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Ketotifen and systemic mastocytosis
Correspondence
Ketotifen and systemic mastocytosis To the Editor: The article by Kettelhut et al.’ demonstrated that ketotifen, 2 mg daily, offers no advantage over hydroxyzine in the treatment of pediatric mastocytosis. However, I wonder whether the dose of ketotifen used in their study is indeed the optimal dose. I have followed a 42-year-old white man with systemic mastocytosis for several years. During the past 12 months, his cutaneous symptoms were fairly well controlled by doxepin, 50 mg, four times a day (q.i.d.), ranitidine, 150 mg three times a day, and hydroxyzine, 50 mg at bedtime. However, neuropsychiatric symptoms such as short attention span and inability to concentrate and diarrhea are not controlled by the above medications. Commercially available cromolyn capsules, up to 200 mg q.i.d. for a few weeks, only alleviated gastrointestinal symptoms. A compassionate-use trial of ketotifen, 2 mg q.i.d. daily, controlled his cutaneous, neuropsychiatric, and gastrointestinal symptoms. Flare up of symptoms always occurred if ketotifen was decreased to 6 mg daily; 24-hour urinary histamine level before the initiation of ketotifen therapy was 228 p.gl24 hours and decreased to 116 pgl24 hours after 2 weeks of ketotifen therapy. It further decreased to 64 p,g/24 hours after 6 weeks of ketotifen therapy, 8 mg daily. My patient wrote “Dear Dr. Ting: I would like to thank you for your help and patience in helping me to better manage my mastocytosis. The Zaditen has worked a miracle on me. I feel like a person who is on a furlough after being in a chemical prison for over 20 years. I don’t think I have felt better since my senior year in high school 25 years ago. I have finished my secondmanuscript in 2 months and starting on the third. Again thank you. signed RE.” In 1983 Czarnetzki’ reported in a double-blind, crossover study that ketotifen, 2 mg daily, significantly reduced the daily symptom scores of pruritus and whealing; however, none of the 10 adult patients with u&aria pigmentosa that she studied had gastrointestinal or neuropsychiatric symptoms. In addition, no urinary histamine data were available to augment her clinical findings. It appears that larger doses of ketotifen are needed to control this patient’s multisystem symptoms that are presumably related to the pharmacologic effects of released mediators from mast cells.’ A large-scale, clinical, doubleblind study should be done in the future to evaluate the efficacy/safety of high-dose ketotifen in patients with systemic mastocytosis who have multisystem symptoms and fail to respond to H, and H, antagonists and oral cromo1yn.4 Stanislaus Ting, MD 1141 Mall Drive Las Cruces, NM 88001
818
REFERENCES Kettelhut BV, Berkebile C, Bradley D, Metcalfe DD. A doubleblind, placebo-controlled,crossovertrial of ketotifen versushydroxyzine in the treatmentof pediatric mastocytosis.J ALLERGY CLIN IMMUNOL 1989;83:866.
Czarnetzki BM. A double-blind, crossover study of the effect of ketotifen in u&aria pigmentosa. Dermatologica 1983;166: 44. Lewis RA. Mastocytosis. J ALLERGY CLIN IMMUNOL 1984;74: 755. Lichtenstein LM, Fauci AS. Current therapy in allergy, immunology, and rheumatology. Toronto: BC Decker, 198% 198651.
Bronchial hyperreactivity and cough induced by angiotensin-converting enzyme-inhibitor therapy To the Editor: Cough is a recognized side effect of angiotensinconverting enzyme inhibitors (ACEIs). I-3The mechanism(s) of action of ACEI-induced coughing remain(s) unclear. Recent studies suggest that ACEIs increase the sensitivity of cough reflex.+ * The existence of bronchial hyperreactivity in patients who cough after receiving ACE1 is controversial. There have been occasional case reports of increased wheezing associated with ACE1 therapy in subjects with asthma. The results of inhalation challenges in patients with no prior history of asthma have been mixed with a study of negative methacholine challenges6 and studies of positive methacholine’ and histamine* challenges in patients with prior bronchial hyperreactivity, which increased after ACE1 treatment.8 Recently, we have studied two hypertensive sisters without asthma, aged 63 and 65 years, respectively. They developed persistent cough during captopril treatment, which resolved when the therapy was stopped. Two months after the resolution of coughs, we rechallenged both patients with captopril, 150 mg daily, for the following 5 weeks. Both lung function and methacholineinhaled tests were performed 7 days before the challenge and, later, were measured weekly for the next 9 weeks. At the same time, patients daily monitored morning and evening peak expiratory flow rate and recorded the occurrence of cough and other respiratory symptoms on a scale of 0 to 3. A few days after the captopril rechallenge, both patients complained of a dry cough, which progressively increased until the drug was withdrawn. They made no reference to dyspnea or wheezes. Before rechallenge, lung function and methacholineinhaled tests revealed no abnormalities. Two weeks after the introduction of captopril, one patient had a significant fall in airway conductance that did not return to normal
Ketotifen and systemic mastocytosis To the Editor: The article by Kettelhut et al.’ demonstrated that ketotifen, 2 mg daily, offers no advantage over hydroxyzine in the treatment of pediatric mastocytosis. However, I wonder whether the dose of ketotifen used in their study is indeed the optimal dose. I have followed a 42-year-old white man with systemic mastocytosis for several years. During the past 12 months, his cutaneous symptoms were fairly well controlled by doxepin, 50 mg, four times a day (q.i.d.), ranitidine, 150 mg three times a day, and hydroxyzine, 50 mg at bedtime. However, neuropsychiatric symptoms such as short attention span and inability to concentrate and diarrhea are not controlled by the above medications. Commercially available cromolyn capsules, up to 200 mg q.i.d. for a few weeks, only alleviated gastrointestinal symptoms. A compassionate-use trial of ketotifen, 2 mg q.i.d. daily, controlled his cutaneous, neuropsychiatric, and gastrointestinal symptoms. Flare up of symptoms always occurred if ketotifen was decreased to 6 mg daily; 24-hour urinary histamine level before the initiation of ketotifen therapy was 228 p.gl24 hours and decreased to 116 pgl24 hours after 2 weeks of ketotifen therapy. It further decreased to 64 p,g/24 hours after 6 weeks of ketotifen therapy, 8 mg daily. My patient wrote “Dear Dr. Ting: I would like to thank you for your help and patience in helping me to better manage my mastocytosis. The Zaditen has worked a miracle on me. I feel like a person who is on a furlough after being in a chemical prison for over 20 years. I don’t think I have felt better since my senior year in high school 25 years ago. I have finished my secondmanuscript in 2 months and starting on the third. Again thank you. signed RE.” In 1983 Czarnetzki’ reported in a double-blind, crossover study that ketotifen, 2 mg daily, significantly reduced the daily symptom scores of pruritus and whealing; however, none of the 10 adult patients with u&aria pigmentosa that she studied had gastrointestinal or neuropsychiatric symptoms. In addition, no urinary histamine data were available to augment her clinical findings. It appears that larger doses of ketotifen are needed to control this patient’s multisystem symptoms that are presumably related to the pharmacologic effects of released mediators from mast cells.’ A large-scale, clinical, doubleblind study should be done in the future to evaluate the efficacy/safety of high-dose ketotifen in patients with systemic mastocytosis who have multisystem symptoms and fail to respond to H, and H, antagonists and oral cromo1yn.4 Stanislaus Ting, MD 1141 Mall Drive Las Cruces, NM 88001
818
REFERENCES Kettelhut BV, Berkebile C, Bradley D, Metcalfe DD. A doubleblind, placebo-controlled,crossovertrial of ketotifen versushydroxyzine in the treatmentof pediatric mastocytosis.J ALLERGY CLIN IMMUNOL 1989;83:866.
Czarnetzki BM. A double-blind, crossover study of the effect of ketotifen in u&aria pigmentosa. Dermatologica 1983;166: 44. Lewis RA. Mastocytosis. J ALLERGY CLIN IMMUNOL 1984;74: 755. Lichtenstein LM, Fauci AS. Current therapy in allergy, immunology, and rheumatology. Toronto: BC Decker, 198% 198651.
Bronchial hyperreactivity and cough induced by angiotensin-converting enzyme-inhibitor therapy To the Editor: Cough is a recognized side effect of angiotensinconverting enzyme inhibitors (ACEIs). I-3The mechanism(s) of action of ACEI-induced coughing remain(s) unclear. Recent studies suggest that ACEIs increase the sensitivity of cough reflex.+ * The existence of bronchial hyperreactivity in patients who cough after receiving ACE1 is controversial. There have been occasional case reports of increased wheezing associated with ACE1 therapy in subjects with asthma. The results of inhalation challenges in patients with no prior history of asthma have been mixed with a study of negative methacholine challenges6 and studies of positive methacholine’ and histamine* challenges in patients with prior bronchial hyperreactivity, which increased after ACE1 treatment.8 Recently, we have studied two hypertensive sisters without asthma, aged 63 and 65 years, respectively. They developed persistent cough during captopril treatment, which resolved when the therapy was stopped. Two months after the resolution of coughs, we rechallenged both patients with captopril, 150 mg daily, for the following 5 weeks. Both lung function and methacholineinhaled tests were performed 7 days before the challenge and, later, were measured weekly for the next 9 weeks. At the same time, patients daily monitored morning and evening peak expiratory flow rate and recorded the occurrence of cough and other respiratory symptoms on a scale of 0 to 3. A few days after the captopril rechallenge, both patients complained of a dry cough, which progressively increased until the drug was withdrawn. They made no reference to dyspnea or wheezes. Before rechallenge, lung function and methacholineinhaled tests revealed no abnormalities. Two weeks after the introduction of captopril, one patient had a significant fall in airway conductance that did not return to normal