BY. J. Dis. Chest (1976) 70, 125
EOSINOPHILIC
GRANULOMA A. R.
King’s
OF THE LUNG
DAVIDSON
College Hospital,
London
Summary Pulmonary the remission
eosinophilic granuloma and relapse that may
diagnosed occur.
by lung
biopsy
is described;
the
case
demonstrates
Eosinophilic granuloma or histiocytosis X sometimes presents as a widespread infiltration of the lungs. In some cases this is accompanied by extra pulmonary changes, especially in bone. Pulmonary eosinophilic granuloma is rare. The first cases were described in 1951 (Farinacci et al. 1951). The clinical course is unpredictable. This report describes one case of a man who received no treatment and had a radiological remission lasting three years. Case Report A 27-year-old lorry driver had a tonsillectomy in October 1964 for recurrent tonsillitis; a small postoperative haemorrhage was easily controlled. A chest radiograph the following day showed ‘generalized miliary mottling’. At this time he was symptom-free. Readmission for investigation showed that he had a haemoglobin of 97 mg/lOO ml, white blood count 7200, ESR 20 mm, platelets 157 000 and prothrombin 100%. The urea and electrolytes were normal; serum calcium 9.6 mg/lOO ml. Liver function tests were normal. Total plasma proteins were 6.9 g/100 ml. Eight sputum examinations failed to reveal any acid-fast bacilli and sputum cultures were always negative. Bronchoscopy showed no abnormality. Bronchial biopsy showed normal bronchial mucosae. Scalene node biopsy was also normal and as no diagnosis had been reached at this stage a diagnostic lung biopsy was undertaken. At operation through a small left thoracotomy the lung surface was noted to be studded with small sago-grain-like nodules. The microscopic appearance of the lung showed granulomatous lesions which under high power showed an infiltration with many varieties of cells, including histiocytes, lymphocytes and plasma cells (Fig. l), all characteristic of eosinophilic granuloma of the lung. A skeletal survey at this time showed one lesion in the left parietal bone. No treatment was deemed necessary as the patient was symptom-free. He was reviewed regularly after discharge, remaining symptom-free. By April 1966 his chest radiograph had begun to clear and by March 1967 there was no abnormality on it and the left parietal lesion had also cleared. He remained well until March 1970, when he presented with pleuritic left chest pain, weight loss and shortness of breath on exertion. Physical examination was normal. A chest radiograph showed a recurrence of the diffuse miliary appearance, but there was now a lesion in the right third rib posteriorly and a recent cough fracture in his right fourth rib. He was thought to have widespread disease, and prednisone 20 mg/day was started. He made a good symptomatic recovery but with no change in his chest radiograph. Prednisone therapy was discontinued after six months : at this time he was symptom-free but the chest radiograph had not improved. Regular reviews as an out-patient showed no change clinically or radiologically. By March 1973 he had been followed for Sg years in all, and three years after radiological relapse, he was still
126
A. R. Davidson
Fig.
symptom-free the course insipidus.
2. Lung
biopsy
but the chest radiograph of his disease had he had
in eosinophilic
granuloma.
had not changed over the a spontaneous pneumothorax
H & E x 350.
last three years. or any symptoms
At
no time in of diabetes
DISCUSSION The term histiocytosis X was first used by Lichtenstein in 1953. He considered that the skeletal and soft tissue lesions represented various manifestations of the same disease, due to proliferating histiocytes (Lichtenstein 1953). The traditional terms are still in common use, they are eosinophilic granuloma for patient with bone lesions only, Hand-SchullerChristian syndrome for a chronic slowly advancing involvement resulting chiefly in symptoms from bones and Letterer-Siwe syndrome for children with a rapid visceral spread, often involving bone as well. Parkinson in 1949 predicted that eosinophilic granuloma would be found early in the lungs, but it was two years later that the first two cases of solitary eosinophilic granuloma of the lung, confirmed at biopsy, were described (Farinacci 1951). Since then it has been reported in increasing frequency and has become an important differential diagnosis of diffuse pulmonary infiltration, in one series accounting for 2.6% of all patients with miliary lung disease (Knudson et al. 1966). Primary pulmonary eosinophilic granuloma predominates in males, with a male to female ratio of 5 : 1. The usual age range is 15 : 20 years (Weber et al. 1969). The onset is insidious. The disease may be found on routine chest radiographs in symptom-free patients. Presenting symptoms are few and include cough, chest pain, shortness of breath and weight loss (Weber et al. 1969). Rarely patients may present later with severe dyspnoea and a chest radiograph of honeycomb lung (Grant & Ginsburg 1955). The diagnosis is made by open lung biopsy (Stanford et al. 1971) or drill biopsy.
Eosinophilic Granuloma of the Lung
127
There are two well recognized complications. Pneumothorax occurs in 20-30 o/o (Hoffman et al. 1962). In some cases the pneumothorax may be recurrent, needing surgical correction, and this recurrence may be explained by subcortical bleb formation (Knudson et al. 1966). Diabetes insipidus is reported in 21%. The pathology of this is unknown, but it may be due to some involvement of the hypothalamic-hypophyseal system (Hoffman et al. 1962). Most reported patients have been followed for a short period only, but there are reports of a few patients followed for up to nine years (Hoffman et al. 1962; Lewis 1963). It is known that the disease runs an unpredictable and usually benign course, occasionally with spontaneous remission (Nadeau et al. 1962). Our patient had no treatment when he first presented. He had a slow and complete radiological remission in both his chest and his skull. We have found no previous reports of eosinophilic granuloma of the lung relapsing after a remission. In this patient there was no obvious cause for the relapse. At this time he had chest pain, shortness of breath and weight loss. There is no agreed treatment of this condition. Radiotherapy gives excellent results when the lesion is limited to bone but seems contraindicated in pulmonary disease, as large doses will give rise to further pulmonary fibrosis and small doses are ineffectual (Nadeau et al. 1960; Hoffman et al. 1962). Corticosteroids are advocated early in the disease, but spontaneous remissions occur without therapy and there is no real evidence that they alter the natural course of the disease (Knudson et al. 1966). However, certain patients with symptoms may benefit from corticosteroid therapy (Stanford 1971) and certainly our patients rapidly became symptom-free with prednisone.
ADDENDUM
Since this report was prepared the patient has developed no new respiratory symptoms or signs. However, in October 1974 he presented with a short history of polyuria and polydipsia, which were found to be due to diabetes insipidus. This is now well controlled with lycine, vasopressin nasal spray and chlorpropamide.
ACKNOWLEDGEMENTS
This paper is published by kind permission of Dr J. H. Dadds, Consultant Saint Mary’s General Hospital, Milton, Portsmouth.
Physician,
REFERENCES C. J., JEFFREY, H. C. & LACKEY, R. W. (1951) E osinophilic granuloma of the lung. Report of two cases. U.S. arm. Foxes med. J. 2, 1085. GRANT, L. J. & GINSBURG, L. (1955) Eosinophilic granuloma (honeycomb lung) with diabetes insipidus. Lancet ii, 529. HOFFMAN, L., COHN, J. E. & GAENSLER, E. A. (1962) Respiratory abnormalities in eosinophilic granuloma of the lung. New Eagl. J. Med. 267, 577. KNUDSON, R. J., BADGER, T. L. & GAENSLER, E. A. (1966) Eosinophilic granuloma of the lung. FARINACCI,
Med. LEWIS,
Thorax
23,
248.
J. G. (1963) Eosinophilic granuioma and its variants with special reference to the lung involvement. Q. Jl Med. 33, 337.
A. R. Davidson LICHTENSTEIN, L. (1953) Histiocytosis X: integration of eosinophilic granuloma Siwe Disease and Schuller-Christian Disease as related manifestation entity. A.M.A. Archs Path. 56, 84. NADEAU, P. J., ELLIS, F. H., HARRISON, E. G. & FONTANA, R. S. (1960) Histiocytosis X. Dis. Chest 37, 325. PARKINSON, T. (1949) Eosinophilic xanthomatous granuloma with honeycomb
of
of bone, single
Primary
Letterernosologic pulmonary
Br. med. ‘J. i,
lungs.
1029. STANFORD, W., SPIVEY, C., LINDBERG, E. F. & ARMSTRONG, R. G. of the lung. Ann. thorac. Surg. 11, 299. WEBER, W. N., MARGOLIN, F. R. & NIELSEN, S. L. (1969) Pulmonary 18 patients with reports of six cases. Am. J, Roentgenol. 107,
(1971)
Eosinophilic
histiocytosis
280.
granuloma X.
A review
of
EOSINOPHILIC
GRANULOMA A. R.
King’s
OF THE LUNG
DAVIDSON
College Hospital,
London
Summary Pulmonary the remission
eosinophilic granuloma and relapse that may
diagnosed occur.
by lung
biopsy
is described;
the
case
demonstrates
Eosinophilic granuloma or histiocytosis X sometimes presents as a widespread infiltration of the lungs. In some cases this is accompanied by extra pulmonary changes, especially in bone. Pulmonary eosinophilic granuloma is rare. The first cases were described in 1951 (Farinacci et al. 1951). The clinical course is unpredictable. This report describes one case of a man who received no treatment and had a radiological remission lasting three years. Case Report A 27-year-old lorry driver had a tonsillectomy in October 1964 for recurrent tonsillitis; a small postoperative haemorrhage was easily controlled. A chest radiograph the following day showed ‘generalized miliary mottling’. At this time he was symptom-free. Readmission for investigation showed that he had a haemoglobin of 97 mg/lOO ml, white blood count 7200, ESR 20 mm, platelets 157 000 and prothrombin 100%. The urea and electrolytes were normal; serum calcium 9.6 mg/lOO ml. Liver function tests were normal. Total plasma proteins were 6.9 g/100 ml. Eight sputum examinations failed to reveal any acid-fast bacilli and sputum cultures were always negative. Bronchoscopy showed no abnormality. Bronchial biopsy showed normal bronchial mucosae. Scalene node biopsy was also normal and as no diagnosis had been reached at this stage a diagnostic lung biopsy was undertaken. At operation through a small left thoracotomy the lung surface was noted to be studded with small sago-grain-like nodules. The microscopic appearance of the lung showed granulomatous lesions which under high power showed an infiltration with many varieties of cells, including histiocytes, lymphocytes and plasma cells (Fig. l), all characteristic of eosinophilic granuloma of the lung. A skeletal survey at this time showed one lesion in the left parietal bone. No treatment was deemed necessary as the patient was symptom-free. He was reviewed regularly after discharge, remaining symptom-free. By April 1966 his chest radiograph had begun to clear and by March 1967 there was no abnormality on it and the left parietal lesion had also cleared. He remained well until March 1970, when he presented with pleuritic left chest pain, weight loss and shortness of breath on exertion. Physical examination was normal. A chest radiograph showed a recurrence of the diffuse miliary appearance, but there was now a lesion in the right third rib posteriorly and a recent cough fracture in his right fourth rib. He was thought to have widespread disease, and prednisone 20 mg/day was started. He made a good symptomatic recovery but with no change in his chest radiograph. Prednisone therapy was discontinued after six months : at this time he was symptom-free but the chest radiograph had not improved. Regular reviews as an out-patient showed no change clinically or radiologically. By March 1973 he had been followed for Sg years in all, and three years after radiological relapse, he was still
126
A. R. Davidson
Fig.
symptom-free the course insipidus.
2. Lung
biopsy
but the chest radiograph of his disease had he had
in eosinophilic
granuloma.
had not changed over the a spontaneous pneumothorax
H & E x 350.
last three years. or any symptoms
At
no time in of diabetes
DISCUSSION The term histiocytosis X was first used by Lichtenstein in 1953. He considered that the skeletal and soft tissue lesions represented various manifestations of the same disease, due to proliferating histiocytes (Lichtenstein 1953). The traditional terms are still in common use, they are eosinophilic granuloma for patient with bone lesions only, Hand-SchullerChristian syndrome for a chronic slowly advancing involvement resulting chiefly in symptoms from bones and Letterer-Siwe syndrome for children with a rapid visceral spread, often involving bone as well. Parkinson in 1949 predicted that eosinophilic granuloma would be found early in the lungs, but it was two years later that the first two cases of solitary eosinophilic granuloma of the lung, confirmed at biopsy, were described (Farinacci 1951). Since then it has been reported in increasing frequency and has become an important differential diagnosis of diffuse pulmonary infiltration, in one series accounting for 2.6% of all patients with miliary lung disease (Knudson et al. 1966). Primary pulmonary eosinophilic granuloma predominates in males, with a male to female ratio of 5 : 1. The usual age range is 15 : 20 years (Weber et al. 1969). The onset is insidious. The disease may be found on routine chest radiographs in symptom-free patients. Presenting symptoms are few and include cough, chest pain, shortness of breath and weight loss (Weber et al. 1969). Rarely patients may present later with severe dyspnoea and a chest radiograph of honeycomb lung (Grant & Ginsburg 1955). The diagnosis is made by open lung biopsy (Stanford et al. 1971) or drill biopsy.
Eosinophilic Granuloma of the Lung
127
There are two well recognized complications. Pneumothorax occurs in 20-30 o/o (Hoffman et al. 1962). In some cases the pneumothorax may be recurrent, needing surgical correction, and this recurrence may be explained by subcortical bleb formation (Knudson et al. 1966). Diabetes insipidus is reported in 21%. The pathology of this is unknown, but it may be due to some involvement of the hypothalamic-hypophyseal system (Hoffman et al. 1962). Most reported patients have been followed for a short period only, but there are reports of a few patients followed for up to nine years (Hoffman et al. 1962; Lewis 1963). It is known that the disease runs an unpredictable and usually benign course, occasionally with spontaneous remission (Nadeau et al. 1962). Our patient had no treatment when he first presented. He had a slow and complete radiological remission in both his chest and his skull. We have found no previous reports of eosinophilic granuloma of the lung relapsing after a remission. In this patient there was no obvious cause for the relapse. At this time he had chest pain, shortness of breath and weight loss. There is no agreed treatment of this condition. Radiotherapy gives excellent results when the lesion is limited to bone but seems contraindicated in pulmonary disease, as large doses will give rise to further pulmonary fibrosis and small doses are ineffectual (Nadeau et al. 1960; Hoffman et al. 1962). Corticosteroids are advocated early in the disease, but spontaneous remissions occur without therapy and there is no real evidence that they alter the natural course of the disease (Knudson et al. 1966). However, certain patients with symptoms may benefit from corticosteroid therapy (Stanford 1971) and certainly our patients rapidly became symptom-free with prednisone.
ADDENDUM
Since this report was prepared the patient has developed no new respiratory symptoms or signs. However, in October 1974 he presented with a short history of polyuria and polydipsia, which were found to be due to diabetes insipidus. This is now well controlled with lycine, vasopressin nasal spray and chlorpropamide.
ACKNOWLEDGEMENTS
This paper is published by kind permission of Dr J. H. Dadds, Consultant Saint Mary’s General Hospital, Milton, Portsmouth.
Physician,
REFERENCES C. J., JEFFREY, H. C. & LACKEY, R. W. (1951) E osinophilic granuloma of the lung. Report of two cases. U.S. arm. Foxes med. J. 2, 1085. GRANT, L. J. & GINSBURG, L. (1955) Eosinophilic granuloma (honeycomb lung) with diabetes insipidus. Lancet ii, 529. HOFFMAN, L., COHN, J. E. & GAENSLER, E. A. (1962) Respiratory abnormalities in eosinophilic granuloma of the lung. New Eagl. J. Med. 267, 577. KNUDSON, R. J., BADGER, T. L. & GAENSLER, E. A. (1966) Eosinophilic granuloma of the lung. FARINACCI,
Med. LEWIS,
Thorax
23,
248.
J. G. (1963) Eosinophilic granuioma and its variants with special reference to the lung involvement. Q. Jl Med. 33, 337.
A. R. Davidson LICHTENSTEIN, L. (1953) Histiocytosis X: integration of eosinophilic granuloma Siwe Disease and Schuller-Christian Disease as related manifestation entity. A.M.A. Archs Path. 56, 84. NADEAU, P. J., ELLIS, F. H., HARRISON, E. G. & FONTANA, R. S. (1960) Histiocytosis X. Dis. Chest 37, 325. PARKINSON, T. (1949) Eosinophilic xanthomatous granuloma with honeycomb
of
of bone, single
Primary
Letterernosologic pulmonary
Br. med. ‘J. i,
lungs.
1029. STANFORD, W., SPIVEY, C., LINDBERG, E. F. & ARMSTRONG, R. G. of the lung. Ann. thorac. Surg. 11, 299. WEBER, W. N., MARGOLIN, F. R. & NIELSEN, S. L. (1969) Pulmonary 18 patients with reports of six cases. Am. J, Roentgenol. 107,
(1971)
Eosinophilic
histiocytosis
280.
granuloma X.
A review
of
