Basophilic Chronic Granulocytic Leukaemia with Hyperhistaminaemia

Abstract

Two patients with typical Philadelphia chromosome positive chronic granulocytic leukaemia (CGL) developed an accelerated phase of the disease characterized by an increase white blood cell count and marked basophilia in the bone marrow and peripheral blood. Histamine levels were extremely high in both patients. Hyperhistaminaemia was manifested as wheezing, urticaria, diarrhoea, and pruritus in one patient and as peptic ulcer disease and peripheral oedema in both patients. In one case, gastric acid studies revealed a very high basal to stimulated ratio (BAO/MAO). Treatment with the investigational agent metiamide, an H2 receptor histamine antagonist, resulted in marked improvement in symptoms and reduction in gastric acid output. Extreme basophilia in CGL may be associated with hyperhistaminaemia, and manifestations of both the H1 and H2 type may occur.

Acute basophilic leukaemia and translocation t(X;6)(p11;q23)

“…These clinical manifestations might be caused by hypersecretion of gastric acid and pepsin, not documented in our patients, but already described in malignancies with extreme basophilia and subsequent hyperhistaminaemia (Youman et al, 1973;Rosenthal et al, 1977;Anderson et al, 1988;Olinger et al, 1976).…”

Prophylaxis of Symptoms of Hyperhistaminemia after the Treatment of Acute Promyelocytic Leukemia with <i>All-Tran</i><i>s</i> Retinoic Acid

“…The symptoms of hyperhistaminemia via H2 receptors actually seemed to be prevented by treatment with an H2 receptor antagonist, fa motidine, whereas wheezing, the symptom mediated by H, receptors, was improved by administration of chlorpheni ramine. Treatment with antihistaminic agents was re ported to result in marked improvement in symptoms of hyperhistaminemia in patients with basophilic chronic granulocytic leukemia [13,14]. Severe symptoms such as shock, peptic ulceration and flushing were reported after treatment with all-tmns retinoic acid in a patient with APL and basophilia although a histamine H2-rcccptor antag onist had been administered [3], but wheezing was not re ported.…”

“…Basophilia is often en countered in patients with chronic myeloproliferative dis orders, and symptoms due to basophilia-associated hyper histaminemia were reported [13][14][15]. The severity of the symptoms seemed to depend on the level of histamine, es pecially in plasma.…”

The flushing patient: Differential diagnosis, workup, and treatment

“…Other rare causes of flushing include sarcoidosis, especially the lupus pernio variant, wherein the diffuse granuloma underlies dilated blood vessels 1 ; mitral stenosis, which may cause a malar flush with cyanosis due to an uncertain mechanism 4 ; ''dumping syndrome,'' a constellation of facial flushing with tachycardia, sweating, dizziness, weakness, and gastrointestinal disturbances that occurs in patients after gastric surgery upon ingestion of food or hot fluid or upon infusion of hypertonic glucose 1,8,90 ; androgen deficiency in men after testicular injury, after orchiectomy, or due to pituitary tumor 91,92 ; acute arsenic intoxication 93 ; POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins, and skin changes) 94 ; basophilic granulocytic leukemia, via increased histamine production and associated with symptoms of wheezing, urticaria, diarrhea, and pruritus 6,95 ; bronchogenic carcinoma, possibly via overproduction of adrenocorticotropic hormone 96,97 or VIP 6 ; malignant histiocytoma, neuroblastoma, and ganglioneuroma, wherein flushing also may be related to increased production of VIP 6 ; postherpetic gustatory flushing and sweating in the distribution of the scarred trigeminal nerve 8 ; surgeries in the periaortic region that involve traction on the mesentery and thus may provoke prostacyclin release 7,98 ; Leigh syndrome, also known as subacute necrotizing encephalomyelopathy, which may have a prodrome of flushing that turns to pallor, sweating, drowsiness, lethargy, and restlessness, and is associated with increased levels of endorphins in the brain and spinal fluid 6 ; and Rovsing syndrome in patients with horseshoe kidney that may present with flushing, abdominal pain, and nausea, all of which are relieved by the anteflexed position. 6,8 Flushing may also be a feature of homocystinuria, 99 which typically presents with malar flushing, and of hyperthyroidism.…”