Fever and haemoptysis in an injecting drug user
BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e1568 (Published 13 March 2012) Cite this as: BMJ 2012;344:e1568
- Vishal Luther, core medical trainee year 21,
- Jennifer Townell, core psychiatry trainee year 32,
- Haseeb Rahman, foundation year 2 doctor1,
- Chee Yee Loong, consultant cardiologist1
- Correspondence to: V Luther vishal_luther{at}yahoo.co.uk
A 24 year old man presented with a 10 day history of fever, night sweats, weight loss, and a productive cough with occasional haemoptysis. He had a history of injecting drug use. He was on a community methadone replacement programme for opiate dependency. On examination, he had a fever (39.4°C), hypotension, and tachycardia. He had a few needle track marks in both antecubital fossae. Coarse crackles were heard throughout both lung fields, although oxygen saturation was 97% on room air.
Blood tests showed: white cell count 19.8×109/L (reference range 4-11), C reactive protein 186 mg/L (<10), urea 15.5 mmol/L (2.5-6.7), and creatinine 210 μmol/L (70-100). Urine dipstick was positive for blood.
Plain chest radiography showed multiple, round, ill defined areas of consolidation throughout both lung fields, with loss of the cardiac silhouette at both the right and left heart borders, as well as bilateral blunting of both costophrenic angles to the lower zones. No hilar or mediastinal lymphadenopathy was noted. He was started empirically on intravenous benzylpenicillin and oral clarithromycin for presumed severe community acquired pneumonia (as per local hospital guidance). His methadone prescription was confirmed with community drug services and the dose corrected for his renal function. Sputum culture was unremarkable and was negative for acid and alcohol fast bacilli. Serology for HIV and autoantibodies was negative. Two consecutive blood cultures grew Staphylococcus aureus.
Questions
1 What is your differential diagnosis from the history and examination alone?
2 Which single investigation would you request to confirm the main cause?
3 What acute medical complications are associated with injecting drug use?
4 How would you manage opiate dependency in the acute medical setting?
Answers
1 What is your differential diagnosis from the history and examination alone?
Short answer
Acute constitutional symptoms with cough and haemoptysis suggest an acute infection of the respiratory system, probably community acquired pneumonia from a typical or atypical micro-organism. The history of injecting drug use increases the risk of HIV and associated opportunistic infections, such as Pneumocystis jiroveci pneumonia or tuberculosis.
Long answer
The combination of fever, night sweats, and weight loss suggests an active inflammatory process. This may be infective, malignant, or autoimmune. Cough and haemoptysis suggest a respiratory source or involvement. The rapid onset of symptoms reduces the likelihood of cancer. Differential diagnoses to consider are:
Community acquired pneumonia: The most common micro-organism is Streptococcus pneumoniae. Although all ages can be affected, it is most prevalent in patients over 65 years, in addition to those with chronic disease and immunosuppression—these groups are routinely offered the pneumococcal vaccine. Pneumonia as a result of S aureus is more common after influenza in older patients and is also classically associated with injecting drug users, manifesting radiologically as bilateral cavitating lesions.1
Atypical pneumonias: Examples are pneumonia caused by Mycoplasma pneumoniae or Legionella pneumophila, which is associated with a multisystem involvement and a dry cough. Mycoplasma is associated with erythema multiforme.2 Legionella is associated with hot water systems and air conditioning, and it may be accompanied by impaired liver or renal function, as well as hyponatraemia secondary to the syndrome of inappropriate antidiuretic hormone release.3 4
HIV associated respiratory infections: These include tuberculosis and P jiroveci pneumonia. The patient’s history of injecting drug use puts him at risk of contracting HIV. Tuberculosis can be identified by examining early morning sputum or bronchoalveolar washings for acid and alcohol fast bacilli (which resist decolorisation with Ziehl-Neelsen staining).5 P jiroveci can be identified by microscopic staining or by polymerase chain reaction assays from induced sputum or bronchoalveolar lavage.
Pulmonary-renal syndromes: Examples are Wegener’s granulomatosis and Goodpasture’s disease. These present with the combination of haemoptysis and renal failure (rapidly progressive glomerulonephritis). Goodpasture’s disease is often seen in young men and is caused by antiglomerular basement membrane antibodies binding to type IV collagen in both alveolar and glomerular basement membranes. Wegener’s granulomatosis is an antineutrophil cytoplasmic antibody associated small vessel vasculitis, characterised by necrotising granulomatous inflammation. In addition to alveolar and renal involvement, the upper airways are often affected, and this can lead to sinusitis and destruction of the nasal septum.6
2 Which single investigation would you request to confirm the main cause?
Short answer
In the setting of S aureus sepsis in an injecting drug user, the radiological signs (fig 1⇓) suggest the possibility of septic emboli from right sided endocarditis, and echocardiography should be performed as soon as possible (fig 2⇓).
Fig 1 Plain chest radiograph showing multiple irregularly defined patches of consolidation (arrows) distributed throughout both lung fields, with loss of the cardiac silhouette at both the right and left heart borders, as well as bilateral blunting of both costophrenic angles to the lower zones
Fig 2 Transthoracic apical four chamber echo window showing a 2.8 cm vegetation (red arrow) seated on the inferior edge of the tricuspid valve, extending into the mid RV cavity in early systole
Long answer
S aureus can enter the venous circulation after the use of a non-sterile intravenous needle in illicit drug users. This micro-organism can subsequently travel to the right side of the heart and infect the tricuspid valve, leading to infective endocarditis. S aureus is now the most common cause of infective endocarditis in many parts of the developed world.7 The presence of bilateral lung consolidation in an injecting drug user with S aureus sepsis is almost diagnostic of septic embolisation from an underlying infected tricuspid valve.8 Thus, an echocardiogram should be urgently undertaken. Transthoracic echocardiography is quick and easy to perform in most hospital settings and should be undertaken within 24 hours for all patients with suspected infective endocarditis. However, its sensitivity for detecting signs of infective endocarditis is only 40-63%, whereas the sensitivity of transoesophageal echocardiography ranges from 90% to 100%. This test should be performed if transthoracic echocardiography is of poor quality or negative and the clinical suspicion remains high. Transoesophageal echocardiography is not mandatory in isolated right sided native valve infective endocarditis with good quality transthoracic echocardiography results and an unequivocal finding on echocardiography.9
The diagnosis of infective endocarditis follows the Dukes’s major and minor criteria.10 Major criteria are the presence of at least two consecutive positive blood cultures for micro-organisms typically associated with infective endocarditis (such as the viridans streptococci group or S aureus) and echocardiographic evidence of new valvular regurgitation, valvular vegetation, or abscess. Minor criteria include a predisposing factor such as injecting drug use, fever (>38°C), positive blood cultures that fail to meet the major criterion, evidence of immune complex mediated vasculitis (for example, microscopic haematuria), and septic emboli. Infective endocarditis is diagnosed in the presence of two major, one major and three minor, or all five minor criteria.
Patients with confirmed endocarditis require inpatient treatment with active cardiology and microbiology input. Most patients will need prolonged intravenous antibiotics, guided by culture results if available. Review patients regularly for symptoms and signs of ongoing sepsis and embolic phenomena with the aid of inflammatory markers, urinalysis, blood cultures, and electrocardiography. Consider surgical intervention for right sided endocarditis in patients with uncontrolled local infection or severe tricuspid regurgitation with refractory right heart failure.11 A conservative approach is generally favoured because the prognosis of right sided endocarditis is relatively good, with an in-hospital mortality rate of 10%.12
3 What acute medical complications are associated with injecting drug use?
Short answer
Injecting drug users can present with local and systemic infections; venous thromboembolism; complications from HIV, hepatitis B, or hepatitis C; overdose; and opiate withdrawal. Management is often complicated by their drug dependency and concomitant psychosocial circumstances.
Long answer
Injecting drug use is associated with local and systemic medical complications,13 often through the introduction of infectious agents and other contaminants into the body via shared needles and a lack of sterile preparation. Common bacterial micro-organisms include staphylococci, streptococci, and clostridia. Cutaneous infections range from cellulitis and localised abscesses through to necrotising fasciitis. These infections can spread systemically and lead to infections or abscess formation in multiple sites. Bloodborne viruses, including HIV, hepatitis B, and hepatitis C, are often spread via needle sharing. Injecting drug use is responsible for about 60% of HCV infections in the United States.14 Injecting drug users are at high risk of sexually transmitted infections because they often engage in high risk sexual activity (such as prostitution) and are not compliant with barrier contraception.
Chronic venous injection with drugs and other additives predisposes patients to deep vein thrombosis, and management of these patients is often complicated by a lack of adherence to treatment and monitoring, as well as potential pharmacological interactions between street drugs and anticoagulants.15
Illicit drugs have various sequelae in overdose. Heroin overdose can cause marked respiratory depression and death.16 It is often a challenge to identify the illicit substance and the correct antidote on acute presentation.
Patients who are dependent on opiates may experience withdrawal symptoms as little as four hours after their last dose of heroin. They may become aggressive or even abscond, so it is important to manage their withdrawal early and effectively.
Equally as important are the related psychosocial morbidities. Mental health disorders including depression and psychosis, concomitant alcohol abuse, and criminality are common in this demographic group. Patients may lack a stable place to live. Treatment may be complicated by social and political barriers to treatment and by a lack of resources for public health approaches to treatment.
4 How would you manage opiate dependency in the acute medical setting?
Short answer
Determine the degree of opiate usage by looking for needle track marks and undertaking urine toxicology. Withdrawal symptoms should then be controlled with methadone, either as advised by the community drug addiction team or empirically, starting at a low dose; look carefully for signs of drowsiness.
Long answer
Heroin is the most widely used opiate.17 Management ideally requires a multidisciplinary approach and may include a physician, infectious disease specialist, psychiatrist, general practitioner, social worker, key worker, support groups, and the patient’s family. However, these patients typically fail to engage with community support and thus put themselves and others at risk of morbidity.18 As a result, injecting drug users often present to acute medical services.
Begin the assessment by identifying the frequency, quantity, and tolerance of opiate use, and whether the patient uses new or used needles. It is particularly important to find out when the patient last had opiates. A history of any previous treatment for dependency and reasons for relapse will guide the approach to current rehabilitation if the patient wishes to engage. Examination should include an assessment of injection sites, including the antecubital fossa, as well as veins in the feet, hands, groin, and neck to look for signs of infection.19 Investigations may include testing for hepatitis B surface antigen and surface antibody, hepatitis C antibody, and HIV antibody (with consent), as well as a urine toxicology screen.
Opiate withdrawal symptoms can start as soon as four hours after the last dose of heroin. They reach a peak at 36-72 hours. Symptoms include yawning and sneezing, as well as more general withdrawal features such as sweating, tremors, and irritability.16 Patients withdrawing from opiates are likely to abscond, and they must be stabilised as rapidly as possible so that they remain compliant with other ongoing treatment.
Opiate withdrawal can be managed with opiate replacement therapy, which includes methadone and buprenorphine. Methadone is a long acting opiate that is initially administered daily by community drug and alcohol teams and community pharmacists under supervised consumption to prevent illegal selling. The aim is to get the patient on to a stable dose of replacement opiate, without using heroin on top.
If the patient claims to be on methadone, confirm the dose with the local community drug and alcohol team or pharmacy and whether that day’s dose has been collected. It is important to liaise closely with these teams because they can provide advice to prevent complications on the ward, such as dose correction for hepatic and renal impairment. In addition, early discharge planning helps to ensure that patients can access their methadone in the community on discharge.
If the patient is not on methadone, confirm that the patient is taking opiate drugs through urine toxicology, and then contact the community drug and alcohol teams for advice and to arrange for care after discharge should the patient want help. If this is not immediately possible (such as at the weekend), BNF guidelines state that methadone can be started at an initial dose of 10-40 mg daily and increased by 10 mg daily, with a maximum weekly increase of 30 mg. For patients with normal renal and hepatic function, we suggest starting methadone (1 mg/ml oral solution) at 10 mg twice daily, with an additional 10 mg prescribed as needed if the patient has ongoing withdrawal symptoms. Do not exceed 40 mg of methadone in the first 24 hours. Monitor for signs of opiate toxicity and document clearly on the prescription that methadone should not be given if the patient appears drowsy. Ensure that naloxone is prescribed and available as needed in the case of overdosing. Remember that naloxone is much shorter acting than methadone, so close monitoring is essential in overdose, and repeated doses of naloxone may be needed. Methadone can prolong the QT interval at high doses (>100 mg), and this should be monitored by electrocardiography.
Before discharge from hospital, discuss with the patient whether he or she wants to engage in opiate replacement therapy. If this is not the case, still consider referral to the community drug and alcohol team, which might be able to offer needle exchange programmes; education on safer injection techniques; free condoms; testing for HIV, hepatitis B, and hepatitis C; and hepatitis B immunisation to control the spread of bloodborne viruses.20
Patient outcome
S aureus (sensitive to flucloxacillin) was grown from two consecutive blood samples taken from our patient. Echocardiography showed tricuspid valve vegetation (fig 2). Our patient thus had two major Dukes’s criteria for the diagnosis of infective endocarditis. Because his plain chest radiograph (fig 1) showed bilateral lung consolidation, he was diagnosed with septic lung embolisation secondary to right sided endocarditis. He also had four minor Duke’s criteria—injecting drug use as a predisposing factor, fever (>38°C), microscopic haematuria as evidence of immune complex mediated vasculitis, and septic emboli.
Antibiotics for presumed community acquired pneumonia were immediately stopped and he was started on intravenous flucloxacillin at a dose of 2 g four times a day (as recommended in the latest guidance).9 He made a rapid clinical and biochemical recovery. However, after seven days, his fevers started to spike again. Repeat blood cultures were negative. The multidisciplinary team decided not to intervene surgically because the source of ongoing sepsis was thought to be the chest (not the infected tricuspid valve). An empyema was confirmed and drained. He completed six weeks of intravenous antibiotics as an inpatient and made an excellent clinical, biochemical, and radiological recovery. Repeat echocardiography showed severe tricuspid regurgitation, and elective tricuspid valve surgery is being considered. On discharge a detailed verbal and written case summary was sent to his community drug rehabilitation team to ensure continuity of his methadone prescription.
Notes
Cite this as: BMJ 2012;344:e1568
Footnotes
Competing interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent obtained.