Wanye Syndrome

The structural formula of penicillin G, a drug whose reaction was first described by Rolf W. Wannier

The first such reaction to procyl benzylpenicillin was recorded in 1948 ^[2] . In 1951, Batchelor hypothesized his embolic origin. The syndrome was first investigated in detail in 1959 by Swiss physician Rolf W. Wagnier ( German Rolf Hoigné ), who described cases of pseudo-anaphylactic reactions after intramuscular administration of penicillin G to patients ^[3] .

In a narrower sense, Wagnier syndrome that occurs when antibiotics are administered is called “antibiomania” ( dr. Greek ἀντί - against, βίος - life, μανία - insanity) ^[4] .

The incidence is from 1: 1000 to 1: 3000 among those who have been injected with benzylpenicillin procaine ^[2] . Despite the fact that most cases are described in adult patients, it is also found in pediatric practice ^[5] . The syndrome is 6 times more common in men ^[6] .

It was previously believed that this syndrome can be caused solely by benzylpenicillin procaine ^[7] . However, in addition to the classical cases described by R.V. Wanier and caused by benzylpenicillin procaine (penicillin G procaine), a number of reactions have been recorded caused by other prolonged action penicillins: benzathine benzylpenicillin, including, in combination with benzylpenicillin procaine in the form of the drug “Bicillin- 5 "and azlocillin ^[8] , according to other observations, the syndrome can cause much less often:

1. Other antibiotics:
   1. Quite often ^[9] hallucinations caused by Wannier syndrome are observed with the use of semisynthetic penicillin amoxicillin ^{[8] [10]} .
   2. Cephalosporins : cefuroxime ^[8] .
   3. Macrolides : clarithromycin ^[8] .
   4. Aminoglycosides : gentamicin ^[8] .
2. Antihistamines : desloratadine ^[8] .
3. Local anesthetics : lidocaine ^[8] .

There are 2 theories of the pathogenesis of Wannier syndrome: the toxic and the so-called theory of limbic ( English kindling - ignition, kindling, ignition).

According to R.V. Guanye himself, who adhered to the first theory, the syndrome is a “toxic-allergic reaction” ^[11] . It was previously believed that Wanier syndrome is caused by the administration of procaine benzylpenicillin intravenously , as a result of which its crystals cause microembolism of the vessels of the brain and lungs ^[12] . Getting the drug into the vascular bed is also possible with a violation of the injection technique or repeated injections at a limited point of the buttock ^[7] . At the same time, this theory does not fully disclose the pathogenesis of the syndrome and does not explain its occurrence when using other drugs. In addition, during autopsy and during experiments on animals, microemboli in the brain were not detected ^[2] ; cases of thromboembolism of the pulmonary artery , which would result in Wannier syndrome, are not described ^[13] . However, it is possible that their absence can be caused by the fast solubility of crystals.

The Kindling theory was a further development of the toxic theory. According to this theory, low-intensity stimuli , initially unable to elicit a response, after their repeated repetition cause physiological and behavioral changes . They reduce the seizure threshold and have secondary effects on other parts of the brain, including the limbic system. Indirectly, the Kindling theory is supported by the fact that acute manifestations of Wanier syndrome are similar to paroxysmal symptoms of temporal and limbic epilepsy ^[14] . Among other drugs, local anesthetics have a kinetic effect on the limbic system: lidocaine, procaine (novocaine) and cocaine previously used for this purpose, which is currently used as a drug ^[2] . It was confirmed in experiments on laboratory animals and is described in patients who received intravenous lidocaine for the treatment of arrhythmias and in cocaine addicts. This effect has been proven in procaine.

In cases of the use of amoxicillin, which does not contain local anesthetics, this theory is doubtful ^[10] . However, it is known that penicillin itself, being an antagonist of GABA , can also cause a kindling effect ^[14] .

A possible association of the pathogenesis of Wagnier syndrome with abnormal dominance ^{[15] of the} cerebral hemispheres, which is more often observed in men, which generally correlates with the epidemiology of this disorder ^[6] .

The pathogenesis of Wanier syndrome has not been fully studied ^[8] . In particular, it is difficult to carry out differential diagnostics with the main symptoms of the disease, in the treatment of which the medication was used and its side effects not associated with Wannier syndrome. At the same time, the symptoms of the underlying disorder are usually very significant: for example, lidocaine was used in a patient with myocardial infarction due to diabetes mellitus and in a patient with chronic hepatitis ; antibiotics - for severe bacterial infections and in a patient with arterial hypertension . Therefore, the pathogenesis of the syndrome can be closely associated with the underlying disease, or an organic disorder of the brain against its background ^[8] .

According to most observations, the syndrome develops immediately after the first injection, according to one of the observations within 60 seconds ^[16] . At the same time, according to a study by Polish psychiatrists, the syndrome develops on average after the 6th injection. The severity of Wanier syndrome does not depend on the dose of the drug and, as a rule, it lasts for a short time (15-30 minutes) ^[2] , although a protracted course of up to several days is possible. The subacute and latent course of the disease is also described ^[17] .

Mental and Neurological Disorders

The first manifestations of the disorder are fear of death and a feeling of helplessness, similar to a panic attack . In the future, agitated psychomotor agitation with confusion occurs, the patient becomes disoriented in place and time, auditory, visual, visceral and olfactory hallucinations develop ^[7] . Possible phenomena of depersonalization and depersonalization ^[18] , the development of paranoid delirium . Using the MMSE test, mild cognitive impairment can be detected due to impaired attention and orientation ^[10] . In one of the described cases, the patient had Kapgra syndrome ^[19] . In addition, generalized tonic-clonic and partial seizures , which are especially common in children, are possible in patients ^[13] .

Somatic disorders

Wanier syndrome is manifested by tachycardia , hypertension, cough , a feeling of constriction in the chest , cyanosis or pallor of the skin, profuse sweating.

According to one of the clinical reviews, laboratory examination methods, including clinical blood analysis , biochemical blood analysis and immunological studies did not reveal any significant deviations ^[10] . According to MRI , multiple subcortical areas were revealed that were hypointensive in T2-weighted images ^[10] .

Differential Diagnosis

Differentiation of Wagnier syndrome is necessary from anaphylactic shock caused by the introduction of the drug, which is characterized by symptoms of angioedema , urticaria , bronchospasm and collapse with arterial hypotension ) ^[2] . With Wanye syndrome, negative provocative and skin allergic diagnostic tests , as well as an oral provocative test for penicillin. The level of specific IgE immunoglobulins remains normal. It is important to conduct differential diagnostics from the point of view of practical medicine due to the fact that further use of the drug is possible with Wagnier syndrome, and it is strictly forbidden with anaphylaxis ^[20] .

Wanier syndrome may also be mistakenly diagnosed as an infectious psychosis proceeding as delirium type, caused by sepsis ^[9] .

Convulsive syndrome due to Wanier syndrome in children can be erroneously diagnosed as epilepsy and subsequently be the cause of improper treatment with the use of anticonvulsants or excessive diagnostic procedures ^[13] .

First aid. First Aid

If Wanier syndrome does not lead to a state of collapse or acute respiratory failure , only the patient’s oxygen supply is used to provide medical care ^[2] . This is due to hypoxia arising against the background of increased metabolism of neurons, which, in turn, can lead to hypercapnia, collapse and seizures. The patient must be reassured, planted or laid in order to minimize damage as a result of psychomotor agitation ^[2] . With severe excitation, it is necessary to prescribe tranquilizers ( diazepam ). Also, for the relief of acute manifestations, it is recommended to administer intravenously drugs from the group of glucocorticoids ( prednisone ) ^[7] .

Rehabilitation

In the process of rehabilitation, observation by a psychiatrist is necessary in connection with the possible development of distant mental disorders with neurotic and psychotic symptoms.

The existing principle of individual and social prevention of the syndrome consists of three provisions ^[13] :

1. Change the injection site regularly.
2. As early as possible transition of the patient to oral administration of penicillins.
3. Producers of prolonged-release penicillins limit the size of the crystals of benzylpenicillin to 20 nm.

Prolonged penicillins cannot be administered subcutaneously , intravenously, intrathecally (directly into the cerebrospinal fluid ) and drip into the body cavity. Injections of benzylpenicillin procaine are recommended to be done in the patient's supine position, which will reduce the risk of impaired injection technology, intramuscularly, in the upper right quadrant of the buttock. It is not recommended to carry out many injections in a limited area ^[7] .

The storage rules for procaine benzylpenicillin must be observed. In particular, it is desirable to store it at a temperature not exceeding 25 ° C due to the fact that storage at room temperature promotes the release of free procaine ^[2] .

Immediately after the Wanier syndrome, patients may develop symptoms of a conversion disorder or hypochondria syndrome ^[21] . A positive correlation was established between the patient's age and the severity of conversion symptoms. According to a study by psychiatrists from Gdansk , all patients after the Wanier syndrome experienced fear of further injections of benzylpenicillin procaine and refused to continue treatment with this drug, and neurotic symptoms were prolonged, with a tendency to relapse and did not respond well to treatment ^[21] .

According to a study conducted in 1994 at the , in 3 patients with Wanier's syndrome, acute exogenous psychosis turned into a state with symptoms of anxious neurosis and in the long term they were diagnosed with acute endogenous psychosis with symptoms of schizophrenia ^{[ 21]} .

British scientists also point to the tendency of Wanier syndrome to chronic in the absence of professional therapy or psychological support. It can be combined with panic attacks, PTSD , phobic disorders and depression of varying severity. The frequency of distribution ( Eng. Observed period prevalence rate ) according to this study was 5.9: 1000 ^[22] .

• Jarisch-Hexheimer Reaction
• Nikolau’s syndrome is a medical embolism of the skin in children after intramuscular injections of penicillin, bismuth or other preparations with a crystalline structure, which manifests itself immediately after the administration of the drug with neurological disorders, ischemia and skin necrosis with the possible development of limb paralysis and other complications ^[23] .