In the clinical case we have described it was not easy to establish the diagnosis at the stage of initial medical and physical examination. The patient's multiple morbidity and mental state made it impossible to obtain precise information on the events preceding the current illness. The symptoms presented by the patient, such as fever, tachycardia, tachypnoe, leukopenia and hypocapnia in blood gasometry, met the criteria of the SIRS. It most often develops as a result of severe bacterial, viral and fungal infections, less often under the influence of mechanical injuries, prolonged surgical procedures, burns, pancreatitis, heat stroke as well as under the influence of chemicals, including drugs. SIRS symptoms are the result of excessive release of pro-inflammatory cytokines (TNF-a, Il-1, IL-6), acting locally and systemically. These are responsible, among others for the increase in temperature and the synthesis of acute phase proteins (CRP, PCT, fibrinogen) [5]. As is known, PCT and CRP are important biomarkers of bacterial sepsis, so identifying SIRS from a cause other than sepsis at the initial diagnostic stage is a difficult task, as we experienced in our case as well. Procalcitonin, like the CRP participates not only in the non-specific response of the organism to infectious stimuli, but its concentration increases, among others in extensive tissue damage during injuries, surgery and burns, in acute pancreatitis, and myocardial necrosis [6,7,8,9]. Under physiological conditions PCT is an intermediate product of the synthesis calcitonin produced by the thyroid gland in C cells, CRP is produced by hepatocytes in trace amounts. CRP determined in the low range of its concentrations by methods of high analytical sensitivity (hsCRP) reflects low grade inflammation, which is attributed to a significant role in the pathogenesis of atherosclerosis. The usefulness of the hsCRP test was also demonstrated in addicted adults in the 18–48 age group, finding significantly higher hs-CRP in the addicted group as compared to healthy controls. Therefore, it has been suggested that chronic opiate abuse leads to constant stimulation of atherogenesis with the participation of CRP, which takes part in all stages of formation, remodeling and destruction of atherosclerotic plaques, resulting in many health consequences described in drug addicts [10]. As mentioned above, an increased concentration of CRP was also found in our patient during the outpatient control, probably resulting from constant drug abuse, but also probably from disturbed energy homeostasis in the patient, as evidenced by: increased body mass index (BMI) (25.6 kg/m2), significantly exceeding the norm, high serum concentration of triglycerides and low level of high-density lipoprotein (HDL) cholesterol. All these abnormalities may be a significant factor in cardiovascular events in this patient.
Due to the symptoms presented at admission, such as fever, vomiting, headaches, and very high inflammatory parameters, the presence of CNS infection was considered as the cause of the disorders. However, due to the lack of any abnormalities in the neurological examination, the suspicion of intoxication with psychoactive substances, and then a quick improvement of the general condition with a dynamic decrease in inflammatory parameters, lumbar puncture and brain imaging were finally abandoned.
The symptoms of tachycardia, fever, tachypnoe, nausea, vomiting, limb muscle tremors, dryness of mucous membranes and skin, described on admission, were the symptoms of intravenous administration of a large dose of amphetamine, responsible for the stimulation of the sympathetic part of the autonomic nervous system. On the other hand, no symptoms typical of amphetamine poisoning, such as pupil dilation, blood pressure increase, psychomotor agitation, panic attacks, were observed. Perhaps this was due to the simultaneous intake of morphine, which has an antagonistic effect in relation to amphetamines. It stimulates the parasympathetic autonomic nervous system, especially its centers in the brain and spine. It has a euphoric effect, causes drowsiness up to coma, respiratory disorders up to apnea, bradycardia, hypotension, arrhythmias and impaired conduction of the heart stimulus system, urinary retention, pupil constriction [11, 12]. There are case reports [13,14,15,16,17] of extremely high levels of inflammatory markers (PCT levels up to a thousand times the normal limit) without concomitant bacterial infection in adult drug addicts after an overdose of amphetamines and opioids. In these patients, apart from hyperthermia and tachycardia, significant psychomotor agitation requiring administration of high doses of neuroleptic and antipsychotic drugs was observed, which resulted in respiratory disturbances and the need to introduce emergency breathing. In addition, transient hepatic dysfunction, rhabdomyolysis and acute kidney injury have been reported. In our patient, kidney tests, muscle and cardiac enzymes levels were normal, only a temporary increase in transaminases was observed. As in the described cases, after the exclusion of bacterial infection, antibiotic therapy was abandoned after 4 days.
In people using psychoactive substances, disorders in the immune system are also observed, which predispose to recurrent infections. Few studies showed a significant increase in serum IgA, IgM, IgG or IgG3, IgG4 concentration and the elevation of percentage of B lymphocytes subpopulation, lymphopenia and monocytosis in a group of addicted young people, similarly to our patient [18, 19]. As mentioned, the patient was diagnosed with bipolar disorder. It is believed that imbalances between pro and anti-inflammatory cytokines play a role in the pathogenesis of the disease. High levels of pro-inflammatory cytokines Il-6, TNF alpha, C-reactive protein, especially during the manic episode, and to a lesser extent in the depressive phase, have been documented [19]. Incresed values of NLR and PLR are considered to be an indicator of increased inflammation. NLR and PLR indices were found to be elevated in heroin dependence and psychiatric disorders such as schizophrenia, bipolar disorder and depression [20]. High values of NLR and PLR were found also in our patient upon admission—several hours after intravenous amphetamine intake. They were gradually reduced in the following days of hospitalization, but they were higher than values observed in healthy adolescents at the same age group [19]. Next control laboratory tests performed one month after the initial hospitalization showed a re-increase of these indicators, which could be attributed to the continuous use of psychoactive substances. Additionally, the patient was confirmed with significant hypovitaminosis D (9.99 ng / ml), which, according to the literature, may be associated with mood disorders, depression and bipolar disorder [21, 22]. In addition, low vitamin D3 levels are a predictor of suicide attempts. Determination of the concentration of Vit D3 and treatment of its possible deficiency may therefore be beneficial in the treatment of depressive disorders [23]
In the absence of one recommended single standard of care in patients abusing drugs in the event of the appearance of high levels of acute –phase proteins, the only legitimate way to proceed is the exclusion of the other possible causes of this increase, such as infection, in particular sepsis, psychiatric disorders, and others. The only gold standard for dealing with an acute patient after intoxication with psychoactive substance is a detailed interview, thorough examination, and diagnosis by exclusion of the organic causes of this condition.
Since infections were excluded and the other comorbidities like bipolar disorder and allergic disease were well controlled, the elevation of acute phase proteins along with clinical signs, of methamphetamine use—like fever, tachycardia, dry skin—and the decrease in those levels after cessation of methamphetamine use suggested that the elevation of acute phase proteins was probably due to drug abuse.
The discussed case displays the difficulties of differential diagnosis in a teenage patient struggling with many diseases, who has been abusing drugs for several years, remains in an ineffective family care system, which results in the lack of effectiveness of the undertaken therapies and further destruction of the girl’s health condition, both in the mental and somatic aspects. Increased inflammatory parameters described by the rise in PCT, CRP, NLR, PLR may be caused by many factors. In adolescents who frequently experiment with psychoactive substances, such cause of the increase of these parameters should also be taken into account.
