For citation: Olexenko L.V., Vybornykh D.E. Somatogenic psychoses in Hodgkin's lymphoma. “Pychicheskie rasstroistva v obshchei meditsine" (Mental Disorders in General Medicine) 2017; 01-02: 19-23
Somatogenic psychoses in Hodgkin's lymphoma
National Research Center for Hematology, Moscow, Russian Federation
23 patients were studied with Hodgkin's lymphoma who had somatogenic psychoses. Among the latter, delirium, endogenomorfic psychoses (hallucinatory-delusional, depressive-delirious, oneiroid), somatogenically provoked attacks of schizophrenia are distinguished. A psychopharmacotherapeutic approach to the treatment of the described psychopathological disorders is suggested.
Key words: Hodgkin’s lymphoma, delirium, endogenomorfic psychoses, schizophrenia, therapy.
Descriptions of somatogenic psychoses that manifest in patients who suffer from Hodgkin-LH lymphoma (Hodgkin's disease, lymphogranulomatosis) are few and are presented either in casuistic observations or included in the characteristics of samples of patients with other oncological / oncohematological nosologies. At the same time, the main body of data on such psychoses comes in the middle of the last century, when in the practice of practice, the nitrogen of mustard and procarbazine became (a drug with a weak inhibitory effect on the activity of monoamine oxidase).
With the advent of later generations in the daily practice of hematologists: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone)  - and the possibility of accompanying treatment the severity of the manifestations of psychoses decreased1, but the relevance of the study of such conditions persists. Among the psychotic disorders that manifest in patients with LH, affective, delusional states, delirious confusion of consciousness are described [2-16].
Affective psychoses in patients with LH are represented by psychopathological disorders as manic [2, 6-8], and depressive  pole. It is emphasized that such disorders often develop against the backdrop of chemotherapy. Observations are given in which psychoses occur when nitrogenous nitrite compounds are used, in which, in addition to the state of euphoria, confusion was often observed . In addition, when treating procarbazine, a psychotic mania was noted [6, 7]. At the same time, the presence of the same procarbazine in the polychemotherapy regimen (Mustargen, Vincristine, procarbazine and prednisolone - MOPP) was not an obstacle to the development of psychosis of depressive content in another observation .
Psychological disorders of the delusional register are presented by depressive-delusional and hallucinatory-delusional conditions. Authors describing such psychoses indicate the possibility of their manifestation both outside the course of chemotherapy , and against chemotherapy with compounds of nitrogen mustard . Researchers noted that after the cessation of therapy with nitrogen syring, manifestations of psychosis relatively quickly stopped . Often, the structure of the described states revealed catatonic disorders. In addition, the development of psychoses of depressive-delusional and hallucinatory-delusional content in patients with LH manifesting against corticosteroid therapy is described [10-12].
B.A. Tselibeev et al. (1964) published 2 observations of somatogenic psychoses in patients with LH.
In one case, poisoning was noted, in another - psychomotor agitation with fragmentary delirious ideas, auditory and visual hallucinations during periods of deterioration of the somatic state .
D.Vybornykh (2012) cites a clinical description of a patient suffering from drugs in whom a recurrence of the disease of the blood system coincides with a hallucinatory-delusional attack with the Kandida- sko-Clerambo syndrome and catatonia in the framework of a schuboid (paroxysmally-progredited) schizophrenia  ,
In a study conducted in 2014, it was shown that a significantly higher proportion of psychoses of the schizophrenic spectrum (endogenomorphic psychoses - hallucinatory-delusional and depressive-delirious states and schizophrenia attacks), revealed in lymphoproliferative diseases, especially lymphosarcomas and LH. And in the case of LH, these forms of somatogenic psychosis occur much more often than delirium, unlike other diseases of the blood system. In addition, in this course, LH was the only disease in the blood system, in which somatogenically induced schizophrenia attacks were identified .
The delirious and oniroid obscuration of consciousness observed in patients with LH is generally comparable to similar psychoses that manifest in other severe somatic diseases [4, 16].
Thus, there is a tendency towards the prevalence of psychopathological disorders of the endogenous circle (the presence of catatonic disorders in their structure), as well as affective disorders predominantly of the manic pole. In addition, in most cases, psychoses manifest on the background of aggressive chemotherapy of the underlying disease.
Material and methods
The study was conducted on the basis of the clinical departments of the FGBU SSC. The clinical examination procedure included analysis of the mental state, subjective and objective anamnestic information, including medical records (current and archival medical records, hospital records, outpatient cards). Psychopathological evaluation was carried out by the authors of the study. Hematologic examination in addition to standard physical examination included evaluation of blood parameters and (if necessary) bone marrow, morphological structure of hematopoietic and lymphoid tissue (bone marrow puncture and bone marrow biopsy), ultrasound examination of the abdominal cavity, various specialized studies (immunochemical, etc.) with final expert opinion as a result of clinical analysis with the participation of managers and researchers of the clinical departments of the FGBU SSC. The sample of the study was formed for the period from April 20, 2015 to March 31, 2017 from the number of patients with a verified diagnosis of blood system diseases hospitalized in the clinical departments of FGBU SSC, who had somatogenic psychoses. Included were all patients with LH who developed somatogenic psychoses. Only patients with an extremely difficult physical condition who were not allowed to perform a psychopathological examination in the volume necessary for evaluation were excluded. The sample consisted of 23 patients (women 30.4%, men 69.6%, ages 22 to 69, mean age 37.52 ± 11.14 years) suffering from LH. The duration of the disease from the date of detection of the disease of the blood system varied from 0.6 to 6.8 years (an average of 1.9 years).
The results of this study support the hypothesis formulated on the basis of literature analysis of the clinical heterogeneity of somatogenic psychoses that form in patients with LH. Differences in the psychopathological manifestations and dynamics of the studied conditions in accordance with the typology developed in the studies of the laboratory for studying mental and neurological disorders in diseases of the blood system of FGBU SSC performed on a sample of patients of the hematological clinic  allowed to identify 3 types of somatogenic psychoses:
1) delirium (F05.0), traditionally attributed to reactions of exogenous type ;
2) endogenomorphic psychoses - organic delusional (schizophreniform) disorder (F06.2), psychotic states manifesting in the mechanisms of somatogenies, but differing in significant polymorphism and atypia of the symptomatology, including psycho-pathological disturbances of the endogenous circle not characteristic for exogenous psychoses (hallucinatory-delusional, depressive-delirious, onyroid syndromes);
3) somatogenically provoked exacerbations of schizophrenia - paranoid schizophrenia, paroxysmal course (F20.01); Table. 1. Somatogenic psychoses in Hodgkin's lymphoma
Somatogenic psychoses in Hodgkin's lymphoma
Table 1.Typology of somatogenic psychoses in Hodgkin's lymphoma
The first type is Delirium, 4 (14.3%) out of 23 observations. The clinical picture as a whole is comparable with delirious states in other severe somatic diseases [15, 18] and includes the phenomena of obscuration of consciousness with complete or partial disorientation in the surrounding, the influx of visual hallucinations, acute sensory (hallucinatory) delirium, motor excitement. In a series of affective disorders, a sense of anxiety, fear with phenomena of confusion prevailed.
The severity of disorders of consciousness and other psychopathological disorders varies within a day. If in the first half of the day there is somnolence or stunning with motor retardation, partial disorientation in place and time, by evening, and especially in the first half of the night, there is an aggravation of the phenomena of confusion of consciousness, hallucinatory and delusional disorders with the development of psychomotor agitation.
At the conclusion of psychosis (psychopathological disorders were reduced as the somatic state improved), signs of retrograde amnesia with a complete loss of memories associated with symptoms of delirium were revealed. During 5-7 days after the reduction of psychopathological symptoms, the mood was unstable with a propensity for depression, as well as asthenia with increased fatigue, rapid exhaustion with minimal physical or mental stress, capriciousness and resentment.
It should be emphasized that in the patients studied delirious disorders are mostly erased in nature, and the confusion of consciousness occurs with pronounced asthenic and apathetic disorders. This rudimentary form of delirious unconsciousness, in which psychomotor excitation is either absent or not expressed, was found in the majority of delirious patients - 3 (13.0%) of 23 patients.
The clinical picture is dominated by the phenomena of irritable weakness, short-term episodes of increased excitability, followed by long periods of exhaustion. Identified affective lability with a predominance of hypothyroidism, while depression with increased tearfulness alternated with apathy or elements of dysphoria. In some cases, the phenomena of asthenic mentism with a stream of figurative representations were noted. The function of attention was sharply upset, and then the violations of orientation in time and space were manifested.
Deployed (hypoactive) delirium (with a predominance of perception deceptions and psychomotor agitation) [19, 20] was diagnosed in one observation. Somatogenic psychosis was characterized by adherence to the phenomena of mental confusion of perception deceptions (true - visual, auditory or tactile hallucinations). At the same time, their everyday content (events in the clinic or in the family) was periodically replaced by visions of the invasion of our planet by foreign civilizations, which brought such disorders closer together with a fantastic delirium . However, hallucinatory disorders remained fragmentary and intensified in the evening. Such violations were accompanied by psychomotor excitement, limited to the outside of the bed.
The duration of the delirium averaged 4.7 ± 0.6 days. At the end of the psychosis within 2-3 weeks, the patients reported asthenic disorders.
In the history of patients who suffered a delirious disorder of consciousness, long-term alcohol abuse, episodes of metal psychosis, repeated calls for specialized help to narcologists were detected.
The second type - endogenomorphic psychoses - 11 (47,8%) observations. The duration of such psychoses was 7-11 days. In the clinical picture of psychoses, changes in consciousness, deceptions of perception, as well as psychopathological disorders characteristic of hallucinatory-paranoid, depressive-delirious states and onyroid occultation of consciousness were combined.
Hallucinatory-paranoid states, which account for more than one-third of all identified psychoses in the sample studied-5 (21.7%) out of 23 observations, are manifested by verbal illusions like acoasms (hiss, squeaks) or elementary functional hallucinations (addressed to the patient individual words or phrases arising on the background of noise of medical equipment or the speech of personnel).
Subsequently, these perceptual disorders gradually become more complicated with the formation of verbal pseudo-hallucinations and the phenomena of mental automatism (ideas of influence with the help of medical equipment) with the development of ideas of persecution corresponding to their content. In this case, it should be noted a relatively small scale of delusional disorders, which were limited to little-systematized ideas of the relationship. The patients attached special importance to the manipulations of medical personnel, "noticed" that doctors somehow whisper in their presence in a special way, or something is kept secret, probably to hide the consequences of their "mistakes". Against the backdrop of the dominance of the notion of "bias" of medical personnel, in some cases the ideas of a "conspiracy" of small scope are revealed. So, the patients claimed that the doctors conduct "experiments" over them, "test" questionable medications, etc.
Endogenomorfnye psychoses in the type of depressive-delusional conditions were revealed in 2 (8.7% of all psychoses) observations. Psychoses of this type were manifested with hypothyroidism with an anxious affect, reaching a maximum in the evening hours.
In patients at night, there was a development of deceptions in the form of true hypnagogic visual hallucinations, which had an elementary character. Depressive disorders acquired a vital character with a sense of anguish, helplessness, ideas of self-blame and even suicidal thoughts. As the anxious and dreary affect intensified, paranoid disorders, represented by persecutory delusions (ideas of attitude, persecution) were added, the latter was distinguished by the monotheism of the plot, not revealing the trend towards systematization, and limited to ideas of prejudice and condemnation from others (medical personnel, patients).
In most cases, the duration of hallucinatory-paranoid and depressive-delirious states was less than 2 weeks. In the process of the reverse dynamics of psychosis, the reduction of psychopathological symptoms acquired a certain sequence associated with the somatogenic nature of the disorder: first, the delusional and hallucinatory disorders were reversed, then depressive manifestations and asthenic symptoms.
In 4 (17.4%) cases out of 35, the clinical picture of somatogenic psychoses corresponded to the onyeroid obscuration of consciousness . The development of the onyroid in our observations was preceded by disorders that lasted for several hours, which were similar to the "delusional mood", combined with affective disorders of the manic pole and asthenic disorders. Patients suddenly had a feeling of unreasonable excitement, expectations for something unusual, joyful. Events taking place in the clinic acquired a hidden meaning. The affective tension with the elements of sensual delirium suddenly grew into an onyroid obscuration of consciousness with the phenomena of double orientation in one's own personality. Patients simultaneously acted as patients of the clinic and external observers. On examination, they were confused, looked around in bewilderment, their eyes slid from one subject to another. The scene-like hallucinatory disorders that were formed in this case were characterized (in contrast to the fantastically illusory pictures typical of the "classical" onyroid psychoses ) with ordinary content. The patients told about what they thought, "as if they were sleeping and not sleeping." The duration of the onyroid was limited to one or two short episodes, marked for one day or several nights. Catatonic inclusions were manifested by elements of motor awkwardness, separate stereotypes, short freezings. Along with the onyeroid-catatonic manifestations, fragmentary persecutions were revealed.
In a history of patients with endogenomorfic psychoses, psychiatric disorders were triggered, provoked by external events, over which some patients sought help from psychiatrists. Hospitalizations in psychiatric hospitals are not registered.
The states qualified in this study within the framework of endogenomorfic psychoses show a number of differences from similar disorders of the endogenous-procedural circle. These include the appearing in the clinical picture of the phenomenon of asthenia with tearfulness and exhaustion of affect, and not the fences and indifference inherent in patients with schizophrenia. Other distinguishing features are the variability of behavior and affect lacking monotony, the somatogenic nature of the dominant asthenic disorders that are not displaced by hallucinatory-delirious or depressive-delirious symptoms. In addition, there is a difference in the psychopathological characteristics of delusional disorders, devoid of a tendency to a pronounced systematization, an expansion of the plot and a transition to a chronic course. The final (after completion of psychosis) diagnostic judgment is reduced to the statement of absence of personality changes, as well as emotional or cognitive deficits.
The third type - somatogenically provoked attacks of schizophrenia - 8 (34,8%) of 23 observations. In all patients, seizures occurred with the detection of a hallucinatory-paranoid syndrome.
The psychopathological structure of psychosis was determined by the combination of a process-mediated and somatogenic pathology. Along with the symptoms inherent in somatogenic psychoses (confusion of consciousness with disorientation in place and time, psychomotor agitation, diurnal fluctuations with intensification in the evening and at night), already in the debut of psychosis, the psychopathological disorders inherent in endogenous-procedural disease were revealed. In the future, as the somatic state of the patient normalizes with the reverse development of disorders of consciousness and other somatogenic disorders, the manifestations of psychosis are not reduced, but acquire a syndromic completeness. Improvement of the somatic state is accompanied by the crystallization of delirium (the impact on the thoughts and actions of the staff, including with the help of medical equipment), the change of intimidating visual hallucinations with verbal pseudo-hallucinations. The hallucinatory-delusional symptomatology is combined with aggression and attempts of physical violence against "persecutors" - medical workers, neighbors in the ward.
In cases of somatogenically provoked attacks of schizophrenia, endogenous psychosis acquires a protracted course; remission is formed only after 2,5-3 months even in conditions of adequate therapy.
It should be emphasized that the psychoses that we attributed to somatogenically provoked schizophrenia episodes are comparable in manifestations with psychotic attacks revealed in the anamnesis of patients and requiring in 2 observations of inpatient treatment in a psychiatric clinic. The duration of the endogenous process averaged 8.3 ± 3.6 years.
Therapy of the described psychopathological disorders was carried out in two stages. The goal of stage I was the relief of psychosis, II - maintenance treatment aimed at preventing the recurrence of a psychotic disorder.
With delirious disorders of consciousness, the main volume of therapeutic intervention was concentrated at the first stage; treatment is short-lived and includes the use of antipsychotic butyrophenone series (haloperidol up to 15 mg / day). If necessary, rapid sedation or relief of anxiety / insomniac disorders in the therapeutic regimen was administered diazepam (up to 20 mg / day).
The therapy of endogenous psychosis required more intensive effects (daily doses of antipsychotics increased: haloperidol up to 20-30 mg) and longer duration (up to 2 weeks). At the second stage of treatment of endogenomorfic psychoses, the dosages of the psychotropic drugs used were reduced (haloperidol up to 5 mg / day, Rispolept - 2 mg / day).
The most prolonged (up to 1.5-2 months) treatment with the use indicated in Table. 2 maximal dosages of drugs required somatogenically provoked attacks of schizophrenia. At the same time, the appointments were adjusted in accordance with the dynamics of the somatic pathology (the doses decreased with weighting of the somatic state).
Clinically significant side effects during therapy with the psychotropic drugs used or their adverse interactions with somatotropic drugs, including corticosteroids (prednisolone) and cytotoxic agents (doxorubicin, bleomycin, vinblastine, vincristine, dacarbazine, etoposide, cyclophosphamide, procarbazine) were not observed.
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