Hoigné's syndrome, an uncommon mimicker of anaphylaxis: Systematic literature review.

The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.

Acute myocardial infarction in a patient suffering from penicillin-induced laryngeal edema : Kounis syndrome aggravated by adrenaline.

Kounis syndrome or allergic angina is defined as the coincidental occurrence of chest pain and allergic reactions accompanied by clinical and laboratory findings of classical angina pectoris. It is triggered by the action of potent vasoactive and inflammatory mediators, which are released from the mast cells during the allergic reaction. Epinephrine is a life-saving medication in anaphylaxis; however, it can aggravate ischemia and induce coronary vasospasm and arrhythmias. Here, we present a patient with Kounis syndrome that was caused by intramuscular injection of procaine penicillin G, and in whom epinephrine administration for treatment of laryngeal edema had provoked severe myocardial ischemia.

Maternal mortality in a rural Tanzanian hospital: fatal Jarisch-Herxheimer reaction in a case of relapsing fever in pregnancy.

Relapsing fever is a disease caused by one of the species of Borrelia. It is often misdiagnosed as malaria and can have fatal complications such as the Jarisch-Herxheimer reaction (JHR) after the commencement of treatment with antibiotics. A 19-year-old Tanzanian woman was admitted after a term home delivery that day. She presented with a 2 day history of fever, headache, general body malaise and vomiting. She was misdiagnosed as having severe malaria and was treated with quinine. The blood slide showed Borrelia duttoni. The patient continued treatment with procaine penicillin fortified for relapsing fever. Several hours later the woman died, probably due to JHR. This case of a patient with relapsing fever who died from a JHR stresses the importance of adequate diagnosis and treatment which should include careful monitoring, especially for the first hours after starting antibiotics.

Safety and efficacy of simplified antibiotic regimens for outpatient treatment of serious infection in neonates and young infants 0-59 days of age in Bangladesh: design of a randomized controlled trial.

BACKGROUND: Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7-10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections. METHODS: We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. The reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant's home. The primary outcome is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. The sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013. DISCUSSION: The trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. The approach although effective was not widely accepted in part because of feasibility concerns about the large number of injections. The proposed research that includes fewer doses of parenteral antibiotics if shown efficacious will address this concern.

Adverse effects associated with inadvertent intravenous penicillin G procaine-penicillin G benzathine administration in two dogs and a cat.

CASE DESCRIPTION: 2 dogs and a cat were inadvertently given penicillin G procaine-penicillin G benzathine IV instead of propofol during induction of anesthesia for routine dental prophylaxis. One dog and the cat required hospitalization because of severe neurologic impairment and cardiopulmonary arrest (cat); the remaining dog did not develop any clinical signs. CLINICAL FINDINGS: In the 2 animals that developed signs consistent with an immediate adverse reaction, clinical signs included muscle tremors, seizures, blindness, vocalization, agitation, and transient loss of vision. Hypothermia, pruritus, hypotension, and cardiac arrest were also documented. TREATMENT AND OUTCOME: The 2 affected patients responded to treatment with anticonvulsant medications, centrally acting muscle relaxants, sedation, and intensive supportive care including IV fluid administration and oxygen supplementation as needed. Cardiopulmonary cerebral resuscitation was performed successfully in the cat. The dog that did not develop any clinical signs was not treated. The 2 affected patients recovered fully and were discharged from the hospital after 3 to 4 days with no apparent sequelae. CLINICAL RELEVANCE: Penicillin G procaine-penicillin G benzathine and propofol are common drugs in veterinary practice and may both be administered to patients undergoing elective procedures. Because of their similar milky white appearance, veterinarians should label syringes and take care to avoid this medication error. There is no specific antidote for penicillin orprocaine toxicosis. Aggressive and immediate treatment is required in patients that develop an adverse reaction to ensure a successful outcome.

Clinical signs and etiology of adverse reactions to procaine benzylpenicillin and sodium/potassium benzylpenicillin in horses.

Case reports of 59 horses reacting adversely to procaine benzylpenicillin or to sodium or potassium benzylpenicillin in Sweden in 2003-2005 were obtained through contacts with horse-owners. For the assessment of the reports, various parameters were evaluated, such as the times to the reactions, information on previous penicillin treatment, the clinical signs and the actions taken in the reacting horses. Among the reports, two horses had received sodium or potassium benzylpenicillin intravenously, whereas the remaining 57 horses had been treated with procaine benzylpenicillin intramuscularly. Allergy may underlie the adverse reactions in the horses given sodium and potassium benzylpenicillin, and in a few of the horses given procaine benzylpenicillin. However, in most horses in the latter group, the clinical signs may be due to the toxic effects of procaine. In these horses, the dominating clinical signs were locomotor and behavioral changes. Some risk factors may enhance the probability that horses react to procaine. One is repeated injections, which increase the likelihood of intravascular administration and also may increase the sensitivity to procaine due to neuronal sensitization (kindling). Procaine is rapidly hydrolyzed by plasma esterases to nontoxic metabolites. When high amounts of procaine enter the circulation, the hydrolyzing capacity may be exceeded and toxicity occurs. Analyses of plasma esterases from reacting horses showed lower activity than in nonreacting control horses. Low esterase activity may increase the possibility of procaine toxicity and constitute another risk factor.

[Hoigne's syndrome]. / Síndrome de Hoigne.

BACKGROUND: Hoigne's syndrome is a pseudoanaphylactic or pseudoallergic reaction that occurs after intramuscular administration of penicillin G procaine or benzathine. These are usually embolic toxic reactions possibly due to vascular occlusion by large crystals of the penicillin salts. We report a case of Hoigne's syndrome. CASE REPORT: A 44-year-old woman received 1,200,000 U.I. of intramuscular procaine penicillin once daily for treatment of acute amygdalitis. Immediately after the second dose the patient developed mental confusion, visual and auditory hallucinations, perceived changes of body shape, swelling of the tongue and a fear of impending death. Penicillin allergy study (serum-specific IgE levels, skin tests and provocation test) was performed. The diagnosis of Hoigne's syndrome was confirmed by negative oral challenge test with penicillin. CONCLUSIONS: Hoigne's syndrome is a pseudoanaphylactic reaction that must be differentiated from authentic anaphylactic shock due to penicillin. This distinction allows treatment to be continued in Hoigne's syndrome, whereas it is contraindicated in anaphylactic shock.

Intramuscular bipenicillin vs. intravenous penicillin in the treatment of erysipelas in adults: randomized controlled study.

The objective of the study was to evaluate the efficacy of intramuscular penicillin: mixture of benzyl penicillin and procain penicillin (2 MU x 2 times daily) and intravenous benzyl penicillin (4 MU x 6 times daily) in the treatment of hospitalized adult patients with erysipelas. A prospective randomized unicentric trial was conducted. In total, 112 patients entered the study; 57 in the intramuscular group and 55 patients in the intravenous group completed the trial. The failure rate was 14% for intramuscular group and 20% for the intravenous group (P = 0.40). Local complications such as of the leg abscesses were observed in the two groups (intravenous 9.1%, intramuscular 7%; P = 0477). Of the patients treated with intravenous benzyl penicillin, 25.5% presented complications related to the route (venitis). Intramuscular penicillin should be considered an effective and well-tolerated treatment of erysipelas in adult patients.

Sudden sensorineural hearing loss following intramuscular administration of penicillin.

We report a case of sudden hearing loss in a patient with acute exudative tonsillitis, occurring 15 minutes after the intramuscular administration of penicillin. Audiological evaluation documented a profound sensorineural hearing loss of the cochlear type. The mechanism of the hearing loss was probably an immediate hypersensitivity (type I) allergic drug reaction. Penicillin is used frequently for the treatment of several infections. Allergic reactions to penicillin are well known and include urticaria, maculopapular exanthems, angio-oedema, bronchospasm and anaphylaxis, but sudden hearing loss has never been recorded.

Update: Interim recommendations for antimicrobial prophylaxis for children and breastfeeding mothers and treatment of children with anthrax.

Ciprofloxacin or doxycycline is recommended for antimicrobial prophylaxis and treatment of adults and children with Bacillus anthracis infection associated with the recent bioterrorist attacks in the United States. Amoxicillin is an option for antimicrobial prophylaxis for children and pregnant women and to complete treatment of cutaneous disease when B. anthracis is susceptible to penicillin, as is the case in the recent attacks. Use of ciprofloxacin or doxycycline might be associated with adverse effects in children, and liquid formulations of these drugs are not widely available. This notice provides further information about prophylaxis and treatment of children and breastfeeding mothers, including the use of amoxicillin.

[Hoigne syndrome as an acute non-allergic reaction to different drugs: case reports]. / Zespól Hoigne jako ostra niealergiczna reakcja na rózne leki--opis przypadków.

In 1959 Hoigne described the first cases of pseudo-anaphylactic reactions induced by intramuscular administration of procaine penicillin G. This complication, characterized by acute psychological and neurological manifestations, is still of current interest. We report cases of patient, whose Hoigne syndrome was not due to procaine penicillin G (i.e. lidocaine, edan, azlocillin, gentamycin, klaritromycin and cefuroxime). It is accepted that Hoigne syndrome can be caused by lidocaine. Further Stell i.m. and Ojo OA published similar case report of Amoxycillin-induced hallucinations. These clinical observations indicate also that using term "acute non-allergic reaction to procaine penicillin G" as synonym of Hoigne syndrome is not precise. Further classification of the reaction among psychic disturbances or adverse drug reactions is very difficult. Much of literature is devoted to the differentiation from anaphylaxis rather than other symptoms of main disease or side effects. Harmful effect of main disease is very likely. Lidocaine was taken intravenously by patient with diabetes and heart attack or locally with chronic hepatitis during topical anesthesia. Benzylpenicillin, azlocycillin, gentamycin, klaritromycin and cefuroxime was used during serious bacterial infections. These observations indicate that pathogenesis of Hoigne syndrome may be associated with main disease and organic brain disease. Then procaine kindling mechanism partly explain Hoigne syndrome. Therefore pathogenesis, definition, differentiation and classification of this complication is still unclear.

Hoigne's syndrome, kindling, and panic disorder.

A review of Hoigne's syndrome (HS) is presented, and 47 cases of putative procaine penicillin-induced HS are discussed within the context of kindling models of human psychopathology. Sixty percent of the individuals with HS in our retrospective study reported a lifetime history of panic disorder. The risk factors and causal relationships among repeated injection of procaine penicillin, HS, and anxiety disorders, particularly panic disorder, require further investigation.

Immediate nonallergic psychotic reaction to intramuscular procaine penicillin.

BACKGROUND: Though little known by medical personnel, an immediate nonallergic psychotic reaction to intramuscular procaine penicillin has been reported occasionally from many countries since 1951. MATERIALS AND METHODS: A case report describes a patient whose violent behavior, provoked by this reaction, resulted in legal action taken against him. Two other nonviolent cases are presented and are followed by a review of the literature. RESULTS: Signs and symptoms of this reaction that appears to be to the procaine component resemble a pressor response and are therefore contrary to the signs and symptoms of an anaphylactic reaction. Anxiety, hallucinations, hypertension, and tachycardia are characteristic. The reaction is self-limited. Long-term psychologic sequelae might be averted by adequate reassurance. CONCLUSIONS: The importance of procaine penicillin as an essential drug in many parts of the world should not be diminished; however, recognition of acute nonallergic psychotic reactions is of paramount importance to assure proper patient management and to avoid misinterpretation of aggressive behavior.

[Procaine kindling in acute non-allergic reaction to procaine penicillin G]. / Kindling prokainowy w ostrej niealergicznej reakcji na penicyline prokainowa.

On the basis of the analysis of acute nonallergic reaction to a course of procaine penicillin G, the authors have stated that symptoms of this reaction result from the irritation of temporal limbic structures. The authors think that it is connected with procaine kindling mechanism, the procaine component of the drug.