Is micropapular sarcoidosis tuberculosis? - Europe PMC

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Is micropapular sarcoidosis tuberculosis? Hilary A Ridgway MB MRCP Skin Department, St George's Hospital, London SW] 7 OQT

Terence J Ryan MD FRCP Department of Dermatology, Slade Hospital, Oxford OX3 7JH

Summary: Three cases of micropapular sarcoidosis are reported. Two of the cases have a history of tuberculosis and all three cases have atypical patterns of Kveim and Mantoux reactivity. The similarities between this form of sarcoidosis and lichen scrofulosorum or lichenoid tuberculid are observed and the evidence is presented for a tuberculoid aetiology in certain forms of sarcoidosis. Introduction The aetiology of sarcoidosis is unknown. However, for many years it has been suspected that mycobacteria may be implicated in at least some cases (Siltzbach 1969). There is considerable evidence for overlap between sarcoidosis and tuberculosis (Scadding 1964). The diseases have been observed simultaneously and sequentially in the same patient (Scadding 1950), in identical twins (Mikhail et al. 1970) and in the same family. Epidemiological studies have shown that in certain countries a surge in the incidence of sarcoidosis follows in the wake of an epidemic of tuberculosis (Morrison 1974). Scadding (1971) has demonstrated that the proportion of sarcoidosis patients with either active tuberculosis or positive tuberculin sensitivity has remained constant despite a relative decrease in the incidence of tuberculosis over the past 20 years. There is also experimental evidence for an interrelationship between sarcoidosis and tuberculosis from the demonstration of a transmissible agent in sarcoidosis (Mitchell & Rees 1969), the presence of precipitating antibodies against mycobacterial antigens in sarcoidosis patients (Chapman et al. 1967), and the isolation of Mycobacterium tuberculosis from sarcoidosis patients (Richter et al. 1971) and from sarcoid-inoculated mice (Mitchell & Rees 1980). Three patients are now reported in whom a diagnosis of micropapular sarcoidosis was made but who demonstrate a considerable degree of overlap with tuberculosis. The similarity between micropapular sarcoidosis and both lichen scrofulosorum and lichenoid tuberculid was also observed. Case reports Case 1: A 52-year-old Caucasian woman developed itchy red papules on the arm and leg in December 1978. Over the following months she developed successive crops of lesions all over her limbs and trunk. She had a brief episode of painful red eyes in August 1979 but ophthalmological examination in September 1979, including the use of the slit-lamp, was normal. She was otherwise asymptomatic although she had been on griseofulvin for 10 years for tinea unguium. Her past history included two episodes of active tuberculosis in 1952 and 1976. She was treated on both occasions with triple therapy and on the second occasion rifampicin and isoniazid were continued for one year. Examination revealed an extensive eruption consisting of sheets of coalescent pink and yellowish-brown, slightly scaly papules on the limbs and trunk, but sparing the face, palms and soles (Figures 1 & 2). No other abnormality was found on general examination. 'Paper based on case presentations 0 141-0768/81/020140-05/$O 1.00/0

to Section of Dermatology, 17 January 1980. Accepted 25 November 1980

(7o 1981 The Royal Society of Medicine

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Figure 1. Case 1: micropapular sarcoidosis on the back

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Figure 2. Case 1: grouped micropapular lesions on the leg

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Figure 3. Case 1: skin histology demonstrates a sarcoid granuloma in the upper dermis. ( x 100)

Skin biopsy showed typical sarcoidal granulomata (Figure 3). No acid-fast bacilli were seen and cultures were negative. The Kveim test was initially negative but it was positive when repeated on two subsequent occasions with two different validated antigens. Her chest X-ray showed old tuberculous scarring only; the Mantoux, however, was strongly positive at 1 in 100 000 tuberculin units. Investigations yielding normal results included ESR, full blood count, serum electrolytes, liver function tests, plasma and urine calcium and repiratory function tests. Immunological investigations (including studies by Dr H Valdimarsson, St Mary's Hospital), failed to show any significant degree of T cell suppression or B cell overactivity.

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Figure 4. Case 2: detailed view of micropapular lesions on the abdomen

Case 2: (This case was previously reported as lichen scrofulosorum (Smith et al. 1976).) A 71year-old woman was treated in 1966 for cervical lymph node tuberculosis (confirmed on culture) with a 12-month course of isoniazid and calcium benzamidosalicylate. She first developed a micropapular rash involving the trunk and legs in 1973, six months after the onset of anterior uveitis. Histology at that stage was consistent with sarcoidosis. Over the following months the rash became more florid (Figure 4). Investigations in 1974 included a further skin biopsy which confirmed the presence of non-caseating granulomata, a negative Kveim test and a positive Mantoux test at 1 in 10 000 tuberculin units. A diagnosis of lichen scrofulosorum was made and the rash resolved three months after starting a 1 year course of rifampicin and isoniazid. Since 1974, her uveitis has persisted and in July 1979 the rash recurred on her trunk and legs. She has otherwise been well. On examination in 1979, she had a micropapular rash on the trunk and legs consisting of scattered solitary papular lesions 2-4 mm in diameter, as well as confluent discoid or annular groups of sightly scaly lesions in the more classical pattern of lichen scrofulosorum. No other abnormalities were found. Investigations included normal full blood count, ESR and serum biochemistry. The chest X-ray showed no evidence of active tuberculosis. Her Mantoux was at this stage initially negative but on subsequent testing was again weakly positive. Kveim test was negative. Repeat skin biopsy showed non-caseating epithelioid granulomata. Case 3: A 70-year-old woman developed an itchy rash on her arms and legs in 1976, which persisted over the following three years. She was otherwise well. Examination revealed a rash on the legs which was initially red and nonspecific but later developed into a papular eruption consisting of small brownish and sometimes translucent lesions. There were also lesions resembling 'acne agminata' around the eyes. Investigations were all normal or negative and included full blood count, ESR, serum biochemistry, urine calcium excretion, chest X-ray, bone marrow, Wassermann reaction, antinuclear factor, latex, liver biopsy, Kveim test and 1 in 100 Mantoux. A skin biopsy showed non-caseating granulomata. (At the same meeting of the Section of Dermatology a case of periorbital and axillary acne agminata was shown to demonstrate the similarity of the lesions. It is of interest that he also had phlyctenular conjunctivitis (see below). All investigations including Mantoux 1 in 100 and Kveim tests were negative.)

Discussion

Micropapular sarcoidosis is a relatively uncommon form of cutaneous sarcoidosis which has a distinct female preponderance and which, in general, has a good prognosis (James 1959,

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Scadding 1967). Although there may be evidence of systemic involvement, progressive lung disease is less common than in other forms of skin sarcoidosis. Ocular involvement, however, appears to be a relatively frequent association (James 1959, Gange et al. 1978). The three cases reported here appear to comply well with previous descriptions of this form of the disease. They are all female and presented with multiple small pink or brown papules, often clustered and situated mainly on the trunk and limbs. Histology of all the cases showed non-caseating, epithelioid granulomata situated in the upper dermis. Cases I and 3 noted pruritus and this has been described previouly (Fong et al. 1975). None of the cases had evidence of lung sarcoidosis but cases 1 and 2 had possible ocular involvement. The special interest in these cases, however, is with regard to Kveim and tuberculin reactivity. Both cases 1 and 2 have a bacteriologically proven past history of active tuberculosis which was assumed to have been treated effectively with drug therapy. Case 1 retained strong sensitivity to tuberculin but showed no other evidence of active tuberculosis. Although an initial Kveim test was negative, two subsequent tests were both positive. Case 2 demonstrated a variable degree of reactivity to tuberculin, but the Kveim test was negative. Case 3 was unreactive to both tuberculin and Kveim. It is evident, therefore, that none of the three cases demonstrate the combination of Kveim-positivity and tuberculin hyporeactivity which is characteristic of sarcoidosis. It should, however, be noted that in sarcoidosis the Kveim test may be positive in only approximately 72% of patients (Mikhail & Mitchell 1970) and tuberculin reactivity is seen in up to half (Scadding 1967). Also, in tuberculosis there is a wide range of sensitivity to tuberculin skin tests and some patients with active disease have persistently negative reactions (Scadding 1956). We have observed a close similarity between our own and previously reported cases of micropapular sarcoidosis (James 1959, Gange et al. 1978) and some reported cases and textbook descriptions of lichen scrofulosorum (Hebra 1868, Smith et al. 1976, Sutton 1949, Ormsby & Montgomery 1953) and of lichenoid tuberculid (Ockuly & Montgomery 1950). This applies to the clinical history and appearances, to the histology and also to the inconsistent Kveim and tuberculin reactions. With particular regard to the clinical manifestations of the disease, it is of note that lung involvement is usually absent in lichen scrofulosorum (Hebra 1868) and lichenoid tuberculid (Ockuly & Montgomery 1950) but that ocular involvement has been present in a number of cases (Rauschkolb 1934, Smith et al. 1976). Volk (1931) suggested that women were more commonly affected in the old age group. Lichen scrofulosorum was'first described by Hebra in 1868 and both he and other writers since (MacLeod 1933) have recognized that it occurs typically in children with active lymph node tuberculosis associated with severe malaise and cachexia. It is well recognized that in the Western world, the pattern of presentation of tuberculosis in general has been changing with the increasing degree of natural and induced resistance; tuberculosis now more commonly presents at an older age and the relative incidence of extrapulmonary and nonpulmonary disease is increasing (Grange 1979). Could our observed increase in the number of cases of lichen scrofulosorum simply be a cutaneous reflection of the changing picture of tuberculosis? In conclusion, we would like to suggest that micropapular sarcoidosis may be identical to lichen scrofulosorum and lichenoid tuberculid. This could provide supportive evidence to the hypothesis for a mycobacterial aetiology for some cases of sarcoidosis. Older textbooks (Sutton 1949) may have been correct to use the caption 'Hypoergic Tuberculids (Sarcoid)'.

Acknowledgments: We are grateful to Dr S C Gold for his permission to report case 1. Cases 2 and 3 were presented at this meeting by Dr Jonathan Leonard. References Chapman J S, Baum J, Clark J & Speight M (1967) American Review of Respiratory Diseases 95, 612-617 Fong Y W & Sharma M D (1975) Archives of Dermatology 111, 362-364 Gange R W, Smith N P & Fox E D (1978) Clinical and Experimental Dermatology 3, 299-306 Grange J M (1979) British Journal of Hospital Medicine 6, 540-548

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Hebra F (1868) In: Diseases of the Skin. Transl. and Ed. C H Fagge and P H Pye-Smith. New Sydenham Society, London; vol 2, p 52 James D G (1959) Quarterly Journal of Medicine 28, 109-124 MacLeod J M H (1933) Diseases of the Skin. 2nd edn. H K Lewis, London: pp 487-489 Mikhail J R & Mitchell D N (1970) Postgraduate Medical Journal 46, 484-485 Mikhail J R, Mitchell D N & Drury R A B (1970) American Review of Respiratory Diseases 102, 636-640 Mitchell D N & Rees R J W (1969) Lancet ii, 81-84 Mitchell D N & Rees, R J W (1980) In: Proceedings of the Eighth International Conference on Sarcoidosis and other Granulomatous Diseases. Ed. W Jones Williams and B H Davies. Alpha Omega Publishing, Cardiff; pp 121-132 Morrison J G L (1974) British Journal of Dermatology 90, 649 Ockuly 0 E & Montgomery H (1950) Journal of Investigative Dermatology 14, 415-426 Onnsby 0 S & Montgomery H (1953) Diseases of the Skin. 8th edn. Henry Kimpton, London; pp 954-955 Rauschkolb J (1934) Archives of Dermatology and Syphilis 29, 398 Richter J, Bartak F & Havlova R (1971) In: Fifth International Conference on Sarcoidosis. Ed. L Levinsky and F Macholda. University Karlova, Prague; pp 375-378 Scadding J G (1950) British Medical Journal i, 745-753 Scadding J G (1956) Tubercle 37, 371-380 Scadding J G (1964) Acta Medica Scandinavica 176, Suppl 425; pp 266-267 Scadding J G (1967) Sarcoidosis. Eyre and Spottiswoode, London Scadding J G (1971) In: Fifth International Conference on Sarcoidosis. Ed. L Levinsky and F Macholda. University Karlova, p 89 Siltzbach L E (1969) The Practitioner 202, 613-618 Smith N P, Ryan T J, Sanderson K V & Sarkany 1 (1976) British Journal of Dematology 94, 319-325 Sutton R L (1949) Handbook of Diseases of the Skin. Mosby, St Louis; pp 215-217 Volk R (1931) Handbuch der Haut-und Geschlechtskrankheiten. Ed. J Jadassohn. Springer, Berlin; vol 10, p. 331