|
Diagnosed
condition and patient characteristics | Preexisting medical conditions and previous drug exposure | Characteristics of HSR | HHV-6 reactivation characteristics | Status of other bacteria and viral reactivation | Treatment and symptoms resolution | Ref. no. |
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Carbamazepine DIHS
14-year-old
Japanese male | Sodium valproate (600 mg/day) and carbamazepine (200 mg/day) for epilepsy Cefaclor (600 mg/day) for suspected bacterial infection | Fever after 17 days of carbamazepine Facial and body angioedema, generalized lymphadenopathy, mild hepatosplenomegaly, generalized erythema without erosion 11 days after first episode of fever WBC count 31.7 × 109/L (eosinophils 11%, atypical lymphocytes 12.5%), RBC count 4.46 × 1012/L, hemoglobin 13.6 g/dL, platelet count 169 × 109/L, C-reactive protein 1.8 mg/dL, total protein 5.2 g/dL, albumin 3.1 g/dL, AST 137 IU/L, ALT 202 IU/L, LDH 714 IU/L, blood urea nitrogen 10 mg/dL, and creatinine 0.69 mg/dL Transient hypogammaglobulinemia (IgG 649 mg/dL upon admission and 1169 mg/dL on day 26, similar trends for IgM and IgA) | Anti-HHV-6 IgG titers increased from 1 : 10 upon admission to 1 : 10240 23 days later Anti-HHV-6 IgM titers unchanged HHV-6 DNA copy numbers decreased from 3.5 × 1012 copies/106 PBMCs on day 3 to 6.3 × 103 copies/106 PBMCs on day 46 | Anti-HHV-7 IgG titers increased from 1 : 80 to 1 : 160 No changes in HHV-7 DNA copy numbers CMV, EBV, HSV, VZV, or parvovirus B19 serology negative | IV methylprednisolone (30 mg/kg) pulse therapy, followed by oral prednisolone (30 mg/day) | [35] |
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Carbamazepine DIHS
24-year-old
Caucasian female | Carbamazepine (200 mg/day) for oligosymptomatic partial-complex seizures | Fever (38.6°C) with generalized lymphadenopathy and a maculopapular exanthema of the trunk and the perioral region after 6 weeks of carbamazepine WBC count 9.1 × 109/L (19.7% atypical lymphocytes and 8.1% eosinophils) and elevated ALT (50 IU/L) γ-GTP (160 IU/L) and alkaline phosphatase (114 IU/L) | Anti-HHV-6 IgM titers positive Anti-HHV-6 IgG titers increased from 1 : 320 to 1 : 1280 within 25 days of hospitalization HHV-6 DNA detected in serum | EBV, CMV, HBC, HCV, HIV, Toxoplasma gondii or Borrelia burgdorferi serology negative | n/a
Symptoms resolved spontaneously | [36] |
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Carbamazepine DIHS
24-year-old
Japanese female | Carbamazepine for 32 days for agitation and emotional instability Cefcapene pivoxil hydrochloride administered for supposed cervical lymphadenitis | Low-grade fever and cervical lymph node swelling within 2 weeks of carbamazepine
Pleomorphic erythema of the trunk and lower extremities within another week
Fever (39.0°C–39.9°C) and dark purplish pleomorphic erythema over the trunk and extremities within next 10 days
WBC count 14.3 × 109/L (14.8% eosinophils), with severe liver dysfunction characterized by elevated AST (262 IU/L), ALT (423 IU/L), and LDH (827 IU/L) after 32 days of carbamazepine Inguinal lymph node swelling developed and edema in the lower limbs and face progressed Hepatic function worsened | Anti-HHV-6 IgG titer 1 : 80 and the IgM titer <1 : 10 at time of carbamazepine discontinuation Anti-HHV-6 IgG titers increased to 1 : 2560 and IgM titers became positive at 1 : 10 | EBV, CMV, parvovirus B19 and antirubeola virus within normal ranges EBV and CMV serology negative | Not discussed | [37] |
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Carbamazepine DIHS
43-year-old
Japanese female | Haloperidol, paroxetine hydrochloride, levomepromazine, amobarbital, bromovalerylurea chlorpromazine, and carbamazepine for anxiety and confusion | Generalized exudative erythema and fever (39.2°C) after 14 days of carbamazepine Increased WBC count, particularly atypical lymphocyte count Leukocytosis (27.5 × 109/L) with atypical lymphocytosis (36%, 9.9 × 109/L) and eosinophilia (4.5%, 0.88 × 109/L)
Hepatic dysfunction with elevated AST (78 IU/L), ALT (106 IU/L), LDH (873 IU/L), and γ-GTP (556 IU/L) Transient hypogammaglobulinemia | Anti-HHV-6 IgG titers increased from 1 : 10 on day 6 to 1 : 5120 on day 11 Anti-HHV-7 IgG titers increased from 1 : 80 to 1 : 160 HHV-6 DNA detected on day 9, but not on day 11 | EBV, CMV, HSV, VZV and parvovirus B19 serology negative | IV methylprednisolone (1000 mg/day) pulse therapy for 3 days, followed by oral prednisolone (60 mg/day) | [38] |
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Carbamazepine DIHS
54-year-old Turkish female | Carbamazepine for epilepsy | Fever after 20 days of carbamazepine Maculopapular rash, erythroderma, exfoliative dermatitis, fever, facial, and genital edema, lymphadenopathy, hypereosinophilia, hypogammaglobulinemia, atypical lymphocytosis, leukocytosis and abnormal liver function tests | Anti-HHV-6 IgG 1 : 60 on day 7 and 1 : 1920 on day 14
HHV-6 DNA detected by PCR on day 14 | Not specified | Systemic steroids, IV immunoglobulin for 30 days | [39] |
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Carbamazepine DIHS
17-year-old Turkish male | Carbamazepine for brain surgery | Fever after 12 days of carbamazepine Maculopapular rash, erythroderma, bullous lesion, hypereosinophilia, anemia, atypical lymphocytosis, abnormal liver function tests | Anti-HHV-6 IgG 1 : 80 on day 7 and 1 : 2560 on day 14
HHV-6 DNA detected by PCR on day 14 | Not specified | Systemic steroids for 21 days | [39] |
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Carbamazepine DIHS
23-year-old Turkish female | Carbamazepine for epilepsy | Fever after 24 days of carbamazepine Erythroderma, exfoliative dermatitis, vasculitis (purpura), genital ulcer, lymphadenopathy, leukocytosis, hypereosinophilia, atypical lymphocytosis, abnormal liver function tests | Anti-HHV-6 IgG 1 : 20 on day 7 and 1 : 1280 on day 14
HHV-6 DNA not specified detected by PCR on day 14 | Not specified | Systemic steroids for 30 days | [39] |
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Carbamazepine DIHS
29-year-old Turkish male | Carbamazepine for brain surgery | Fever after 22 days of carbamazepine Maculopapular rash, vasculitis (purpura), facial and genital edema, hypereosinophilia, leukocytosis, abnormal liver function tests, splenomegaly | Anti-HHV-6 IgG 1 : 20 on day 7 and 1 : 1280 on day 14
HHV-6 DNA detected by PCR on day 14 | Not specified | Systemic steroids for 20 days | [39] |
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Carbamazepine DIHS
15-year-old Turkish female | Carbamazepine for epilepsy | Fever after 20 days of carbamazepine Erythroderma, lymphadenopathy, leukocytosis, hypereosinophilia, atypical lymphocytosis, increased in serum amylase (pancreatitis), abnormal liver function tests, lung pneumonia | Anti-HHV-6 IgG 1 : 30 on day 7 and 1 : 1920 on day 14
HHV-6 DNA detected by PCR on day 14 | Not specified | Systemic steroids for 18 days | [39] |
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Carbamazepine DIHS accompanied by dermatologic changes and
HHV-6 reactivation 14-year-old
Japanese male | Carbamazepine (200 mg/day) for localization-related epilepsy | Fever (37.8°C) after 3 weeks of carbamazepine Liver dysfunction with AST 403 IU/L, ALT 549 IU/L and LDH 637 IU/L upon admission Erythroderma with edematous changes spread over the entire body WBC count 34.5 × 109/L, with 19.5% atypical lymphocytes and 23.5% eosinophils prior to day 11 Liver dysfunction worsened with AST 1170 IU/L and ALT 700 IU/L on day 15 No cervical, axial, or inguinal lymphadenopathy detected | HHV-6 DNA (32000 copies/μg of DNA) detected by real-time PCR and anti-HHV-6 antibodies isolated from PBMCs on day 19 Anti-HHV-6 IgG increased 5120-fold on day 25 | HAV, HBV, CMV, EBV serology negative | Corticosteroids (1 mg/kg/day) | [40] |
|
Carbamazepine DIHS possibly triggered by
HHV-6 reactivation 12-year-old Italian female | Amoxicillin Sodium valproate for generalized epileptic seizure, replaced with carbamazepine | Fever (>39°C), cutaneous rash with mild face edema and moderate laterocervical lymphadenopathy after 5 weeks of carbamazepine Normal hemochrome with moderate lymphopenia (0.8 × 109/L) and increased AST (200 IU/L), ALT (181 IU/L), and γ-GTP (116 IU/L) | Anti-HHV-6 IgG titers >1 : 128 HHV-6 and HHV-7 DNA detected | EBV, CMV, toxoplasma, Bartonella serologies, influenza, adenovirus, and respiratory syncytial virus serology negative | IV methylprednisolone (1 mg/kg) for 3 days, followed by oral methylprednisolone | [41] |
|
Carbamazepine DIHS
48-year-old
Japanese male | Carbamazepine (400 mg/day) for a psychiatric disease | High-grade fever and erythematous rash on his trunk after 43 days of carbamazepine Leukocytosis (9.3 × 109/L (0% eosinophilia/13% atypical lymphocytosis)) Lymphadenopathy Severe liver dysfunction with highest ALT level 1859 IU/L
Worsening of rash and liver dysfunction at time of EBV reactivation Thyroid dysfunction at time of HHV-6 and HHV-7 reactivation | Increase in HHV-6 viral load Dramatic increase in anti-HHV-6 IgG titers | Increase in EBV viral load after 9 days of hospitalization HHV-7 reactivation | None | [42] |
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Phenobarbital
DIHS
68-year-old
Japanese male | Phenobarbital (120 mg/day) for epileptic fits | Erythematous rash on chest and trunk, fever and malaise after 43 days of phenobarbital Leukocytosis (17.4 × 109/L (6% eosinophilia/1% atypical lymphocytosis)) Lymphadenopathy Liver dysfunction with highest ALT level 323 IU/L Neurological symptoms developed in conjunction with increased HHV-6 viral load Neurological symptoms reappeared with rise in HHV-7 viral load | HHV-6 DNA detected 19 days after hospitalization Dramatic rise in anti-HHV-6 IgG titers but not IgM titers | EBV viral load increased as HHV-6 decreased HHV-7 viral load increased within a few months of HHV-6 CMV viral load increased with no clinical symptoms | Prednisolone (60 mg/day) | [42] |
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Salazosulfapyridine DIHS
68-year-old
Japanese male | Salazosulfapyridine (2000 mg/day) for rheumatoid arthritis Previous exposure to prednisolone | High-grade fever, malaise, and rash extending to trunk and lower extremities after 28 days of salazosulfapyridine Leukocytosis (17.7 × 109/L (0% eosinophilia/2% atypical lymphocytosis)) Facial edema, lymphadenopathy and leucopenia upon admission Slight liver dysfunction with highest ALT level 44 IU/L Herpes labialis with herpetic stomatitis at time of HSV reactivation 13 days after admission Erythematous rash with transient high fever and dry cough developed at time of CMV antigens detection | HHV-6 DNA detected in blood upon admission Dramatic rise in anti-HHV-6 IgG titers | HSV reactivation HSV antigens EBV and CMV DNA detected | Prednisolone (40 mg/day) | [42] |
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Mexiletine
DIHS
74-year-old
Japanese male | Mexiletine for arrhythmia | High-grade fever and generalized erythematous rash on the chest and trunk after 31 days of mexiletine Leukocytosis (9.2 × 109/L (14% eosinophilia/2% atypical lymphocytosis)) Lymphadenopathy Liver dysfunction with highest ALT level 156 IU/L Cytomegalovirus antigenemia and massive internal bleeding following detection of CMV DNA Slight liver dysfunction following detection of EBV DNA | HHV-6 DNA detected Increased anti-HHV-6 IgG titers | Increased EBV and CMV viral loads | Prednisolone (50 mg/day) Ganciclovir (200 mg/day) | [42] |
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Anticonvulsant DIHS with HHV-6 reactivation developed after initial exanthema subitum
complicated with febrile seizure 11-month-old
Japanese female | IV diazepam for right tonic hemiconvulsions and upward deviation of the eyes Oral carbamazepine initiated in place of thiopental 10 days after hospitalization Carbamazepine replaced with phenobarbital IV phenytoin added on day 14 and continued for 11 days | Fever (39.1°C) without skin symptoms after 14 days of phenobarbital Erythematous rash appeared and spread over the entire body after 4 additional days Maculopapular erythematous rash appeared on face, extremities, and trunk after carbamazepine exposure Cervical lymphadenopathy Facial edema after phenobarbital discontinuation Elevated eosinophil count (1.9 × 109/L), AST (105 IU/L) and ALT (45 IU/L) | HHV-6 DNA first detected on day 5 (635 copies/mL in serum and 31.5 copies/mL in cerebrospinal fluid), coinciding with the eruptive stage of exanthema subitum HHV-6 DNA undetectable on day 16 HHV-6 DNA detected on day 28 (805 copies/mL in serum), coinciding with high fever and generalized erythema HHV-6 DNA increased on day 30 (4360 copies/mL in serum) when DIHS was suspected Anti-HHV-6 IgG titers negative upon admission Anti-HHV-6 IgG titers elevated on day 11 (256-fold) and day 34 (128-fold) | Not specified | Continuous infusion of thiopental and assisted mechanical ventilation, as well as IV methylprednisolone pulse therapy (30 m/kg/day for 3 days), γ-globulin, and acyclovir therapy for initial condition IV methylprednisolone for resolution of DIHS | [43] |
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Phenobarbital
DIHS and fulminant hemophagocytic syndrome associated with HHV-6 reactivation
25-year-old
Laotian female | Oral phenobarbital for epileptic seizures | Fever (40°C), diffuse pruritic exfoliative dermatitis with edema of the face and purpuric lesions on the extremities, enlarged cervical, axillary and inguinal lymph nodes, and hepatomegaly after 18 days of phenobarbital Atypical lymphocytes with leukocytosis (24.5 × 109/L), eosinophilia (5.14 × 109/L), and lymphocytosis (7.1 × 109/L) with predominant T phenotype (90% CD3, 1% CD19) Liver dysfunction with elevated ALT (465 IU/L), AST (165 IU/L), and LDH (19000 U/mL) Severe erythroderma complicated by methicillin-resistant Staphylococcus aureus septicemia on day 13 Acute hepatic failure with ALT 1415 IU/L and AST 2525 IU/L | Anti-HHV-6 IgG titers 1 : 80 on day 14 and >1 : 320 on day 29 HHV-6 DNA not detected in serum by PCR | EBV, CMV, HIV, human T-cell lymphotropic virus type 1, parvovirus B19, HCV, HBV, picornavirus, Toxoplasma gondii and Treponema pallidum serology negative | Oral corticosteroids and etoposide Corticosteroid therapy continued >1 year
IV vancomycin (2 g/day) | [44] |
|
Phenobarbital
DIHS with
multiple viral reactivations
43-year-old
Japanese male | Phenobarbital (300 mg daily) for a brain aneurysm | High-grade fever, bilateral cervical and inguinal lymphadenopathy, and hepatomegaly after 44 days of phenobarbital Blood cell count 11.8 × 109/L, with eosinophil count 3.08 × 109/L Liver dysfunction with elevated AST 273 IU/L, ALT 770 IU/L, LDH 582 IU/L and C-reactive protein 12.7 mg/dL
Hypogammaglobulinemia with serum IgG levels 769 mg/dL, IgA levels 47 mg/d/L and IgM levels 76 mg/dL Skin biopsy revealed dense infiltration consisting mainly of mononuclear cells and eosinophils in the upper dermis | Dramatic increases in anti-HHV-6 IgG on day 19 | Dramatic increases in anti-CMV IgM on day 19 Increase in anti-HHV-7 IgG EBV serology negative | Initial HSR symptoms resolved spontaneously Treatment not administered | [45] |
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Phenobarbital DIHS 31-year-old
Japanese female | Phenobarbital for depression | Fever, severe systemic erythematous eruptions followed by systemic lymphadenopathy and hepatosplenomegaly after 3 weeks of phenobarbital WBC count 105.4 × 109/L, with 25% eosinophils and 52% atypical lymphocytes, platelet count 161 × 109/L and hemoglobin concentration 9.4 g/dL Liver dysfunction with AST 70 IU/L, ALT 93 IU/L, alkaline phosphatase 824 IU/L, γ-GTP 592 IU/L, and LDH 364 IU/L | Anti-HHV-6 IgG 1 : 2560 and IgM 1 : 40
HHV-6 DNA 6.3 × 103 copies/mL in PBMCs | EBV, CMV, VZV, and HSV serology negative | Methylprednisolone (1000 mg/day) for 3 days, followed by prednisolone (60 mg/day) | [46] |
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Aromatic anticonvulsants DIHS developed concomitantly to HHV-6 seroconversion
in 56-year-old
Japanese male | Hypertension Sodium valproate (600 mg/day) for a 6-month history of generalized convulsion of unknown cause Phenytoin (134 mg/day) and phenobarbital (66 mg/day) for 3 weeks Acyclovir (20 mg/kg/day) for was believed to be HSV encephalitis | Generalized erythematous macules after 3 weeks of phenytoin and phenobarbital High-grade fever (39.8°C), generalized erythroderma and edema within 1 week WBC count 23.3 × 109/L (23% eosinophils and 9.5% atypical lymphocytes) Abnormal liver function Skin biopsy revealed a spongiotic epidermis with liquefactive degeneration of the epidermal basal layer Encephalopathy of nonmetabolic origins
Death with multiple organ failure 18 days after falling into a coma and 5 weeks after rash appearance | Anti-HHV-6 IgG titers increased from 1 : 80 one month after appearance of macular rash to 1 : 640 within next 2 weeks Anti-HHV-6 IgM negative | HSV-1, HSV-2, VZV, CMV, EBV, measles, rubella, and mumps serology positive | Oral prednisone (30 mg/day) IV diazepam for frequent partial seizures developed during hospital stay | [47] |
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Anticonvulsant DIHS
6-year-old Tunisian child | Sodium valproate (600 mg/day) intermittently for 41 days Ethosuximide (500 mg/day) intermittently for 29 days for epileptic absences Ethosuximide interrupted prior to the hospitalization | High-fever (40°C), facial edema, diffuse pruritic morbilliform skin eruption with vesicular, and target lesions after 41 days of intermittent sodium valproate
Leukocytosis of 17.9 × 109/L, eosinophilia of 2.0 × 109/L, lymphocytosis of 8.95 × 109/L and monocytosis of 1.43 × 109/L, with normal platelet count Elevated C-reactive protein (57 mg/mL), AST (70 IU/L), γ-GTP (50 IU/L), and LDH (1020 IU/L) Histologic analysis revealed a spongiotic epidermis with necrotic keratinocytes and a lymphocytic perivascular dermal infiltrate with a few hyperchromatic lymphocytes with irregular nuclei | Anti-HHV-6 IgG titers increased from 1 : 40 to 1 : 120 in the course of 120 days | EBV, HIV, HAV, HBV, HCV, CMV, parvovirus B19, herpes simplex virus and Mycoplasma pneumoniae serology negative | Oral prednisone (1 mg/kg/day) | [48] |
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Zonisamide DIHS 29-year-old
Japanese male | Zonisamide (300 mg/day) for temporal epilepsy, interrupted 7 days prior to admission Cefcapene pivoxil hydrochloride hydrate, acetaminophen, tranexamic acid, and lansoprazole prescribed 7 days prior to admission | Acute kidney injury and diffuse skin rash with edema of the face after 2 months of zonisamide Fever, elevated AST (65 IU/L), ALT (132 IU/L), and γ-GTP (153 IU/L) levels 4 days prior to admission Facial edema and a generalized pruritic maculopapular rash with lichen upon admission Lymphadenopathy, eosinophilia, renal dysfunction, liver dysfunction, and hypogammaglobulinemia Splenomegaly and enlarged kidneys with serum creatinine level of 8.20 mg/dL Fever persisted and eruptions evolved to flaccid vesicles and bullae 4 days after admission Skin biopsy revealed multiple epidermal bullous formation with eosinophilic abscess
Renal biopsy performed revealed glomeruli with minor abnormality, with infiltration of mononuclear cells and eosinophilic cells around each glomerulus and focal interstitium and interstitial edema with swelling and degeneration of tubular epithelial cells | HHV-6 DNA detected by PCR on day 6 but not on day 20 Anti-HHV-6 IgG levels increased from 1 : 16 on day 2 to 1 : 256 on day 27 | Not specified | Hemodialysis Prednisolone (60 mg/day) started 4 days after admission | [49] |
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Lamotrigine
DIHS
26 year-old Italian female | Additive mastoplasty for von Willembrandt disease in childhood Current escitalopram and lamotrigine for a bipolar disease Cefixime (400 mg twice/day) for 3 days, betamethasone, 1 mg and fexofenadine 120 mg for 1 day, and azithromycin 500 mg once/day for 3 days for fever (≤39.5°C) developed 16 days prior to admittance | Fever after 30 days of lamotrigine
Asthenia, nausea, myalgia, and arthralgia, as well as a maculopapular rash on the face, neck, trunk and superior and inferior limbs, hard and tender lymph nodes, and hepatomegaly upon admission Lymphadenopathy Eosinophilic leukocytosis (31.7 × 109/L, with 18% eosinophils)
Increases in CD4 (3.7 × 109/L) and CD8 (5.8 × 109/L) T lymphocyte counts Severe liver dysfunction with 19-fold increased ALT and 14-fold increased AST High bilirubin level (2.84 mg/dL) and low prothrombin activity (39%) | Anti-HHV-6 IgG and IgM detected on day 11
HHV-6 DNA 8590 copies/mL in blood with real-time PCR | HAV, HBV, HCV, EBV, CMV, rubella, adenovirus, coxsackievirus, influenza virus A/B, parainfluenza virus serology negative Antibodies against Borrelia burgdorferi, Rickettsia conori, Rickettsia typhi, Chlamydia trachomatis, and Leishmania infantum negative | IV betamethasone (8 mg 3 times/day) and IV acyclovir (250 mg 3 times/day) for 8 days
Fresh frozen plasma infusions, physiological solutions, and proton pomp inhibitors Prednisone (50 mg/day) | [50] |
|
Lamotrigine
DRESS
75-year-old
French male | Lamotrigine (25 mg/day) for generalized tonic-clonic seizures | Diffuse exanthematous maculopapular rash affecting between 50% and 70% of the skin surface, fever, peripheral lymphadenopathies, and abdominal pain after 40 days of lamotrigine Hyperleukocytosis with hypereosinophilia Skin biopsy showed marked infiltration of the dermo-epidermal junction with lymphocytes and keratocyte necrosis Acute edematous pancreatitis diagnosed based on increased pancreas size Bilateral basal crackles on lung auscultation and hepatomegaly, as well as severe acute cytolytic and cholestatic hepatitis with hepatocellular insufficiency Oliguria and kidney failure Multiorgan failure by day 55 | Positive anti-HHV-6 IgM serology HHV-6 DNA 11000 copies/mL | HIV, HAV, HBV, HCV, EBV, HSV-1 HSV-2, CMV serology negative | Prednisone (1 mg/kg/day) for 20 days | [51] |
|
Carbamazepine DIHS
59-year-old
Japanese male | Carbamazepine | Fever (>38.5°C) after 30 days of carbamazepine Liver dysfunction with ALT 119 IU/L and γ-GTP 79 IU/L
WBC count 16.2 × 109/L and eosinophils count 0.45 × 109/L (16% atypical lymphocytes) Lymph node enlargement | Anti-HHV-6 IgG titers 1 : 160 during active phase and 1 : 1280 during recovery phase | Not specified | Prednisolone (40 mg/day) | [52] |
|
Carbamazepine DIHS
56-year-old
Japanese female | Carbamazepine | Fever (>38.5°C) after 22 days of carbamazepine Severe liver dysfunction with ALT 706 IU/L and γ-GTP 318 IU/L WBC count 11.5 × 109/L and eosinophils count 0.83 × 109/L (15% atypical lymphocytes) Lymph node enlargement | Anti-HHV-6 IgG titers 1 : 160 during active phase and 1 : 160 during recovery phase | Not specified | Prednisolone (40 mg/day) | [52] |
|
Carbamazepine DIHS
62-year-old
Japanese female | Carbamazepine | Fever (>38.5°C) after 51 days of carbamazepine No liver dysfunction with ALT 9 IU/L and γ-GTP 40 IU/L
WBC count 7.8 × 109/L and eosinophils count 1.2 × 109/L (8% atypical lymphocytes) Lymph node enlargement | Anti-HHV-6 IgG titers 1 : 10 during active phase and 1 : 640 during recovery phase | Not specified | Betamethasone (2 mg/day) | [52] |
|
Carbamazepine DIHS
53-year-old
Japanese female | Carbamazepine | Fever (>38.5°C) after 26 days of carbamazepine Liver dysfunction with ALT 327 IU/L and γ-GTP 108 IU/L WBC count 6.4 × 109/L and eosinophils count 0.39 × 109/L
Lymph node enlargement | Anti-HHV-6 IgG titers 1 : 640 during active phase and 1 : 10240 during recovery phase | Not specified | Corticosteroids not used | [52] |
|
Carbamazepine DIHS
71-year-old
Japanese male | Carbamazepine | Fever (>38.5°C) after 50 days of carbamazepine Liver dysfunction with ALT 108 IU/L and γ-GTP 140 IU/L
WBC count 8.1 × 109/L and eosinophils count 0.50 × 109/L
Lymph node enlargement | Anti-HHV-6 IgG titers 1 : 10 during active phase and 1 : 160 during recovery phase | Not specified | Prednisolone (30 mg/day) | [52] |
|
Zonisamide DIHS 27-year-old
Japanese female | Zonisamide | Fever (>38.5°C) after 26 days of zonisamide Severe liver dysfunction with ALT 401 IU/L and γ-GTP 220 IU/L
WBC count 21.3 × 109/L and eosinophils count 0.66 × 109/L (49% atypical lymphocytes)
Lymph node enlargement | Anti-HHV-6 IgG titers 1 : 40 during active phase and 1 : 1280 during recovery phase | Not specified | Prednisolone (30 mg/day) | [52] |
|
Phenobarbital SJS
72-year-old
Japanese female | Phenobarbital | Fever (>38.5°C) after 31 days of phenobarbital Mild liver dysfunction with ALT 72 IU/L and γ-GTP 28 IU/L
WBC count 15.8 × 109/L and eosinophils count 0.42 × 109/L
5% detachment of the total body surface area | Anti-HHV-6 IgG titers 1 : 40 during active phase and 1 : 20 during recovery phase | Not specified | Prednisolone (40 mg/day) | [52] |
|
Phenytoin SJS
19-year-old
Japanese female | Phenytoin | Fever (>38.5°C) after 26 days of phenytoin Liver dysfunction with ALT 90 IU/L and γ-GTP 436 IU/L
WBC count 12.8 × 109/L and eosinophils count 0.90 × 109/L Lymph node enlargement 10% detachment of the total body surface area | Anti-HHV-6 IgG titers 1 : 80 during active phase and 1 : 80 during recovery phase | Not specified | Prednisolone (60 mg/day) | [52] |
|
Zonisamide TEN
71-year-old
Japanese male | Zonisamide (300 mg/day) for symptomatic epilepsy History of long-term valproate sodium therapy | Fever (40.2°C) and rash after 23 days of zonisamide Erythematous macules resulting in diffuse areas of erythema with erosions and blisters located on the trunk and upper extremities 40% detachment of the total body surface area, with extensive hemorrhagic erosions on the lips, oral mucosa, pharynx, and larynx Elevated ALT (48 IU/L), LDH (379 IU/L), γ-GTP (111 IU/L), and C-reactive protein (11.3 mg/L) WBC count 12.5 × 109/L and eosinophils count 1.02 × 109/L Skin biopsy revealed prominent eosinophilic necrosis of the keratinocytes and subepidermal blister Moderate inflammatory infiltrate consisting of mononuclear cells in the upper dermis Skin eruptions and high fever returned 9 days after initial onset | Anti-HHV-6 IgG titers 1 : 10 during active phase (day 4) and 1 : 1280 during recovery phase (day 22) HHV-6 DNA levels increased from 2.0 × 101 copies/106 cells on day 4 to 1.3 × 102 copies/106 cells on day 22 in PBMCs | No change in HSV, CMV or EBV IgG titers | IV immunoglobulin therapy (5 g/day) for 3 days resulted in slowing of disease progress | [52] |
|
Zonisamide TEN
66-year-old
Japanese male | Zonisamide | Fever (>38.5°C) after 25 days of zonisamide Mild liver dysfunction with ALT 58 IU/L and γ-GTP 61 IU/L
WBC count 10.1 × 109/L and eosinophils count 0.28 × 109/L
40% detachment of the total body surface area | Anti-HHV-6 IgG titers 1 : 40 during active phase and 1 : 40 during recovery phase | Not specified | Methylprednisolone (500 mg/day), followed by Prednisolone (30 mg/day) | [52] |
|
