Hydrogen cyanamide exposure: a case series from Pavia Poison Control Centre.

BACKGROUND: Hydrogen cyanamide is a plant growth regulator introduced in Italy as Dormex in 2000, but recalled from the market in 2008. It's currently not authorized in Europe. Inhalation/dermal contact may cause irritation/caustic burns, ingestion of severe organ damage and concomitant alcohol consumption disulfiram-like reaction due to aldehyde-dehydrogenase inhibition by hydrogen cyanamide. AIMS: To study all exposure cases referred to our centre, evaluating temporal and geographic distribution and analysing clinical manifestations, including the ones after alcohol consumption. METHODS: We retrospectively evaluated all hydrogen cyanamide exposures referred to our Poison Control Centre (January 2007-December 2021). For each case, age, sex, exposure route/year, geographical location, intent of exposure, alcohol co-ingestion, emergency department-admission Poison Severity Score, signs/symptoms and treatment were analysed. RESULTS: Thirty subjects were included. Median case/year was 1 [1; 2]: 79% occurred after market withdrawal, 92% in Sicily. All exposures were unintentional and work related; 41% of patients also co-ingested alcohol. Mean poison severity score at emergency department admission was 1.54, more severe when ingestion occurred. The most common signs/symptoms were flushing, secondary to peripheral vasodilation (41%), hyperaemia/erythema (29%), dyspnoea (25%), nausea (20%), vomiting (12%), oedema (12%), II-III degrees burns (12%) and pharyngodynia (12%). All patients were treated symptomatically and fully recovered. CONCLUSIONS: Hydrogen cyanamide exposure can lead to severe clinical manifestations. Despite its withdrawal from the Italian market, hydrogen cyanamide is still used: through PCC's crucial role in monitoring exposure to agricultural products efforts should be made to contrast illegal trade and increase awareness of its potential toxicity in those countries in which it's still legal.

Ground-glass hepatocellular inclusions are associated with polypharmacy.

Ground-glass (GG) hepatocytes are classically associated with chronic hepatitis B (HBV) infection, storage disorders, or cyanamide therapy. In a subset of cases, an exact etiology cannot be identified. In this study, we sought to characterize the clinical, histological, and ultrastructural findings associated with HBV-negative GG hepatocytes. Our institutional laboratory information system was searched from 2000 to 2019 for all cases of ground-glass hepatocytes. Ten liver biopsies with GG hepatocellular inclusions and negative HBV serology, no known history of storage disorders, or cyanamide therapy were reviewed. Half of the patients had history of organ transplantation and/or malignancy. These patients took on average 8.1 medications (range: 3-14) with the most common medications being immunosuppressive and health supplements. Histologically, GG hepatocytes show either peri-portal or centrizonal distribution. The inclusions are PAS-positive and diastase sensitive. Electron microscopy showed intracytoplasmic granular inclusions with low electron density, consistent with unstructured glycogen. In summary, GG hepatocytes are a rare finding in liver biopsies, but are more common in patients with hepatitis B. They can also be seen in HBV-negative patients who have polypharmacy. In these cases, they are the result of unstructured glycogen accumulation putatively due to altered cell metabolism.

[Cyanamide-ethanol reaction induced shock: report of a case and literature review].

Cyanamide is a known alcohol deterrent, and it may cause severe cyanamide-ethanol reaction if a patient consumes high amounts of alcohol during treatment. We report a rare case of cyanamide-ethanol reaction-induced shock in a 73-year-old man who was taking cyanamide for the treatment of alcohol dependence. The patient complained of acute onset of dyspnea after drinking. On arrival, he was in a state of shock. We immediately started hydration and administered 0.3 mg adrenaline by intramuscular injection. However, the patient's general condition did not improve. We could rescue him only after a high dose of adrenaline was administered by continuous intravascular injection. In general, in the treatment of cyanamide-ethanol reaction-induced shock, adrenaline or noradrenaline should be used instead of dopamine. Some cases of severe cyanamide-ethanol reactions have been recently reported in Japan. We performed a literature review and have discussed these cases in the text.

Disulfiram-like syndrome after hydrogen cyanamide professional skin exposure: two case reports in France.

Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.

The adverse effects of hydrogen cyanamide on human health: an evaluation of inquiries to the New Zealand National Poisons Centre.

INTRODUCTION: Hydrogen cyanamide is used in New Zealand to induce bud break in kiwifruit vines. The aim of this investigation was to evaluate the calls received by the New Zealand National Poisons Centre (NZNPC) attributed to acute hydrogen cyanamide exposure, and to ascertain the clinical effects of such exposures. METHODS: Call data from the NZNPC telephone collection databases regarding human hydrogen cyanamide exposures were analyzed retrospectively for the years 1990-2006. RESULTS: There were 68 human exposures, 69% were male and 22% female; 88% were adults and there were no suicide attempts. Common exposure routes were inhalation (56%) and skin contact (28%). The workplace accounted for 45% of calls. The predominant toxic effects were nausea and vomiting (29%), headache (22%), contact dermatitis (19%), and erythema (18%). DISCUSSION: Reported symptoms and signs were consistent with the expected effects of hydrogen cyanamide exposure. Other reports of similar exposures describe higher degrees of illnesses among workers using hydrogen cyanamide, which might have been because of lack of training, inadequate access to personal protective equipment, and the absence of engineering controls. CONCLUSIONS: Based on the calls received by the NZNPC, acute exposure to hydrogen cyanamide in the workplace or acute exposure to those living within the vicinity of its use may not pose a significant immediate threat to human health.

Contact dermatitis in dairy cattle caused by calcium cyanamide.

Nine of 250 cows on a dairy farm initially developed severe dermatitis on parts of their bodies that touched the floor, and it then spread over their entire body. The cause was suspected to be calcium cyanamide, which had been added to the material spread on the floor to prevent environmental mastitis. Experimental exposure of the skin of a cow to calcium cyanamide induced the same type of contact dermatitis, and histopathological investigations showed that it caused irritant and allergic reactions. To identify the cause of the dermatitis, a patch test with calcium cyanamide and its breakdown products, cyanamide, urea and ammonium bicarbonate, was carried out on four cows. Three of them had a positive reaction to calcium cyanamide and cyanamide; delayed and amplified reactions suggesting an allergic response were observed.

Allergic contact dermatitis with a fertilizer containing hydrogen cyanamide (Dormex).

Cyanamide is a chemical substance used in the treatment of chronic alcoholism as well in agriculture as a fertilizer. We report the case of a 28-year-old healthy non-atopic man that developed a severe skin eruption after the accidental penetration of a small amount of Dormex (a plant growth regulator containing cyanamide) through the patient's gloves. Patch tests revealed positive reactions to Dormex 1% pet. and cyanamide at a dilution of 0.1% pet. and 1% pet. We discuss the causes of sensitization in a patients that regularly used protective measures during anti-parasites treatments.

Cutaneous reactions simulating erythema multiforme and Stevens Johnson syndrome due to occupational exposure to a plant-growth regulator.

BACKGROUND: In India, hydrogen cyanamide (Dormex) is a plant growth regulator used mainly for the bud-breaking of grapevines. The use of this chemical may result in severe cutaneous reactions simulating erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: Studies were conducted on four seasonal grapevine workers who developed severe cutaneous reactions following the unprotected use of Dormex (hydrogen cyanamide). RESULTS: Two of the patients had EM-like skin lesions and the other two developed SJS-TEN-like skin lesions. A latent period of 5-7 days existed between the contact with the chemical and the development of the skin lesions. The histopathological picture was suggestive of EM. All the patients responded to systemic steroids and antihistamines. CONCLUSIONS: Hydrogen cyanamide may act as a hapten, initiating cytotoxic immunological attack on keratinocytes, resulting in EM- and SJS-TEN-like clinical picture. Awareness regarding such severe cutaneous reactions due to the inappropriate handling of Dormex is required. The use of personal protection equipment while handling agricultural chemicals is essential.

Problem drinking in relation to treatment outcome among opiate addicts in methadone maintenance treatment.

This study analyzed indicators of alcohol-related problems in opiate addicts before, during, and after leaving methadone maintenance treatment (MMT), in relation to illicit drug use and retention in treatment. The study was based on 204 patients, admitted to MMT for the first time between 1 January 1995 and 31 July 2000, and followed until 31 December 2000. Three measures were used to indicate alcohol use and alcohol-related problems; records of hospital care with an alcohol-related diagnosis, any treatment with alcohol-sensitizing drugs (disulfiram or calcium carbimide) during MMT, and results of the 5-hydroxytryptophol to 5-hydroxyindoleacetic acid ratio (5HTOL/5HIAA) in urine, a sensitive biomarker for recent drinking. Use of illicit drugs was determined by routine urine drug testing. About one third of the patients (n = 69) had a lifetime prevalence of hospital treatment for an alcohol-related diagnosis, 45 of whom had been hospitalized (mean 4.2 stays) prior to the start of MMT. There was a significant association (p<0.05) between the number of alcohol-related diagnoses prior to treatment and a positive 5HTOL/5HIAA test during MMT. The alcohol indicators first became positive on average 1.6 years after admission to treatment, compared with after about 4 months for illicit drugs. Use of cannabis or benzodiazepines was significantly associated with alcohol use. Female methadone patients with indications of alcohol-related problems relapsed more often into illicit drug use than did women without such indications (3.9 vs. 2.5 relapse periods/year; p<0.005), whereas no significant association was found for men. The results of the present study indicate that drinking problems among patients undergoing MMT is associated with an increased risk of relapse into illicit drug use and with discharge from treatment. Concurrent treatment of alcohol-related problems, including systematic monitoring of alcohol use, therefore should be recommended to reduce the risk for relapse into illicit drug use and improve overall treatment outcome in MMT.

Síndrome acetaldehídico por exposición laboral a cianamida de hidrógeno / Acetaldehyde syndrome after laboral exposition to hydrogen cyanamide

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Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: is there still a role for these drugs?

Disulfiram and calcium carbimide are two alcohol deterrants widely used in alcoholism treatment, however, there exist great concerns over their safety. Reports on hepatotoxicity, mainly related to disulfiram therapy, have been published. The hepatotoxic potential of calcium carbimide is less well characterized. Here, we describe four cases of liver damage related to this therapeutic group that were submitted to a Registry of hepatotoxicity and point out the limitations that we face when prescribing these compounds. A reassessment of the role of these compounds in the management of alcohol dependence is clearly needed.

Allergic contact dermatitis from cyanamide.

Cyanamide (carbimide or calcium carbimide) has been used to treat chronic alcoholism for more than 45 years. The skin reactions provoked by this medication are very rare and are generally associated with systemic reactions after ingestion of the product. However, allergic contact dermatitis has also been detected on persons who prepare cyanamide for administration to patients. We present a case of work-related allergic contact dermatitis from cyanamide that was confirmed by patch testing.

Cyanamide-induced aplastic anemia.

OBJECTIVE: To report a case of aplastic anemia in a patient treated with cyanamide, an alcohol-aversive drug. A 67-year-old man was admitted to hospital because of fever and pancytopenia. He had taken cyanamide for 6 months as an alcohol deterrent. No other risk factors for aplastic anemia were identified by interviewing the patient using a structured validated questionnaire. The results of bone-marrow biopsy showed severe aplastic anemia. Cyanamide was discontinued and the patient was treated according to a prespecified treatment protocol. One year after hospital admission, the patient was completely recovered with no need of immunosuppressive therapy. An objective causality assessment revealed that an adverse drug reaction was probable. DISCUSSION: As the efficacy of cyanamide has been questioned, due to the failure of various trials to show any benefit over placebo, its overall benefit/risk ratio should be reconsidered. The complete and rapid hematological recovery after discontinuation of the drug, and the absence of other factors that could explain the condition support the association of the present case of aplastic anemia with cyanamide. The mechanism remains unknown. Aplastic anemia is a rare but potentially serious adverse drug effect of cyanamide treatment. CONCLUSIONS: Given the poor evidence on the efficacy of cyanamide and the associated risk of aplastic anemia, its use in reducing alcohol consumption should be reconsidered.

Drug-induced hypersensitivity syndrome due to cyanamide associated with multiple reactivation of human herpesviruses.

Drug-induced hypersensitivity syndrome (DIHS), characterized by serious adverse systemic reactions in addition to skin rash, has unknown pathogenesis. Its association with human herpesvirus (HHV), mainly HHV-6, has been reported recently. A 46-year-old Japanese man is described in whom a generalized eruption developed about 1 month after taking cyanamide, a drug for alcoholism. This was associated with the following manifestations: high fever, lymphadenopathy, facial edema, marked leukocytosis with eosinophilia and atypical lymphocytes, lymphocytopenia, liver and renal dysfunction, and low IgG level. He was treated with 8 mg betamethasone daily and his condition improved, but he needed low-dose corticosteroid for almost 1 year because of several episodes of recurrence. HHV-6, HHV-7, herpes simplex virus (HSV), and cytomegalovirus (CMV) specific IgG titers showed more than a four-fold rise sequentially. Significant numbers of copies of HHV-6 and HHV-7 DNA were detected in the peripheral white blood cells by real-time polymerase chain reaction (PCR). HHV-6 and CMV DNA were detected in the serum by nested PCR. A patch test for cyanamide was positive. The diagnosis of DIHS due to cyanamide, which has never been reported as a causal drug of DIHS, accompanied by reactivation of not only HHV-6, but also HHV-7, CMV, and HSV, was made. Disturbance of the immune system was suggested by the persistent low level of IgG, and consecutive viral reactivation may have participated in the prolonged course in this case.

Disfunciones sexuales en el alcoholismo / Sexual dysfunction in alcoholism

La prevalencia de disfunciones sexuales en el alcoholismo es alta y oscila, según distintos estudios, entre el 3,2 por ciento y el 64,4 por ciento. El presente estudio tiene como objetivo investigar la frecuencia de este tipo de alteraciones en una muestra de pacientes alcohólicos que estaban en tratamiento por esta enfermedad. Así mismo, se pretende averiguar los factores que pueden influir en su génesis, además del alcohol. La muestra de estudio comprendía 183 personas, 150 varones y 33 mujeres cuya edad media era de 43 años. Se administró a los pacientes una encuesta autoaplicada y anónima que contenía el Cuestionario de Funcionamiento Sexual de LoPiccolo (SHF). Así mismo se determinaron los niveles de testosterona, estradiol y prolactina. Los resultados principales fueron: el funcionamiento sexual global era aceptable (puntuación global: 0,415 ñ 0,155) y significativamente mejor en los varones que en las mujeres; el 45 por ciento mantenía relaciones semanalmente, el 69 por ciento experimentaba deseo sexual durante la semana, el 81 por ciento de los varones no tenía problemas en alcanzar y mantener la erección y el 10 por ciento refería eyaculación precoz; en el grupo de mujeres, el 10 por ciento refería vaginismo y el 5 por ciento dolor en el coito. Los niveles de testosterona, estradiol y prolactina estaban en el rango normal; ni el diagnóstico, ni la cantidad de gramos de alcohol consumido, ni la situación de abstinencia o consumo influía en el funcionamiento sexual global. La presencia de enfermedades somáticas y la ingestión de medicamentos, principalmente Cianamida cálcica, empeoraban significativamente el funcionamiento sexual global (AU)

The prevalence of sexual dysfunction in alcoholism very frequent and fluctuates between 3.2% and 64.4 %, according different studies. The aim of this research is to study sexual dysfunction frequency in a sample of alcoholic patients who were undergoing treatment for this illness. We also analyse the factors, in addition to alcohol, that could influence these disorders. The study consists of an anonymous, selfadministered questionnaire on sexual behaviour, designed by LoPiccolo (SHF), with a sample of 183 individuals, 150 men and 33 women with an average age of 43 years. Levels of testosterone, estradiol and prolactin were also measured. The main results were as follows: overall sexual functioning was acceptable (overall score: 0.415 ± 0.155), and was significantly better in men than in women; 45% had sexual relations weekly, 69% experienced sexual desire during the week, 81% of men had no problems in reaching and maintaining an erection, 10% referred to premature ejaculation. In the group of women, 10% suffered from vaginismus and 5% from pain during coitus. Levels of testosterone, estradiol and prolactin were within the standard range. Neither the diagnosis, the amount of alcohol consumed nor abstinence or consumption of alcohol influenced overall sexual behaviour. The presence of somatic diseases and the intake of medicaments, particularly calcium cyanamide, significantly diminish general sexual performance (AU)

Dermatitis alérgica de contacto por Colme (cianamida cálcica) / Allergic contact dermatitis due to Colme® ( calcium cyanamide)

La cianamida en su forma libre y como sal de calcio se emplea para el tratamiento en la deshabituación de alcohólicos por su efecto sobre el metabolismo del etanol al inhibir la aldehído desbidrogenasa. Generalmente es un fármaco que se tolera bien aunque se han descrito reacciones adversas, especialmente a nivel cutáneo, algunas debidas a mecanismos de hipersensibilidad. Se describe el caso de una enfermera de psiquiatría que presentó lesiones eccematosas en las zonas de contacto con el preparado Colme® (cianarnida cálcica). Las pruebas epicutáneas con Colme® al 10% en parche abierto y cerrado resultaron diagnósticas. Se presenta un caso de dermatitis alérgica de contacto por Colme® de carácter ocupacional que raramente se ha descrito a pesar de su uso frecuente (AU)

Cyanarnide, both in its free form and as the calcium salt, is used in the dehabituation treatment of alcoholics because of it effect on ethanol metaboli m through inhibition of the enzyme aldehyde dehydrogenase. The drug is usually well tolerated; however, adverse reactions have been reported, particularly involving the skin, in sorne instances with a hypersensitivity mechanism. We report the case of a nurse in the Psychiatry departrnent who consulted because of eczematous le ions in the areas of contact with the drug Colme® (calcium cyanamide). The epicutaneous tests with Colme® ar 10% concentration, both as open and as occlusion patches, confirmed the diagnosis.We report one case of occupational allergic contact dermatitis due to Colme®, a condition seldom described despite the widespread use of the drug (AU)

Comparison of cyanamide and placebo in the treatment of alcohol dependence of adolescents.

AIMS: About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that cyanamide may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term cyanamide treatment in alcohol dependence of adolescents. METHODS: In this, double-blind, placebo-controlled study, we recruited 26 patients, aged 16-19 years, with chronic (frequent and regular) or episodic (frequent, but irregular) alcohol dependence. Patients were randomly allocated treatment with cyanamide (200 mg daily) or a placebo for 90 days. Patients were assessed on the day the treatment was started, and on days 30 and 90, by interview, self-report, questionnaire and laboratory screening. Patients were classified as abstinent, relapsing or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. RESULTS: The cyanamide (n = 13) and placebo (n = 13) groups were well matched in terms of baseline demographic and alcohol-related variables. Mean cumulative abstinence duration was significantly greater in the cyanamide group than in the placebo group. Apart from occasional diarrhoea, there was no difference in side effects between groups. CONCLUSIONS: Cyanamide seems to be an effective and well tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for the treatment of some adolescent alcohol-dependent patients. Because of reported hepatotoxic, haematological and dermatological side effects, patients should be observed continuously by experienced clinicians. Further studies are necessary to prove the efficacy of cyanamide in adolescents.

Use of a monoclonal antibody against Lafora bodies for the immunocytochemical study of ground-glass inclusions in hepatocytes due to cyanamide.

AIMS: Ground-glass inclusions (GGIs) in hepatocytes are known to be associated with cyanamide treatment in patients with alcohol dependency. The purpose of this study was to assess the reactivity of a monoclonal antibody (MAb) raised against polyglucosan and to detect early events in GGI formation. METHODS AND RESULTS: Formalin-fixed paraffin-embedded liver tissues from four patients treated with cyanamide were used. Sections were stained with haematoxylin and eosin and periodic acid-Schiff with and without diastase digestion, and were immunohistochemically stained with the MAb. For electron microscopic study, routinely processed liver tissue from one patient was examined with conventional and immunoelectron microscopy with use of the MAb. All specimens from the four cyanamide-treated patients contained GGIs in the cytoplasm of hepatocytes, and these GGIs reacted intensely with the MAb. Fully developed GGIs contained various organelles, whereas early ones consisted primarily of glycogen granules and dilated smooth endoplasmic reticulum. In immunoelectron microscopic preparations, gold particles were located within GGIs, and the immunolabelled organelles appeared to be glycogen granules. CONCLUSIONS: This novel MAb is useful for the detection of GGIs caused by cyanamide. Our results support the idea that GGI formation may result from specific abnormalities in glucose metabolism.