tetanus in iv heroin users

TETANUS IN IV HEROIN USERS Nayyer Iqbal, MRCPsych

Background: Tetanus is a toxic infectious state whose overall incidence is declining. In drug users who inject the drug, the incidence of tetanus may be on the rise. Contaminated heroin is the primary cause. Tetanus among intravenous drug users has been reported worldwide, but there are no such reports from Saudi Arabia. Patients and Methods: Five tetanus cases were diagnosed at our hospital between October 1997 and September 2000. All were intravenous heroin users. Three presented to the outpatient department (OPD) with painful muscle spasms, while the other two were inpatients receiving treatment for heroin withdrawal. The total number of IV heroin users admitted during the same period was 2420 and the number of OPD cases seen was 2973. Results: All had a generalized form of tetanus. Neck stiffness, opisthotonos and painful back spasms were present in every case. Three subjects had trismus and autonomic instability. Two received neuroleptics in hospital as treatment for withdrawals, and one used it to self-medicate. Neuroleptic-induced side effect was the initial diagnosis. Lack of response to anticholinergics and muscle relaxants led to the suspicion of symptoms being due to tetanus. Two cases were misdiagnosed at an early stage by the local emergency service. Conclusion: These cases highlight the importance of the awareness of the possibility of tetanus in IV drug users. Tetanus is a clinical diagnosis. Though still uncommon, the disorder is seen more frequently in some vulnerable groups. Vigilance and a high index of suspicion are required in order not to misdiagnose. Ann Saudi Med 2001;21(5-6):296-299. Key Words: Tetanus, drug users, IV heroin.

Tetanus is a toxic infectious state caused by the bacillus Clostridium tetani.1-6 It is a rare disorder in developed countries, with an incidence rate of one case per million, 3%-10% of these being IV drug users.1,2 The overall incidence of tetanus is declining,7,8 but may be on the increase in injecting drug users. Recent figures from the US show that 11% of the tetanus sufferers were injecting drug users, compared with 3.6% during the early nineties.9 Soil, street dust and intestinal content of animals and humans are the normal habitat of the organism,1-3 but contamination of any wound can result in tetanus. Subcutaneus injection of contaminated heroin (skin popping) is the primary cause in drug users.1,2 Once the organism begins to grow, a powerful exotoxin, tetanospasmin, is produced that is disseminated in the body via blood, lymphatic and retrograde axonal transport along peripheral and sympathetic nerves.1-6 A very small amount of toxin is needed to produce tetanus. This induces a weak antibody response, and immunity is not achieved. Past history, therefore, does not rule out a second attack. Tetanospasmin binds irreversibly with the receptors at the nerve terminals. The mechanism of action is complex From Al Amal Hospital, Jeddah, Saudi Arabia. Address reprint requests and correspondence to Dr. Iqbal: Al Amal Hospital, P.O. Box 7822, Jeddah 21472, Saudi Arabia. Accepted for publication 20 August 2001. Received 20 February 2001.

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and not fully understood.10-12 Classic symptoms result from its effect on spinal and brainstem neurons, where it blocks the release of neurotransmitters GABA and glycine.1-4 The toxin interferes with the functions of the reflex arc by suppressing these inhibitory neurons. There is unrestrained stimulation and sustained muscle contraction. Muscles served by the shortest neural pathways are affected first, e.g., the masseter and cervical muscles. The autonomic nervous system and cerebral cortex are also affected. Rigidity and painful muscle spasms are the main features of the disease.4,6 Mentation remains typically clear unless secondary infection or hypoxia is superimposed. Diagnosis is always clinical.3-6 Tetanus is a toxic state and can be diagnosed in the absence of any cultural proof. Improvement is slow and recovery may take several months. Death is commonly due to respiratory complications,4,6,8 but may also result from direct toxic effect on the tissues. Mortality is highest among the elderly and heroin addicts. Common differential diagnoses include neuroleptic-induced side effects13,14 and strychnine poisoning.15 Conditions like meningitis, rabies, oromandibular disease and conversion disorders may also mimic tetanus,16 especially before it has fully evolved. It can be easily misdiagnosed and dismissed at such an early stage. Generalized tetanus in injecting drug users has been reported from several countries, e.g., US, Spain, Ireland, Germany and Hong Kong.9,17-19 To our knowledge, no such

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reports have been made from Saudi Arabia. Five cases are being presented here for the first time. Case 1 A 32-year-old male IV heroin user was admitted for management of the withdrawal state. He had injected subcutaneously into the foot (inaccessible veins) one day before. Physical examination was unremarkable except for a small swelling on the left sole. He received symptomatic treatment with antipsychotic haloperidol. On the fifth day, he reported stiffness in the jaw and neck that was attributed to the extrapyramidal side effects, and was treated symptomatically with anticholinergic medication (benztropine). There was no improvement in his condition, and by the evening, he was experiencing difficulty opening his mouth. He had severe rigidity of neck and back and complained of intermittent respiratory difficulties. No other physical abnormality was identified. He was alert, oriented, and afebrile, with stable vital signs. Tetanus was suspected and the patient was sent to the local ER, where the diagnosis was dismissed and the patient returned with recommendations for further psychiatric evaluation. On his return, muscle relaxants diazepam and baclofen were prescribed. He continued to deteriorate and 24 hours later had severe trismus with lockjaw, neck stiffness, facial spasms, dysarthria, dysphagia, diplopia, painful spasms in the back, opisthotonos and occasional generalized tetanic convulsions. He was sweating profusely and complained of difficulty breathing. His temperature was normal, pulse 144/min and regular, BP 140/90. He was alert and oriented but extremely fearful of his condition. He was re-referred to the ER for a second opinion and was admitted. Case 2 A 48-year-old IV heroin-dependent male was admitted for the management of withdrawal symptoms. His last injection had been earlier on the same day of admission. He received symptomatic treatment with thioridazine and haloperidol. The next day, he complained of stiffness in the jaw, neck and back. Neuroleptic-induced extrapyramidal side effect was diagnosed. He was prescribed benztropine and diazepam without effect. About 12 hours later, his condition had markedly worsened. He was doubly incontinent, confused and disoriented. On examination, he was afebrile, with a pulse of 138/min and BP of 120/80 (BP had fluctuated during the day between 110/70 and 150/100). He appeared dehydrated and had bilateral basal lung crepitations. Positive neurological findings were trismus with lockjaw, neck stiffness, facial spasms, opisthotonos and painful back spasms. Abnormal investigations were ESR 34, serum Na 132, alkaline phosphatase 199, and GGT 73. Serum strychnine level was negative. The patient was transferred to the local general hospital with the diagnosis of tetanus, where he remained hospitalized for over three months. He returned to IV use immediately after discharge and was readmitted to our

hospital two months later with complaints of insomnia, difficulty in walking, talking and swallowing of one week’s duration. He had discontinued his discharge medication, which he could not name. On examination, the patient had profuse sweating and appeared in discomfort from repeated painful back spasms. He was alert and oriented with stable vital signs. Neurological findings were characterized by generalized increase in tone or rigidity. Trismus, neck stiffness and opisthotonos were present. Leg muscles were extremely rigid and he was unable to walk. He had unsustained clonus in the lower extremities, reflexes were symmetrically brisk and plantar was downgoing. Tetanus was suspected and the patient was transferred to the local ER, where the diagnosis was dismissed. On his return, benztropine and diazepam were prescribed with no effect. He had a fall the next day and sustained blunt head trauma with bleeding from the left ear. Two days later, he developed left facial weakness (LMN type). ENT examination was unremarkable and CT scan of the head was normal. He continued to have rigidity and spasms, and his medication was changed to baclofen. There was slow but complete resolution of symptoms over the next week, and the patient was discharged three weeks after admission. Case 3 A 40-year-old polydrug-dependent male with five previous admissions presented to the OPD. He had relapsed into daily IV heroin use one week previously after several months of abstinence. He complained of neck and back stiffness of one day’s duration, which had gradually worsened. Anticholinergics were prescribed at a private hospital without benefit. On examination he was alert and oriented with stable vital signs. Neck, back and abdominal muscles were rigid. He had intermittent painful back spasms with opisthotonos. There was no response to parenteral benztropine and diazepam. Tetanus was diagnosed and the patient was transferred to the local general hospital. Case 4 A 35-year-old IV heroin-dependent male presented to the OPD with painful spasms affecting back and abdomen of one day’s duration. His last injection was on the morning of admission. He was alert, oriented and appeared very anxious. Vital signs were stable and he was afebrile. The neck was rigid, abdomen was board-like, and he had opisthotonos. There was no history of phenothiazine use. Parenteral benztropine and diazepam were ineffective. Tetanus was diagnosed and the patient was transferred to the general hospital. Case 5 A 40-year-old IV heroin user presented for admission to the OPD. He had relapsed two weeks earlier after six months of abstinence. He was injecting daily and his last


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injection had been a day earlier. He reported being unwell for the previous three days. He was alert, oriented and sweating profusely. Neurological findings were trismus, dysarthria, dysphagia, neck stiffness, opisthotonos and painful back spasms. Vital signs were stable and he was afebrile. There was a history of self-medication with phenothiazines (thioridazine) two days before. Parenteral anticholinergic (benztropine) was prescribed with no effect. Tetanus was diagnosed and the patient was transferred to the general hospital. Discussion Effective immunization programs, good health care and better living conditions have almost eliminated tetanus from some parts of the world.1-3 Despite being a rare disease, it is still encountered in vulnerable groups like intravenous drug users, as the above cases demonstrate. All had generalized tetanus. The cases reported in the literature also suffered from a generalized form of the disease. Since our cases were managed at other hospitals, the mortality and morbidity is not known, however, two of the five cases were subsequently seen in the OPD with no neurological deficits. The fate of the other three is not known. Conditions like neuroleptic-induced side effects and strychnine toxicity produce symptoms closely resembling tetanus. In drug users, this makes diagnosing tetanus more difficult. Street heroin is adulterated with substances like strychnine,15 phenothiazines, benzodiazepine, barbiturates, etc. Abuse of multiple drugs, including phenothiazines, is not uncommon and many addicts either self-medicate or receive these medications privately for control of withdrawals. Neuroleptics or major tranquilizers are sometimes prescribed to treat mild withdrawal symptoms. The above cases received these medications for this reason. Neuroleptic-induced side effect was the provisional diagnosis in all cases. Strychnine poisoning is a rare condition and was suspected in only one case. Negative serum levels excluded this. It was lack of response to anticholinergics and muscle relaxants that led to the possibility of the symptoms being due to tetanus. This was substantiated further by classical clinical findings. It was not surprising that two cases were sent away at the early stage by the ER. The diagnosis was never in doubt once the condition had fully evolved. Neck stiffness, opisthotonos and spasms in the back were the most consistent findings in every case. Trismus, the hallmark of tetanus, was present in three cases. Mentation was clear in all except one case, in whom confusion and disorientation was most likely due to infective metabolic causes. Complications like aspiration, pneumonia, etc., are common in tetanus and this case had chest findings suggestive of this. Breathing difficulties in the other two cases were most probably due to spasms and splinting of the chest wall muscles. Autonomic nervous

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system involvement occurred in three cases. This was manifested by heart rate changes, variability in blood pressure and increased sweating. Case 2 was readmitted after five months with recurrence of tetanus symptoms. Rigidity was a prominent feature. It was interesting that facial nerve palsy evolved after the patient had a fall. This was most probably a symptom of generalized form of tetanus, as ENT exam and CT scan of the head were both normal. Although reinfection was a possibility, as this patient started injecting soon after discharge, persistence of the symptoms from the original event was more likely as a diminution in rigidity in tetanus is known to be slow and may take months to clear. Clear mentation, afebrile course and absence of headache made meningitis an unlikely possibility. Oromandibular disease was excluded by lack of history and physical findings. Conversion disorder was improbable. This is mostly seen in young females. Gait disturbance, motor weakness, convulsions and aphonia are the main symptoms. The condition does not conform to any known neurological disorder or neural pathways. Despite the severity of the symptoms, these individuals show little concern or distress. None of these was present in the above cases. Animal bite was not reported in any of the cases, therefore rabies was not a possibility. Trauma is often not recalled by most tetanus sufferers. It could be minor and easily forgotten. However, all subjects were injecting heroin, and contaminated heroin (not dirty needles, as is commonly believed) is a known cause of tetanus. Heroin may get contaminated during injection preparation or in transit (clandestine methods used by the traffickers, e.g., heroin hidden inside body cavities of humans or animals). The total number of IV heroin users admitted during the study period (October 1997 to September 2000) was 2420. Five cases of tetanus were seen during the same period at our hospital, which specializes in addiction treatment, giving an inpatient incidence rate of 0.08% or 8 cases per 10,000. The number of OPD cases for the same period was 2973 with an incidence of 0.10%, or 10 cases per 10,000 IV heroin users. Nowadays, the disorder is more frequently seen in this group. The actual incidence rate is probably much higher, as milder forms of the disease presenting only with rigidity could be mistaken for extrapyramidal side effects and easily missed. Tetanus is a clinical diagnosis. As these cases show, it is important to promptly and correctly recognize the disease. Injecting drug users are particularly at risk. Vigilance and a high index of suspicion are required in order not to misdiagnose. Acknowledgements I wish to thank Dr. Mohammed Farag, Psychiatric Specialist, Dr. Emad Bedawi, Resident Psychiatrist, and Mr. Abdul Tawab of the Medical Records Department for

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