Trevor Silver Memorial Essay Prize 2014 Second Prize

Claire Wand fund essay 2014

A swollen knee  - C Ruth Butlin 

Case history

The patient was a 46 year old male, a bricklayer of Asian origin, who complained of a swollen painful knee for the past 12 months. For 8 months he had been unable to work, and 6 months prior to my meeting him he had consulted a private practitioner in his home country. This doctor had made a drainage incision in his leg below the knee, and there was a continuous slow seepage of fluid from the site. His past medical history included fully treated leprosy, no particular trauma, and nothing else of note.

On examination the man was afebrile, he appeared well-nourished but not overweight, he walked with a limp. His right knee was swollen with an effusion detected by manual palpation, but not hot to touch and not very tender. There was wasting of quadriceps muscle on the right side. Below the knee on the medial side of his affected leg there was a sinus draining clear honey-coloured viscous fluid. There was no peripheral nerve function impairment nor secondary deformity due to leprosy. General physical examination revealed no abnormalities in other systems, in particular chest examination was normal.

With the long history and the signs of chronic inflammation, although the patient was not complaining of fever nor weight loss, I suspected tuberculous infection of the knee joint or adjacent bone, so I arranged an X-ray of the knee (which was unhelpfully normal-looking), and a chest X-ray (which was also normal), and sputum microscopy which was AFB-negative (ie no Acid Fast Bacilli seen) as well as some basic blood tests (which showed mild anaemia and a white cell count within the normal range). Microscopy of the draining fluid was also negative for AFBs and “routine” culture showed “no growth”. His temperature was monitored but he had no fever. Meanwhile the patient was kept mainly at rest with the leg elevated and adequate oral  analgesia; a daily dressing was put on his sinus and he was allowed to move about with crutches for essential purposes only.

An orthopaedic surgeon saw the case within 1 week. He decided to explore the sinus as well as aspirate synovial fluid from the knee joint for culture and direct microscopy. A biopsy was taken from the proximal end of the sinus, and within 2 weeks we received the histology report: granulomatous inflammation consistent with tuberculosis (v.i.). Unfortunately our local laboratory does not undertake Tb culture so no sensitivity pattern could be obtained from the synovial fluid for the M. tuberculosis.

Before discharge from hospital the patient was put in touch with local Tuberculosis services for treatment according to national guidelines. Six months later I met him again, looking very fit and happy. He had almost completed the anti-tuberculosis treatment (with no adverse effects) and was walking comfortably without crutches. The sinus was neatly healed up and the knee no longer swollen. Having been advised to take things slowly he had not yet returned to his manual labour job but did feel ready to resume work.

Swollen knees in general practice

Knee problems are an exceedingly common reason for attending a general practice. It can be difficult to distinguish those which represent a serious diagnosis that needs urgent intervention from the ones where symptomatic treatment and observation are more appropriate. History must be elicited in detail before embarking on physical examination: past trauma, other illnesses, previous treatment (home remedies, physiotherapy etc as well as prescriptions or surgery) and its effects should be recorded. Physical examination will include inspection and palpation of the knee before tests of movement, stability and so on. The pattern of abnormalities in any other  swollen or painful joints could also give a clue to the differential diagnosis.

In this case the lack of trauma, the duration, the presence of an effusion and the lack of warmth/acute tenderness were all suggestive of a chronic infection, but compatible with non-infectious arthritis. The discharging sinus was a major clue to the type of problem involved.

 

 Tuberculosis in human body

The most important source of new infections numerically is “open cases” who inadvertently contaminate the environment with sputum or droplets from exhaled air, but new diagnoses of tuberculosis in UK are commonly due to reactivation of endogenous infection, which cannot be prevented by environmental hygiene.  Extra pulmonary tuberculosis is usually the result of haematogenous spread from a primary focus (which could be pulmonary or in the gut) or a result of delayed reactivation of latent disease associated with immunosuppression. It may affect lymph nodes, skin, pleura, percardium, peritoneum, genital organs, eye, meninges, or bones and joints,. Systemic signs and symptoms will be as for pulmonary Tb: fever, weight loss, malaise, often chronic anaemia. Local signs and symptoms obviously depend on the specific site.

Skeletal tuberculosis typically affects weight –bearing joints, and is characterised by persistent low grade inflammation with pain but little early change detectable on simple X-ray examination. Radiological signs of more advanced tuberculous infection would be bone erosions, narrowing of the joint space, and ultimately joint destruction (5b).Computerised tomography or magnetic resonance imaging may show otherwise undetectable radiological changes . Bone or synovial biopsy samples  may show the characteristic histological picture, or give a positive result on culture for Mycobacterium tuberculosis. Alternatively synovial fluid obtained from arthrodesis may give a positive culture (a less invasive test).

Tuberculosis in general practice

Pulmonary tuberculosis is a major public health problem in many parts of the world but in UK it is a diagnosis a typical general practitioner would rarely make. There may be undiagnosed cases passing through our surgeries if awareness is low, and chronic cough is attributed to Chronic Obstructive Pulmonary Disease or haemoptysis first suggests the possibility of lung cancer. Extra pulmonary tuberculosis is uncommon in UK. However the risk is higher in immigrant populations from countries where overall Tb prevalence is higher than in UK.

World wide (in 2012) approximately 8.6 million people developed Tb (and 1.3 million died from the disease), one in five registered cases had extra-pulmonary disease (8). Half those with extra-pulmonary disease may also have pulmonary tuberculosis(5b).

 There were 8,751 cases reported in UK in 2012 (6), which represents an incidence rate of 13.9/100,000 overall but 6.6/100,000 in people over 75 years old, and 4.4/100,000 in UK-born people. More than 70% of the reported cases were in people born abroad in high incidence countries and half of these presented within 5 years of coming to UK. Over half (53%) had pulmonary disease but 1/5 of these also had disease in an extra-pulmonary site. Many patients were diagnosed late: compared with those diagnosed <90 days after onset of symptoms, those with late diagnosis were more likely to be older and to have extra-pulmonary disease (6)

Apart from ethnic or social groups at higher risk because of their previous place of residence, the people who should be considered at special risk of tuberculosis are the elderly, diabetics, those who abuse alcohol (or intravenous substances), those with chronic renal failure, coal miners or anyone suffering silicosis, and those  who are immunosuppressed (not only HIV positive cases but also those on immune-modulating  drugs for auto-immune diseases, or as part of cancer therapy, or following transplants. A high index of suspicion for tuberculosis is probably more common amongst doctors who have trained or worked abroad in resource-poor countries than amongst doctors who have spent their whole professional lives in UK!

For suspected pulmonary tuberculosis the first important investigation is sputum for microscopy for acid fast bacilli. Modern techniques have greatly improved sensitivity of this diagnostic test, but in all cases culture for the tubercle bacillus should also be done even if microscopy is negative on 3 samples. A negative sputum does not rule out Tuberculosis infection but it does mean that the patient  is not infectious . Sputum negative suspects with pulmonary symptoms should have a chest X-ray which is repeated after a trial of antibiotic therapy . If there is still doubt a referral to a chest physician would be advisable.

For extra-pulmonary tuberculosis, it is usually necessary to have biopsy material for histology to confirm the diagnosis, although sometimes a culture of pus or body fluids will give the definitive diagnosis. UK guidelines recommend that “the appropriate treatment regimen should be started without waiting for culture results if the histology and clinical picture are consistent with a diagnosis of TB” and that “all patients with non-respiratory TB should have a chest X-ray to exclude or confirm co-existing pulmonary tuberculosis.”(4). Differential diagnosis may include other granulomatous conditions such as sarcoidosis (1), Crohn`s disease or infection with atypical mycobacteria.

 

In resource-poor countries diagnosis of extra pulmonary Tb is particularly difficult (7), but of vital importance especially where HIV is  endemic. Extra pulmonary disease is more closely associated with HIV positivity than is pulmonary disease, and it is classified as a criterion for stage 4 in “Clinical staging of HIV”. Simplified standardised guidelines for diagnosis and management of such cases in resource-constrained settings have been produced (7) but in UK there should be no problem to access specialised diagnostic services for individualised management (4).

 

In this country, Tuberculosis has long been a notifiable disease: notification to the local authority will trigger a response to allocate a named key worker and to initiate contact screening (whatever the site of infection in the index case). Overall about 1% contacts will be found to have active tuberculosis, whilst 20-30% are likely to have latent Tb. The risk of latent Tb later becoming active is reduced by 60% with chemoprophylaxis.

In this case the patient`s household contained no symptomatic people and no-one of an age eligible for chemo-prophylaxis. Children up to age 12 in contact with an open case of tuberculosis should be offered prophylaxis with isoniazid (10mg/kg/day  up to a maximum of 300mg/day) for 6 months. Children under 6 years old from countries like his place of origin with tuberculosis prevalence over 40/10000, who are contacts of known Tb cases, if not previously vaccinated, should be offered BCG  but only after confirming their skin test for tuberculin hypersensitivity is negative. A positive test could indicate current infection. Interferon gamma release assay (IGRA) is now available for detecting latent infection which might need treatment, in contacts; this is a more sensitive test than the traditional Mantoux reaction (4).

According to a decision of the Joint committee on vaccination and immunisation, BCG policy  in UK was changed in 2005 from a school-based to a risk-based strategy:  it is now advised for  neonate with  a positive Family History <5yrs ago; all neonates and infants born in areas with incidence >40/100000; neonates, infants, children <16yrs old of parents born in a high incidence country; new immigrants <16yrs old who lived >3months in a high incidence country; contacts of those with pulmonary Tb; new immigrants 16-18yrs old from countries with incidence >50/100000 (also if <16yrs old and  going to live>3months in a high incidence country) (6). However most highly endemic countries have a policy for universal BCG vaccination soon after birth.

Anti-Tuberculosis Treatment

Although there is increasing anxiety world –wide about drug resistance in tuberculosis, fortunately most people with a new diagnosis still respond to standard drug combinations. In 2012, only 7.1 % newly registered case in UK had resistance to one or more of first line anti-tuberculosis  drugs, but the rate was higher in non-UK-born patients and in those (6% of all cases ) with a previous  diagnosis of Tb (6). However strict compliance in all cases is essential not only for the individual`s own recovery from infection but to ensure he does not develop drug resistance which might be spread to others. “Directly Observed Short Course Therapy” is the ideal, but is often modified to suit particular situations, eg another responsible person- instead of a health worker- observes the daily intake of drugs. Each newly diagnosed tuberculosis patient will undergo a risk assessment for likely adherence to the recommended regimen (4), and be offered information about his disease in a culturally appropriate form, with an invitation to participate in decision making as far as is feasible & acceptable for him.

Should the Risk assessment indicate that the patient is at high risk for drug resistant Tuberculosis, “rapid diagnostic tests” will be arranged to identify the drug sensitivity pattern, without delaying start of treatment (4)

Standard chemotherapy for all forms of Tuberculosis in UK (for patients expected to be able to comply,  with body weight 40-49kg) consists of   combination tablets of rifampicin /insoniazid /pyrazinamide (480/200/1200 mg daily) plus ethambutol 15mg/kg daily for the first 4 months; thereafter for 2 months  combination tablets of rifampicin/isoniazid (450/300mg daily).

In his own country, being in “category 3”  ( sputum negative pulmonary, or extra-pulmonary), prior to 2009 this patient would have received only rifampicin/isoniazid/pyrazinamide (450/225/1200 mg per day) as fixed dose combination tablets daily for 2 months  then rifampicin/isoniazid (450/225 mg per day) for 4 months, and no ethambutol (5a). Recently the protocols have been simplified to use only two regimens, category 1 for all new cases and category 2 for retreatment (5b).

Possible adverse effects of the combination drug therapy  include hepatotoxicity, allergic reactions, visual impairment (ethambutol) and arthralgia (with pyrazinamide). All patients will have red colouration of urine due to rifampicin which can be frightening if they are not warned in advance. Many will experience mild nausea. Any patient starting treatment for tuberculosis should be educated in advance about the duration and possible risks of the course prescribed, importance of compliance and what benefit to expect . Recommended monitoring would include visual acuity and colour vision testing as well as liver & renal function tests.

Tuberculosis in Asian people

In parts of Asia, despite well-designed Tb control programmes and valiant efforts from health workers employed by government and non-government organisations, many patients take incomplete course of anti-tuberculosis therapy. In some cases this is a result of private practitioners treating people with unorthodox regimens, or failing to follow up cases adequately. Other reasons include difficulty in reaching clinics, irregular drug supply to clinics, and patient-factors such as not understanding the need to complete a full 6 months` course, without gaps. Incomplete courses of treatment predispose to development of drug resistance, so it is important for a general practitioner in UK  when diagnosing tuberculosis in an immigrant/foreign student/refugee/asylum seeker to sensitively enquire about any previous anti-tuberculosis therapy.

One needs to remember that in some countries tuberculosis is considered a stigmatising disease and thought by lay people to be hereditary. The fact that tuberculosis control and leprosy control programmes are often combined and share clinic premises is not always helpful to clients of either programme, if they wish to take medicine discretely without neighbours/social contacts discovering their diagnosis.

There is also in some areas a problem for people affected by leprosy to access proper treatment for other medical conditions, if they are unwelcome in a public hospital general out-patient department but there is no doctor (only a leprosy technician) at the leprosy clinic, or if all their signs and symptoms are casually misattributed to leprosy. In this case the patient had earlier been seen at a leprosy clinic (in his own country) where his discharging sinus was wrongly labelled as a trophic ulcer.

Conclusion This patient had suffered unnecessarily long on account of inappropriate early management and failure of the first doctor who saw him to suspect the diagnosis. However he finally had a good outcome. Although tuberculous infection of a joint is rare in UK practice, it is an easily treatable condition and a significant finding in the public health context as it may be a clue to identifying a focus of open Tb infections within the patient`s circle of contacts.

References

  1. Ashdown HF, Ho L-P, Haynes JE. Lumps, bumps and diagnostic stumps. BJGP, 2013, 63,

p. 663-664

  1. British National Formulary for children 2012-13
  2. British National Formulary,  65, March- Sept 2013
  3. National institute of clinical excellence, Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control, Issued: March 2011, NICE clinical guideline 117 guidance.nice.org.uk/cg117

5a. National Tuberculosis control programme/directorate general of health services, Government of Bangladesh. National guidelines and operational manual for tuberculosis control, 3rd edition, 2004

5b. National Tuberculosis control programme/directorate general of health services, Government of Bangladesh. National guidelines and operational manual for tuberculosis control, 4th edition, 2009

  1. Public Health England, Tuberculosis in the UK: Annual report on tuberculosis surveillance in the UK, 2013. London, August 2013.
  2. World Health Organisation 2007.  Improving the diagnosis and treatment of smear-negative pulmonary and extra-pulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource constrained settings.

 WHO /HTM /TB /2007.379 WHO /HIV/2007.01

  1. World Health Organisation 2013.   Global Tuberculosis Report. Available at www.who.int

 

 

 

I am a locum general practitioner based in Sussex, currently undertaking voluntary work with The Leprosy Mission in Bangladesh.

Previously I worked as sessional GP for the Old School Practice (Seaford) at their Alfriston surgery in East Sussex. Before that I served abroad as a missionary doctor in the Indian subcontinent.

Dr C Ruth Butlin, 42 Old Drive, Polegate, East Sussex, BN26 5ES

[email protected], [email protected]

 

The patient is a real person, the clinical history and findings are faithfully described, but the person`s identity has been carefully disguised. His written informed consent was not sought when he was seen as there was no intention to publish his case in a journal. It would not be possible now to obtain  such consent.

 

 

Biopsy report: "Epithelioid cell granulomas containing Langhan's type of giant cells. Moderate number of chronic inflammatory cells including polymorphs  is also present. No caseation necrosis or malignancy is seen.  Diagnosis: Granulomatous inflammation, suggestive of tuberculosis."