Heaf Test Research Articles

Case-based discussion from the Royal Devon and Exeter NHS Foundation Trust: a painful paradox

Tumour necrosis factor (TNF)-α inhibitors, despite being an effective treatment for granulomatous diseases such as sarcoidosis and Crohn's, are recognised to trigger a paradoxical granulomatous response.1 ,2 Reported cases have...

Atypical Psoriasis Following Rituximab for Rheumatoid Arthritis: Figure 1.

To the Editor: Rituximab (RTX) is a chimeric B cell-depleting monoclonal antibody used in the treatment of non-Hodgkin’s lymphoma and rheumatoid arthritis (RA), and with an emerging role in connective tissue disease therapy. Its use has rarely been associated with skin reactions, in particular psoriasiform skin lesions. We report a case of atypical psoriasis reactivation in a patient with RA following RTX, and we review the literature. A 49-year-old woman presented in 1999 with a seronegative polyarthritis affecting the hands, elbows, feet, hips, and knees. At the time she gave no history of psoriasis. Over the next 10 years she received several disease-modifying antirheumatic drugs (DMARD) sequentially and in combination including sulfasalazine, hydroxychloroquine, methotrexate, azathioprine, gold, and leflunomide. Disease activity persisted, although radiographs remained nonerosive. Her 28-joint Disease Activity Score (DAS28) in September 2010 was 6.45 despite triple DMARD therapy, and she was assessed for a biologic. RTX was chosen in preference to anti-tumor necrosis factor (TNF) treatment because of recurrent shingles and a previous positive Heaf test (chest radiograph normal, quantiferon test negative). In November 2010 … Address correspondence to Dr. S.A. Hardcastle, Department of Rheumatology, Osprey Unit, The Great Western Hospital, Marlborough Road, Swindon SN3 6BB, UK. E-mail: Sarah.Hardcastle{at}bristol.ac.uk

Tuberculosis Screening Before Biologics — T-SPOT for All?

To the Editor: There remains considerable uncertainty and widespread variation in practice throughout rheumatology departments in the UK of screening methods for latent tuberculosis (LTB) prior to anti-tumor necrosis factor-α (anti-TNF-α) therapy. In recent articles, Pradeep, et al 1 used clinical history, chest radiograph, and Heaf testing, whereas Chikura and colleagues2 routinely used T-SPOT. On an international level, there is also marked variation in practice. In the USA, the tuberculin skin test (TST) is routinely performed in all patients. In Switzerland, all patients have an interferon-γ-release assay (IGRA), of which the T-SPOT is one example. The British Thoracic Society (BTS) guidelines3 suggest use of risk stratification if a detailed history, examination, … Address correspondence to Dr. S. Bawa, Rheumatology, Floor 7, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, G12 0YN, United Kingdom. E-mail: sandeep.bawa{at}ggc.scot.nhs.uk

Comparison of Interferon-Gamma Release Assay Versus Tuberculin Skin Test for Tuberculosis Screening in Inflammatory Bowel Disease

Comparison of Interferon-Gamma Release Assay Versus Tuberculin Skin Test for Tuberculosis Screening in Inflammatory Bowel Disease

Screening for Mycobacterium tuberculosis prior to anti-TNF therapy--an audit of impact of the British Thoracic Society guidelines on rheumatology practice in an area of low Mycobacterium tuberculosis prevalence

SIR, Anti-TNF drugs have revolutionized rheumatology practice. However, a major concern is the propensity for patients taking these drugs to develop reactivation of latent Mycobacterium tuberculosis (MTB) infection. The British Thoracic Society (BTS) has provided guidelines [1] on risk assessment for TB prior to commencing anti-TNF treatment, but how relevant is it in areas of low MTB incidence? We examined the pre-treatment screening methods adopted at two UK hospitals situated in the East Anglia region, an area of low MTB prevalence, from August 2000 to August 2005 and applied the BTS guidelines retrospectively to patients otherwise screened in order to evaluate whether it would have had an impact on our clinical practice. Patients with RA prescribed an anti-TNF drug at the Norfolk and Norwich and Ipswich Hospitals NHS Trust were identified from a pre-existing database and case notes reviewed with regards to pre-treatment screening methods employed. This included a detailed clinical history and physical examination, tuberculin skin testing (Heaf test was done at Ipswich only) and a chest radiograph. We also examined in detail the records of patients diagnosed as having latent MTB at the time of screening to see if there were any subsequent cases of active MTB. Three hundred and thirty-nine patients were screened and 326 were started on anti-TNF therapy (121 etanercept, 46 adalimumab and 159 infliximab), 329 were Caucasian, 1 Asian British, 1 Chinese and 8 did not have their ethnicity recorded. Three hundred and nine patients (91%) were taking additional immunosuppressive medication. Eighty-one (24%) had tuberculin testing done (Ipswich ¼ 78, Norwich ¼ 3), 7 out of 81 tests (8.64%) were found to be Heaf Grade 3–4, 41 of 81 tests (51%) were negative. Six patients (1.7%) had a previous history of MTB or treatment for it, 238 of 339 (92%) had a chest radiograph done prior to treatment and 4 (1.2%) had an abnormal chest radiograph consistent with old MTB. Fifteen patients out of 339 (4.4%) were referred to a local TB specialist of which 10 (66%) were diagnosed as having latent TB. Six of 10 (60%) patients suspected as having latent TB started isoniazid chemoprophylaxis. Four chose not to have anti-TNF treatment. None of the patients were found to have active MTB at the time of screening and after a median follow-up time of 4.35 yrs no patients have had reactivation of MTB.

Tubercular myocarditis presenting with ventricular tachycardia

A previously fit and healthy 30-year-old man reported experiencing palpitations accompanied by nausea, sweating and presyncope. These symptoms were found to be associated with episodes of nonsustained ventricular tachycardia. He was a nonsmoker, did not drink excessively, denied illicit drug use and had no family history of structural cardiac disease or sudden death. Electrocardiography, laboratory tests, electrophysiological studies, echocardiography, coronary angiography, chest radiography, cardiac MRI (with late gadolinium enhancement), chest CT, lymph-node biopsy, Ziehl Nielsen staining, blood and sputum cultures and heaf testing. Tubercular myocarditis. Antituberculous chemotherapy supported by antiarrhythmic and steroid pharmacotherapy and cardioverter-defibrillator implantation. Repeated imaging was performed to monitor disease progression.

Tuberculosis screening of asylum seekers: 1 years’ experience at the Dover Induction Centres

To describe the uptake and outcomes of a service for tuberculosis screening of asylum seekers. Descriptive study. A tuberculosis screening service was established at the Dover Induction Centres for all asylum seekers entering the UK through ports in Kent. This study describes the uptake and completion of tuberculosis screening, the results of tuberculin skin testing and follow-up, and the cost of the service during its first year. In 1 year, 8258 asylum seekers were screened: 94% of 8799 who were eligible. A total of 2.2% of those with completed screens were positive (on the basis of symptoms requiring further investigation or positive Heaf reaction). Eleven cases of active respiratory disease were diagnosed on the basis of symptoms, Heaf reaction plus chest X-ray, or both; three were confirmed microbiologically. One-quarter of Heaf tests were not read because of the rapid dispersal of asylum seekers. The follow-up of those requiring further investigations at their destinations was largely unknown. The service cost was 350,000 pounds. Induction centre tuberculosis screening services for asylum seekers can achieve a high uptake, but their cost-effectiveness is questionable, particularly where the yield of active disease is low. Tuberculin skin testing is not an ideal screening procedure in this setting because it may be uncompleted and the benefit of detecting latent infections is uncertain.

Rapid Development of Fatal TB Constrictive Pericarditis After Cardiac Surgery

We report the case of a 75-year-old male of Asian origin who developed TB constrictive pericarditis less than 6 weeks after CABG. He had no history of active TB, but did show a strong Heaf test reaction in 1987, following a period of weight loss. This was thought to be indicative of previous infection and was not actively treated. Cases of postcardiac surgery constrictive pericarditis have been reported in the literature, but to our knowledge, there is no report of development of TB constrictive pericarditis in such a short period following surgery.

Reduced tuberculin reactions with a single-use Heaf gun

The Heaf test was conventionally undertaken with a re-usable gun that required disinfection between subjects. Concern with cross-infection led to the development of a gun with a disposable head attached to a re-usable handle (Bignall Surgical Instruments) and, more recently, a single-use device (UniHeaf, Owen Mumford). Promotional literature states that the guns, respectively, contain pressure mechanisms that ensure proper skin penetration before needle release, or correct needle penetration even with the application of excessive pressure by an inexperienced operator. Both guns are recommended for Heaf testing as they avoid the need for disinfection, cleansing and maintenance. Pontypridd and Rhondda (PR) NHS Trust has an uninterrupted history of tuberculin testing on

Reactivation of tuberculosis after apparently adequate chemoprophylaxis

Screening of the close contacts of patients with pulmonary tuberculosis remains an important component in the control and prevention of the disease. It is carried out to identify active and latent infection, and those requiring BCG vaccination. Guidelines suggest giving chemoprophylaxis to asymptomatic contacts with a positive Heaf test (grades 2–4) and normal chest radiograph [Control and prevention of tuberculosis in the United Kingdom: code of practice 2000. Joint Tuberculosis Committee of the British Thoracic Society. Thorax 2000; 55:887–901]. We report a case involving a close contact where current guidelines were followed, but failed to prevent subsequent development of active disease from the same strain of M. tuberculosis.

Interferon-gamma and skin test responses of schoolchildren in southeast England to purified protein derivatives from Mycobacterium tuberculosis and other species of mycobacteria.

The immune responses of schoolchildren in southeast England to Mycobacterium tuberculosis and other species of mycobacteria were studied prior to vaccination with bacille Calmette-Guérin (BCG). Data are presented for tuberculin (Heaf) skin test and interferon-gamma (IFN-gamma) responses to M. tuberculosis purified protein derivative (PPD), and IFN-gamma responses to PPDs from eight other environmental mycobacteria, measured in 424 schoolchildren (13-15 years of age). Responses to M. tuberculosis PPD were detected in 27% of schoolchildren by in vitro IFN-gamma response and in 20% by the Heaf test. IFN-gamma responses were more prevalent to PPDs from species of mycobacteria other than M. tuberculosis, predominantly those of the MAIS complex and M. marinum (45-60% responders). Heaf test and IFN-gamma responses were associated (P<0.001) for M. tuberculosis, MAIS and M. marinum. These findings have implications for appropriate implementation of vaccination against tuberculosis.

Results of follow-up of human contacts of bovine tuberculosis in cattle during 1993-7 in North Staffordshire.

The purpose of the study was to describe the results of follow up of human contacts of bovine tuberculosis. The bovine tuberculosis cases occurred on farms in North Staffordshire between 1993 and 1997. A total of 162 people were identified as having close contact with cattle diagnosed as having bovine tuberculosis, or who had drunk unpasteurized milk from a herd with bovine tuberculosis. A retrospective review of chest clinic notes was performed. One hundred and thirty-eight people attended for follow up, and Heaf test results, necessity for chest X-ray and further clinical follow-up are described. No case of human Mycobacterium bovis infection was identified. It is suggested that follow-up of human contacts is limited to those with close contact with herds who have bovine tuberculosis and cattle with visible pulmonary lesions or evidence of udder infection. Children on the farms with affected cattle should also be offered BCG in advance of the routine school's programme.

Health Screening for Gurkha families in UK by chest X-ray, Heaf and blood testing: is it worthwhile?

This paper reports the chest X-rays, Heaf tests and haematology findings on a population of Gurkha wives and their children who arrived in the UK to accompany their husbands on...

Postmenopausal endometrial tuberculosis

Objective We describe a case of endometrial tuberculosis where confirmatory biopsy material was obtained by selective resection. The hysteroscopic appearance of tuberculous granulomas is discussed. Subject A 62-year-old woman presented with breakthrough bleeding whilst on hormone replacement therapy. Endometrial biopsy obtained at diagnostic hysteroscopy showed the presence of granulomas on histological examination. At a second hysteroscopy subepithelial nodules were seen and resected. Histological examination confirmed the presence of non-caseating epithelioid granulomas. The Heaf test was strongly positive. Conclusion Tuberculous granulomas can be seen hysteroscopically and selective resection will provide targeted biopsy material to aid diagnosis.

Administration of the BCG vaccination using the multipuncture method in schoolchildren: a comparison with the intradermal method

BACKGROUNDBCG vaccination using the multipuncture device (the Heaf gun) is recommended in the UK for infants and very small children only. The aim of this study was to investigate the...

Papulonecrotic tuberculide: a forgotten cutaneous manifestation of tuberculosis

A 30-year-old Chinese man presented with a 2-month history of enlarging neck masses and a widespread rash. He had first noticed the swellings 10 years ago when a diagnosis of tuberculosis was made. The lymphadenopathy improved after anti-tuberculous therapy but never completely regressed. Seven years later, a skin eruption developed over his limbs and trunk. He described recurring crops of asymptomatic reddish papules which discharged a yellowish fluid and subsequently healed with scarring and hyperpigmentation. There was no pruritus or tenderness and no pulmonary symptoms. Clinical examination revealed a non-tender, 10 cm, firm and ovoid mass with overlying erythema in the right anterior triangle of his neck (Figure 1) with several smaller lumps on the other side. There was a widespread eruption on his trunk and limbs, sparing the face, palms, sole and scalp (Figure 2). Recent lesions consisted of 1cm erythematous papules with a scaly collarette (Figure 3). Older lesions had left atrophic scarring and hyperpigmentation. A clinical diagnosis of papulonecrotic tuberculide was made. An X-ray of the chest was normal. Serum immunoglobulins (IgG, A and M) were moderately elevated. Erythrocyte sedimentation rate and C-reactive protein level were normal. Syphilis serology was negative. A Heaf test was strongly positive (Figure 4). Fine needle aspirations of the neck mass were negative for microscopic identification of acid-fast bacilli and for malignancy. On the other hand, a lymph node biopsy on the left side revealed fragments of connective tissue showing granulomatous inflammation and non-caseating necrosis. Occasional acid-fast bacilli were seen with a Ziehl-Neelsen stain. Skin biopsies were taken of recent, established and old lesions. The histological features of the established lesion were diagnostic, showing a florid, acute on chronic, perivascular and periappendiceal inflammmatory infiltrate involving both the superficial and deep dermis. There was also evidence of lobular panniculitis with fibrinoid necrosis of medium-sized arterial vessels, venulitis and extensive endothelial cell swelling. Histological features of the other two skin specimens were non-specific. No organisms were identified with special stains. Anti-tuberculous therapy with rifampicin, isoniazid and pyrazinamide was started and 2 weeks after treatment, the patient reported a complete cessation in the development of new skin lesions. His skin remains in remission after 6 weeks of treatment.

When is referral of Heaf test positive schoolchildren worth while? Prospective study.

Recent guidelines for controlling and preventing tuberculosis recommend that no further action is required for children with a grade 2 reaction to Heaf testing in the school pre-BCG screening programme.1 Fifty seven per cent of district health authorities, however, still recommend referral for such children.2 Furthermore, no guidance is given regarding contact tracing of children who are confirmed to be tuberculin positive but who have no signs or symptoms of clinical disease. We prospectively studied the results of screening children referred to our childhood tuberculosis clinic after a positive school Heaf test from January 1991 to August 1994 and tracing the contacts of these children. Newcastle Health Authority currently recommends referral of children with a positive Heaf test result of grade 2 or above to our childhood tuberculosis clinic. Tuberculin sensitivity is confirmed with a Mantoux test: 0.1 ml of 1:1000 purified protein derivative, read after 72 hours. …

Tuberculin testing in two Liverpool social clubs: the effects of a tuberculosis outbreak on background positivity.

Tuberculin testing remains the standard method for assessing infection due to tuberculosis in the UK. However, there are no data on the incidence of tuberculin positivity among the general adult population in the UK and consequently interpretation of Heaf test results is often difficult. During the investigation of an outbreak of tuberculosis in a Liverpool social club 198 members were interviewed and Heaf tested and 171 members of a second social club in Liverpool were similarly screened as a control group. Comparisons between the results from the two populations provided both an estimate of baseline Heaf test positivity in indigenous white adults from a British inner city population, and a measure of the effect on this baseline of recent exposure to tuberculosis. In both club populations the proportion of positive Heaf tests increased with age. Independent of age, the tuberculosis exposed population had a higher proportion of positive Heaf grade results (40.9%) than those in the control group (26.9%). Multivariate analysis confirmed both the differences in Heaf results between clubs and between age groups but identified no other behavioural or medical factors which affected Heaf test results. Heaf test positivity increases with age at least up to 54 years, and recent exposure to tuberculosis increases the proportion of positive Heaf tests in each age group. Interpretation of positive Heaf tests when assessing the effects of a tuberculosis outbreak should take account of background levels of Heaf positivity.

Enhanced expression of type 1 procollagen and transforming growth factor-beta in tuberculin induced delayed type hypersensitivity.

Tissue fibrosis is a common and serious consequence of chronic inflammation. The mechanism linking these two processes is poorly understood. The present study has utilised a human in vivo model of a delayed type hypersensitivity (DTH) reaction, the tuberculin Heaf reaction, induced by intradermal tuberculin in BCG immunised subjects, to dissect the relation between these two processes. Punch skin biopsy specimens were obtained on day 5, day 13 and six to 16 weeks following the tuberculin Heaf test in 18 subjects with grade 3 or 4 responses. Skin biopsy specimens from six subjects served as controls. The specimens were examined using immunohistochemical staining for type 1 procollagen and transforming growth factor-beta (TGF-beta), as well as in situ hybridisation for type 1 procollagen messenger RNA (mRNA). Immunohistochemical analysis revealed increased deposition of TGF-beta in tissue matrix in the biopsy specimens obtained on day 5 following the tuberculin Heaf test. There was also extensive type 1 procollagen staining in the biopsy specimens obtained as early as day 5. Procollagen-1 staining was maximal on day 13, and was present in biopsy specimens from tuberculin Heaf test sites up to eight weeks after the tuberculin inoculation. The type 1 procollagen was localised within cells surrounding areas of inflammatory infiltrate and in perivascular tissues. The presence of new collagen formation was confirmed by in situ hybridisation using oligonucleotide probes for type 1 procollagen mRNA in cells in sections from biopsy specimens obtained on day 13. These data from a human in vivo model of a DTH response indicate that the immune response is intimately associated with an increase in the production of growth factors and the initiation of a fibrotic response.

Use of the 1 tuberculin unit (TU) Mantoux test in the assessment of tuberculous infection in children following neonatal BCG vaccination.

BCG vaccination alters the response to tuberculin testing and influences the potential validity of the Heaf test in the diagnosis of tuberculosis. This study used a purified protein derivative 1 tuberculin unit (TU) Mantoux test with a cut off of 5 mm induration as an indicator of tuberculous infection in high risk children to determine whether this would distinguish infection from previous neonatal BCG vaccination. Children at high risk of tuberculosis on chest radiography, Heaf test, or contact history who had been screened in the contact tracing clinic and referred for further assessment were included in the study. After clinical examination, chest radiography, and Mantoux testing they were assigned to three groups (tuberculous disease, chemoprophylaxis, or no treatment) and followed up for 6-24 months in the outpatient clinic and subsequently by postal questionnaire. Comparison of the Heaf and Mantoux tests showed a difference in the results with 82% of cases positive by the Heaf test and 59% positive by the Mantoux test. Using the Mantoux test result in combination with clinical and radiographic findings 194 children were allocated to the three groups as follows: primary tuberculosis (5), chemoprophylaxis (101), no treatment (88). During follow up for a mean (range) time of 46 (11-102) months four additional cases received treatment for primary tuberculosis, two in the chemoprophylaxis group and two in the untreated group. The use of the 1 TU Mantoux test after neonatal BCG vaccination reduced the number of children receiving treatment from 129 to 93-that is, by 36%. Although the numbers are small, there was no increase in the later development of tuberculosis.