Adverse drug reactions can cause considerable discomfort. They can be life-threatening in severe cases, requiring or prolonging hospitalization, impeding proper treatment, and increasing treatment costs considerably. Although the incidence of severe cutaneous adverse reactions (SCARs) is low, they can be serious, have permanent sequelae, or lead to death. A recent pharmacogenomic study confirmed that genetic factors can predispose an individual to SCARs. Genetic markers enable not only elucidation of the pathogenesis of SCARs, but also screening of susceptible subjects. The human leukocyte antigen (HLA) genotypes associated with SCARs include HLA-B*57:01 for abacavir (Caucasians), HLA-B*58:01 for allopurinol (Asians), HLA-B*15:02 (Han Chinese) and HLA-A*31:01 (Europeans and Koreans) for carbamazepine, HLA-B*59:01 for methazolamide (Koreans and Japanese), and HLA-B*13:01 for dapsone (Asians). Therefore, prescreening genetic testing could prevent severe drug hypersensitivity reactions. Large-scale epidemiologic studies are required to demonstrate the usefulness and cost-effectiveness of screening tests because their efficacy is affected by the genetic differences among ethnicities.
Allopurinol ; Carbamazepine ; Cicatrix ; Dapsone ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Epidemiologic Studies ; Genetic Markers* ; Genetic Testing ; Genotype ; Health Care Costs ; HLA Antigens ; Hospitalization ; Humans ; Incidence ; Leukocytes ; Mass Screening ; Methazolamide ; Pharmacogenetics ; Stevens-Johnson Syndrome

BACKGROUND/AIMS: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions that frequently result in fatal outcomes. We investigated cases of SJS and TEN in a regional hospital. METHODS: From 2008 to 2014, SJS and TEN cases were enrolled retrospectively by allergy and dermatology specialists, and their clinical features and severity-of-illness score for TEN (SCORTEN) were assessed. RESULTS: During the 7-year study period, 56 SJS and 14 TEN cases were recruited. The majority (71%) were 40-70 years of age (mean age of male and female patients, 55 and 54 years, respectively). Regarding drugs, anticonvulsants (42.8%) were the most frequently causative, followed by carbonic anhydrase inhibitors (20.0%), antimicrobials (15.7%), allopurinol (7.1%), and non-steroidal anti-inflammatory drugs (7.1%). No fatal case of SJS was seen. However, 7 of the 14 patients with TEN died (50%; mean age, 67 years; 1 of 5 [20%] males and 6 of 9 females [66.7%]). The mortality rate was reflected in the SCORTEN values. Vancomycin, allopurinol, methazolamide (two cases each) and megestrol (one case) were the causative drugs in the seven fatal TEN cases. Treatment modality did not affect the likelihood of death due to TEN. CONCLUSIONS: The causative drugs of, and frequency of mortality due to, SJS and TEN should be recognized by physicians. Elderly females with TEN are at high risk of mortality. SCORTEN values reflect the mortality rate of TEN patients. Early recognition and proper management of SJS and TEN may reduce the mortality rate.
Aged ; Allopurinol ; Anticonvulsants ; Carbonic Anhydrase Inhibitors ; Dermatology ; Drug-Related Side Effects and Adverse Reactions ; Fatal Outcome ; Female ; Humans ; Hypersensitivity ; Male ; Megestrol ; Methazolamide ; Mortality ; Retrospective Studies ; Specialization ; Stevens-Johnson Syndrome* ; Vancomycin

PURPOSE: To report a case involving an unexpected increase in intraocular pressure (IOP) and acute angle closure after oral administration of methazolamide. CASE SUMMARY: A 38-year-old male visited the emergency department complaining of decreased visual acuity (VA) and ocular pain. These symptoms developed after he took two tablets of 50 mg methazolamide because his IOP was above normal after a short course of systemic steroid treatment. His uncorrected VA dropped to 0.04 and the refractive error was −6.5 diopters in both eyes. The anterior chamber was very shallow, and the IOPs were 46 mmHg in the right eye and 42 mmHg in the left eye. Macular retinal folds were observed in both eyes in infrared fundus images. The patient was instructed not to take methazolamide, which was suspected as the cause of this idiosyncratic drug reaction. He was prescribed topical anti-glaucoma medications and cycloplegics to relieve the acute angle closure, and all symptoms disappeared after these treatments. CONCLUSIONS: Methazolamide is a sulfa derivative like topiramate, which can cause acute angle closure involving edema of the ciliary body and anterior displacement of the lens-iris diaphragm. Clinicians should consider this possible IOP increase before prescribing methazolamide.
Administration, Oral ; Adult ; Anterior Chamber ; Ciliary Body ; Diaphragm ; Edema ; Emergency Service, Hospital ; Humans ; Intraocular Pressure* ; Male ; Methazolamide* ; Mydriatics ; Refractive Errors ; Retinaldehyde ; Tablets ; Visual Acuity

Among various dermatological entities, toxic epidermal necrolysis (TEN) is a rare but potentially fatal delayed hypersensitivity reaction to numerous medications. A 38-year-old male presented with systemic hypersensitivity reaction, such as high fever, pain in the eyes, and diffuse pruritic erythematous maculopapular eruptions with multiple targetoid plaques that became vesicular and bullous. Oral mucosa and conjunctivae were involved. The first sign appeared about 1 week after taking methazolamide (50 mg twice a day) for the management of glaucomatous eyes. Although methazolamide was discontinued, blistering and skin denudation progressed to affect up to 80% of the body surface area and a positive Nikolsky sign was noted. High fever also persisted. Skin lesions started to improve after 2 weeks of management and fever subsided. Cutaneous lesions improved with minimal permanent sequele 2 months later. HLA-B*5901 was found by high-resolution genotyping. The lymphocyte activation test performed 6 months after remission showed a positive response to methazolamide challenge. This is the first case of methazolamide-induced TEN in which methazolamide was confirmed as a culprit drug by the lymphocyte activation test.
Adult ; Blister ; Body Surface Area ; Conjunctiva ; Fever ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Lymphocyte Activation* ; Lymphocytes* ; Male ; Methazolamide ; Mouth Mucosa ; Skin ; Stevens-Johnson Syndrome*

Recently, Stevens-Johnson syndrome associated with methazolamide has been reported in Koreans, more frequently. Methazolamide is a carbonic anhydrase inhibitor commonly used for lowering intraocular pressure in glaucoma and other ophthalmologic diseases. We reported five cases of Stevens-Johnson syndrome induced by methazolamide. All patients showed atypical clinical manifestations, compared to classical Stevens-Johnson syndrome. Methazolamide induced Stevens-Johnson syndrome showed scattered or confluent maculopapular eruptions initially, which are similar to morbiliform drug eruption with mild lip erosion and palmar erythema. Even though there was no skin erosion initially, it showed rapid progression to severe erosion on the trunk and palmoplantar erythema within 5 to 7 days. Therefore, our data indicated that methazolamide induced Stevens-Johnson syndrome should be checked for a patient who has a history of ophthalmologic treatment with a drug eruption like skin lesion.
Carbonic Anhydrases ; Drug Eruptions ; Erythema ; Glaucoma ; Humans ; Intraocular Pressure ; Lip ; Methazolamide ; Skin ; Stevens-Johnson Syndrome

A 54-year-old female patient who had been undergoing anti-cancer chemotherapy and radiotherapy for seven years after surgery for left breast cancer visited our clinic for visual disturbance in the right eye at nine months after paclitaxel administration. The best-corrected visual acuity was 0.5 in the right eye and 1.0 in the left eye. The patient was diagnosed with maculopathy due to paclitaxel administration based on the finding of cystoid macular edema in the right eye on fundus examination and optical coherence tomography; however, no leakage was detected on fluorescein angiography. Thus, drug replacement was planned. On the other hand, no abnormal finding was observed in the left eye. However, as the anti-cancer effect of paclitaxel is significant, replacing paclitaxel with another agent was not warranted; therefore, maintenance therapy with methazolamide was performed before and after administering the anti-cancer agent. Aggravation of cystoid macular edema was prevented, and vision improvement was achieved by oral maintenance therapy with methazolamide. In addition, the same fundus findings as shown in the right eye were detected in the left eye at 16 months after paclitaxel administration. After administering methazolamide, macular thickness was reduced, and vision was improved in the left eye. Paclitaxel administration was discontinued due to cutaneous metastasis from the breast cancer, and another anti-cancer agent was then administered. No subsequent cystoid macular edema has occurred.
Antineoplastic Agents, Phytogenic/*adverse effects ; Breast Neoplasms/drug therapy ; Diuretics/*therapeutic use ; Female ; Humans ; Macular Edema/*chemically induced/*drug therapy ; Methazolamide/*therapeutic use ; Middle Aged ; Paclitaxel/*adverse effects ; Visual Acuity

PURPOSE: Acute mountain sickness (AMS) commonly occurs when unacclimatized individuals ascend to altitudes above 2500 m. Acetazolamide, a carbonic anhydrase inhibitor (CAI), is recommended for AMS prophylaxis, but may have adverse effects such as paresthesia. Methazolamide has the same pharmacologic effect, but diffuses more rapidly into tissue and is more potent than acetazolamide. But, little is known about methazolamide as an AMS prophylactic agent. This study was conducted to prospectively compare metazolamide with acetazolamide for its preventive effect for AMS in adolescents. METHODS: Nineteen adolescents aged 13~18 years attempting an ascent of Mt. Kalapatar (5500 m) were randomly divided to receive acetazolamide (n=10) or methazolamide (n=9). Oxygen saturation (SpO2) and pulse rate were measured at each altitude. The incidence of AMS was calculated using the Lake Louise questionnaire. Difference in incidence between two groups was analyzed using generalized estimating equation. Difference in Lake Louise scores (LLS) was analyzed using linear mixed model testing. RESULTS: Overall incidence of AMS was 68.4%. Fatigue or malaise was the most frequent symptom (94.7%) followed by headache (84.2%). SpO2 decreased as the altitude increased (p<0.001). There was no difference in SpO2 and pulse rate between the two groups (p=0.44). There was no difference in LLS (p=0.22) and incidence of AMS (p=0.07) between the two groups with increasing altitude. Paresthesia was less common in the methazolamide group, but was not statistically different (p=0.35). CONCLUSION: Methazolamide is equally effective as acetazolamide in preventing AMS among adolescents.
Acetazolamide ; Adolescent ; Aged ; Altitude ; Altitude Sickness ; Carbonic Anhydrases ; Fatigue ; Headache ; Heart Rate ; Humans ; Incidence ; Lakes ; Methazolamide ; Oxygen ; Paresthesia ; Prospective Studies ; Surveys and Questionnaires

Epidermal necrolysis (EN) is a rare, but potentially life threatening disease, characterized by epidermal necrosis and sub-epidermal detatchment, and is predominantly medication-induced. Methazolamide is a sulfonamide derivative and carbonic anhydrase inhibitor used for lowering of intraocular pressure in glucomatous patients. Common side effects of methazolamide include metabolic acidosis, hypokalemia, tinnitus, transient myopia, and renal calculi; however, EN caused by methazolamide is very rare. We report on two cases of EN induced by methazolamide treatment and review previously published cases.
Acidosis ; Carbonic Anhydrases ; Humans ; Hypokalemia ; Intraocular Pressure ; Methazolamide ; Myopia ; Necrosis ; Tinnitus

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the potentially life-threatening, acute hypersensitivity reaction to inciting drugs. These diseases have been often associated with systemic carbonic anhydrase inhibitor such as acetazolamide or methazolamide in Korean and Japanese patients. Dorzolamide is a recently developed topical carbonic anhydrase inhibitor with few significant systemic adverse effects. To the best of our knowledge, there have been only a few reports of SJS or TEN caused by topical dorzolamide in the literature. We herein present two cases of TEN and one case of SJS related with topical use of dorzolamide. It should be emphasized that although rarely, topical dorzolamide may cause serious sulfonamide hypersensitivity such as SJS or TEN in the susceptible patient through the systemic absorption.
Absorption ; Acetazolamide ; Asian Continental Ancestry Group ; Carbonic Anhydrases ; Epidermal Necrolysis, Toxic ; Humans ; Hypersensitivity ; Methazolamide ; Stevens-Johnson Syndrome ; Sulfonamides ; Thiophenes

PURPOSE: To report three consecutive cases of methazolamide-induced Stevens-Johnson syndrome. CASE SUMMARY: We describe three patients who were all prescribed methazolamide for treatment of ophthalmologic conditions. A 29-year-old man and a 47- year-old woman were prescribed methazolamide (100 mg/day) for the treatment of central serous chorioretinopathy (CSCR). A 66-year-old woman was prescribed methazolamide (100 mg/day) for acute glaucoma of the left eye for approximately two weeks. After taking the methazolamide, three patients were showed the pururitic maculopapular rashes on the whole body and the vesicular eruptions of the oral mucosa and conjunctiva. On the basis of medication histories, characteristic skin lesions and mucosal involvement, we diagnosed all three patients with methazolamide-induced Stevens-Johnson syndrome. All three patients were hospitalized and treated with intravenous steroids and antihistamines. Two of the three cases showed conjunctival pseudomembranes. In two cases, the skin lesions worsened during the first week of treatment, and then resolved without complications over the next two to three weeks. The condition of the 47-year-old female patient deteriorated rapidly to toxic epidermal necrolysis due to sensitivity to sulfa antibiotics. HLA- A24, B59 and Cw1 were detected in all three cases. CONCLUSIONS: In 2008, domestic production of acetazolamide was halted in Korea. Because of this, methazolamide is expected to be prescribed by ophthalmologists more commonly than in previous years. Complete medical histories should be taken before prescribing methazolamide to patients. HLA typing should be conducted whenever possible to screen patients before prescription of methazolamide.
Acetazolamide ; Adult ; Aged ; Anti-Bacterial Agents ; Central Serous Chorioretinopathy ; Conjunctiva ; Epidermal Necrolysis, Toxic ; Exanthema ; Eye ; Female ; Glaucoma ; Histamine Antagonists ; Histocompatibility Testing ; HLA-B Antigens ; Humans ; Korea ; Methazolamide ; Middle Aged ; Mouth Mucosa ; Prescriptions ; Skin ; Steroids ; Stevens-Johnson Syndrome