinued PTU and gave methyl-mercaptoimidazole (MMI), and the titer of MPO-ANCA fell along with fever. Therefore we estimated the case as probable MPO-ANCA positive vasculitis induced by PTU. MMI was also suspended because of the development of hepatic dysfunction. After thyroid function was normalized by administration of potassium iodide, she underwent subtotal thyroidectomy, and delivered a 2350 g infant at 38 weeks' gestation, which was less than the normal birth weight of 2400 g. MPO-ANCA is considered to be one reason of low birth weight infant including hyperthyroidism. It is necessary to consider the appearance of the possibility of MPO-ANCA positive vasculitis in patients who are treated with PTU.     

False positive antineutrophil cytoplasmic antibody in a patient with infective endocarditis

We report a gentleman suffering from purpuric skin rash mimicking vasculitis associated with impaired renal function. He was found to have positive cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) in the serum, but the test for anti-proteinase 3 antibodies (PR3-ANCA) was negative. Blood culture and echocardiogram confirmed the diagnosis of Streptococcal Oralis infective endocarditis. The renal biopsy did not show any features of vasculitis or crescentic glomerulonephritis. His skin rash subsided and renal function normalized after treatment of the infective endocarditis with appropriate antibiotics. Therefore, we conclude that for those patients presenting with features of vasculitis and a positive ANCA test, other causes, such as infective endocarditis, should be considered.     

DRESS syndrome associated with HHV-6 reactivation

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious condition associated with drugs. We report the case of a patient with a febrile skin eruption associated with eosinophilia and hepatitis following drug intake. Serological testing for human herpes virus 6 (HHV-6) was positive. Skin biopsy was compatible with DRESS syndrome. Despite discontinuation of all medications and initiating of corticosteroids, the patient developed acute renal and cardiac failure leading to death. Diagnosis, pathophysiology, and treatment are discussed.     

A Case of HIV Infection with Thrombocytopenia: Assosiation of HIV,Thrombotic Thrombocytopenic Purpura and Brucellosis

To report a case of HIV infection presenting with thrombotic thrombocytopenic purpura (TTP) and brucellosis that responded well to plasmapheresis and anti-infective therapy. A 64-year-old woman with moderate confusion, fever and pancytopenia was admitted. HIV infection history was taken from her family and she was not receiving antiretroviral therapy last one year. She had generalized purpuric skin lesions. Wright tube agglutination test was found positive with a 1:160 dilution and the patient was diagnosed as brucellosis. Detailed literature search showed brucellosis as a possible cause of TTP. Patient was treated by plasma exchange/fresh frozen plasma and antimicrobials and the response was excellent. Although brucellosis seems to explain the clinical picture of this patient, it is revealed that broad differential diagnosis is needed to reach uncommon diagnosis like TTP particularly in HIV infected patients.     

Isolated Severe Immune Thrombocytopenia due to Acute Brucellosis

Mild anemia and leukopenia are the most common hematologic findings in the course of acute brucellosis. However severe form of thrombocytopenia is less frequently reported. The patient was admitted to the hospital with fever, gingival bleeding, and petechial skin lesions related to severe thrombocytopenia. He was investigated for the causes of thrombocytopenia. Test results showed that Wright agglutination test was positive at 1/5120 titer, and blood culture was positive for Brucella melitensis. Finally, he was diagnosed as acute brucellosis. Rifampicin and doxycycline treatment was started on he third day of admission. A bone marrow aspiration was performed on the seventh day of admission because of severe thrombocytopenia did not response to brucellosis treatment. The result of bone marrow aspiration was consistent with idiopathic thrombocytopenic purpura. With the addition of corticosteroid treatment, his complaints resolved immediately, and thrombocyte count rose to normal range. He was discharged on the 12th day of rifampicin and doxycycline therapy, and he was successfully completed 6-week therapy. In cases of brucella induced immune thrombocytopenia, corticosteroid treatment might be useful for the prevention of bleeding complications.     

Drug neosensitization during anticonvulsant hypersensitivity syndrome.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, severe drug hypersensitivity reaction included in the drug-related rash with eosinophilia and systemic symptoms syndrome (DRESS), in which a transient state of immune suppression and reactivation of latent virus infections have been observed. We describe 5 patients who developed neosensitization to different drugs taken during a previous episode of anticonvulsant-related DRESS, in whom skin prick, intradermal and/or patch tests were performed to confirm the diagnosis of drug hypersensitivity. In 1 patient, transient hypogammaglobulinemia was observed during the AHS. Four of the 5 patients developed a delayed skin eruption or a delayed systemic hypersensitivity reaction after intake of a drug that they had also taken during a previous anticonvulsant DRESS which had occurred months or years earlier; in the fifth, a possible reaction was prevented thanks to the allergy workup. The diagnosis of drug allergy was demonstrated by positive delayed reaction to intradermal test with amoxicillin in 2 cases, positive patch tests to paracetamol and amitriptyline in 2 cases, and by clinical evidence of ceftriaxone erythroderma in one. The possibility of neosensitization to drugs administered during anticonvulsant-related DRESS should be considered. A transient state of immunosuppression induced during the anticonvulsant-related DRESS may trigger latent virus reactivation and massive nonspecific immune system response, which may lead to breakdown of tolerance to other drugs present at that time in the organism.     

Anticonvulsant drug hypersensitivity.

BACKGROUND: Cutaneous adverse reactions are frequently described with anticonvulsant drugs, especially with aromatic drugs such as carbamazepine, phenytoin, and phenobarbital. Patch tests could be useful for diagnosing this clinical picture. Hypersensitivity to several anticonvulsant drugs is common but unpredictable. MATERIAL AND METHODS: 15 patients from our allergy section, suffering from anticonvulsant skin allergy, were included. We describe their analitic alterations, responsible drugs, and anticonvulsants tolerated, the results of patch tests with anticonvulsant drugs (5% pet. and aq.), and skin biopsies wherever carried out. RESULTS: 23 adverse skin reactions with different anticonvulsant drugs occurred in the 15 patients: 13 resulted in fever and generalized cutaneous rash, 7 patients suffered only from cutaneous rash. There was one case of palpable purpura, one of erythema multiforme (target lesions), and another one suffered only cutaneous pruritus. Eosinophilia was found in 5 cases. Liver enzymes were elevated in 9 (7 of whom suffered fever and cutaneous rash). The responsible drugs were carbamazepine (8 adverse reactions), phenytoin (5), lamotrigine (4), phenobarbital (4), sodium valproate (1), and felbamate (1). The drugs tolerated were sodium valproate (6 patients), topiramate (4), vigabatrin (2), lamotrigine (1), clonazepam (1), and gabapentin (1). We found 12 positive patch tests: 6 with carbamazepine, 3 with phenytoin and, 1 each with lamotrigine, sodium valproate and phenobarbital. Skin biopsies were carried out in 5 patients, 4 of whom showed some characteristic findings of erythema multiforme (lymphocytic exocytosis, dyskeratotic cells, vacuolation of basal cells and pigmentary incontinence) and the other one showed a typical leucocytoclastic angitis. CONCLUSIONS: The cutaneous adverse reactions more frequently seen in our allergy section because of anticonvulsant drugs are rashes with fever. Eosinophilia and elevated levels of liver enzymes are frequently associated. This clinical picture is called "anticonvulsant hypersensitivity syndrome." The drugs implicated most frequently are carbamazepine and phenytoin. Hypersensitivity to more than one drug was variable and unpredictable. The best-tolerated drug was sodium valproate, but it was not tolerated by a patient with phenytoin and carbamazepine hypersensitivity. Patch tests are useful for diagnosing anticonvulsant hypersensitivity. The most frequently findings in the skin biopsies were typical of erythema multiforme.     

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome: suspected association with titanium bioprosthesis

Drug rash with eosinophilia and systemic symptoms (DRESS), also known as hypersensitivity syndrome, is an idiosyncratic drug reaction presenting with fever, diffuse lymphadenopathy, exfoliative dermatitis, and visceral involvement, which may include hepatitis, pneumonitis, pericarditis, myocarditis, nephritis, and colitis. This report describes a 19-year-old, previously healthy man with manifestations of hypersensitivity (DRESS) syndrome after acquiring a titanium bioprosthesis for a spinal fracture. To our knowledge, there have been no prior reports of DRESS syndrome in association with titanium bioprosthetic implants.     

UNALTERED STIMULATION OF PITUITARY ADRENOCORTICOTROPHIN SECRETION BY CORTICOTROPHIN-RELEASING FACTOR FOLLOWING SODIUM VALPROATE ADMINISTRATION IN A PATIENT WITH NELSON''S SYNDROME

A 53-year-old woman with Nelson's syndrome was treated with 600 mg sodium valproate daily. Her plasma ACTH was effectively decreased, whilst the response of plasma ACTH to corticotrophin-releasing factor (CRF) was unaltered. The result of the CRF test suggested that sodium valproate, at least in the present patient, acted at the hypothalamic level.     

Size reduction of an ACTH-secreting pituitary macroadenoma in Nelson's syndrome by sodium valproate: effect of withdrawal and re-institution of treatment

We describe herein the reduction in the size of an ACTH-secreting pituitary macroadenoma in a patient with Nelson's syndrome during chronic administration of sodium valproate, and the changes in tumour volume after withdrawal and re-institution of treatment. The patient had elevated plasma ACTH levels (1123-1255 pmol/l), which increased markedly after CRH stimulation. A first 4-month course of sodium valproate administration (600 mg/day, orally) was started. Plasma ACTH fell to 550-726 pmol/l with persistence of responsiveness to CRH; brain computed tomography showed a clearcut reduction of tumour size. One month after drug withdrawal, the tumour volume appeared unchanged and plasma ACTH values ranged between 374 and 440 pmol/l. One and a half year after drug withdrawal, a brain computed tomography showed re-expansion of the pituitary adenoma with evidence of suprasellar extension, which had never been seen previously. Plasma ACTH ranged between 113 and 199 pmol/l. A second course of sodium valproate was started; after three months, a brain computed tomography documented clearcut reduction of tumour volume from a suprasellar extension to a partially empty pituitary fossa. Plasma ACTH ranged from 396 to 542 pmol/l with persistence of responsiveness to CRH. The present report documents for the first time the reduction of tumour size in a patient with an ACTH-secreting macroadenoma by chronic administration of sodium valproate.