Thorax 1991;46:851-853 851

Short reports Thorax: first published as 10.1136/thx.46.11.851 on 1 November 1991. Downloaded from

Diffuse pulmonary Case report A six year old black girl presented with angiomatosis haemoptysis (100 ml) and a chronic, non- productive cough of two years' duration. She had no other symptoms. The family history was non-contributory. Physical examination G J Canny, E Cutz, I B MacLusky, showed a well nourished patient in no acute H Levison distress. Her temperature was 38-5°C, pulse 84/min, blood pressure 120/80 mm Hg, and respiratory rate 24/min. She was not cyanosed Abstract but had finger clubbing and crackles over the A six year old girl with diffuse pulmonary lower lung fields. A chest radiograph showed a angiomatosis presented with haemo- diffuse interstitial infiltrate and blunting of the ptysis and diffuse interstitial changes costophrenic angles (fig 1) but normal cardiac with bilateral pleural effusions on the size and no hilar lymphadenopathy. A tenta- chest radiograph. The lung lesion as seen tive diagnosis of pulmonary haemosiderosis on biopsy specimens (and confirmed at (primary or secondary) was made. necropsy) consisted of bloodless, thin Investigations The haemoglobin concen- wailed, endothelium lined channels, tration was 117 g/l, the white cell count affecting the interstitial septae, pleura, 12 x 109/l with a normal differential, the bronchi, and adventitia of large vessels. platelet count 140 x 109/1, and the eryth- There was no response to oral cortico- rocyte sedimentation 6 mm in one hour. steroids or a trial of cyclosphamide. This Serum electrolyte, urea, and creatinine con- lesion may be an example of an angio- centrations and a coagulation profile were nor- genic disease. mal and urine analysis gave normal results. Serological tests (for antinuclear factor, rheumatoid factor, and antiglomerular base- Benign proliferation of the pulmonary vas- ment membrane antibodies) gave negative http://thorax.bmj.com/ cular tissue is a rare lesion, which usually results. An electrocardiogram and echocar- presents as a solitary nodule-that is, a benign diogram were normal. A sweat test and a haemangioma.' Diffuse pulmonary haeman- tuberculin (purified protein derivative, 5 TU) giomatosis, characterised by proliferation of skin test gave negative results. Cytological blood filled vascular spaces, is even less com- examination of sputum showed occasional mon. This entity has been described mainly in haemosiderin laden macrophages, but no acid neonates as part of a generalised process affect- fast bacilli were identified. Pulmonary func-

ing the skin, mucous membranes, and visceral tion studies showed a restrictive ventilatory on September 23, 2021 by guest. Protected copyright. organs ("miliary haemangiomas").23 A variant defect (forced vital capacity (FVC) 56% of this condition, in which the endothelium predicted, forced expiratory volume in one lined spaces contain no blood, has been second (FEV1) 59% predicted; FEV1/FVC referred to as "angiomatosis" (hamartomatous ratio 88%). An open lung biopsy was per- haem-lymphangiomatosis) by Koblenzer et formed in the hope of obtaining a definitive al.4 These authors used the term "angioma- diagnosis. This showed pronounced thicken- tosis" in view of the uncertain histological ing of the pleura and pulmonary septa by origin of the abnormal vascular channels. fibrous tissue with an abnormal proliferation There are only a few reported cases of of empty vascular channels throughout the haemangiomatosis affecting the lung tissue lung. These channels, which were lined with a primarily. Rowen et al5 described three cases single layer of endothelial cells, had variable Department of of diffuse "cavernous" haemangiomatosis of amounts of fibrous tissue and irregular Paediatrics the lung, and a 12 year old boy with mixed bundles of smooth muscle in the walls. Areas G J Canny capillary and cavernous haemangiomatosis of of haemorrhage, intra-alveolar oedema, and I B MacLusky was et were H Levison the lung reported by White al.6 We aggregates of chronic inflammatory cells describe a six year old girl who died of a noted within the pulmonary parenchyma, and Department of Pathology diffuse vascular proliferative lesion, largely pulmonary macrophages stained positively for E Cutz confined to the lungs and pleura and not iron. The pathological findings were thought Hospital for Sick associated with cutaneous lesions. Although in to be consistent with a diagnosis of diffuse Children, 555 clinical presentation, radiological findings, and pulmonary lymphangiomatosis or haemangio- University Avenue, fatal outcome our case resembles those repor- Toronto, Ontario, matosis. Canada M5G 1X8 ted by Rowen et al,5 the histological Subsequent course The patient was treated our 3 Reprint requests to: appearance of patient's pulmonary lesion with oral corticosteroids (prednisone mg/kg/ Dr Canny was that of angiomatosis as the abdominal day) for 10 weeks. She developed a persistent Accepted 7 June 1991 vascular spaces appeared empty. cough, daily haemoptysis, and considerable 852 Canny, Cutz, MacLusky, Levison

Figure I Chest Microscopically, the abnormal vascular radiograph showing a proliferation seen in lung biopsy specimens diffuse interstitial infiltrate Thorax: first published as 10.1136/thx.46.11.851 on 1 November 1991. Downloaded from and pleural effusions. was present in all sections of both lungs. These thin walled, endothelium lined chan- nels with empty lumina were most prominent in the subpleural regions and the pulmonary septa and particularly in the pulmonary hila, where they appeared in the adventitia of the pulmonary arteries and veins (fig 2). Focal clusters of loosely arranged spindle cells were observed in the periadventitial tissue (fig 2, insert). Immunohistochemical studies on these cells showed staining for vimentin and actin (markers of mesenchymal cells), with only occasional cells positive for factor VIII (a marker for endothelial cells). These abnormal channels were also seen in the walls of the bronchi, extending to the basement mem- brane of the respiratory epithelium. Areas of pulmonary oedema and haemorrhage were noted. Both pleural cavities contained blood, and extensive fibrous adhesions were present. Abnormal vascular proliferation was also exercise intolerance over this time. The found in the mediastinum, the pericardium, pleural effusions increased in size, and severe and the adventitia of the great arteries and in restrictive lung disease developed (FVC 24% the peripancreatic adipose tissue. predicted). Corticosteroids were discontinued, and she was given a four day course of cyclo- phosphamide (1 mg/kg/day) intravenously. She developed severe respiratory distress after Discussion of the two weeks, however, with an increase in the Our patient had diffuse angiomatosis right pleural effusion on the chest radiograph. lung, mediastinum, pericardium, great vessels, She subsequently died of respiratory failure. and peripancreatic adipose tissue. The non- is as it Necropsyfindings A postmortem venogram committal term "angiomatosis" used whether this lesion was performed in an attempt to discover the was not entirely clear origin of the abnormal vascular channels. This originated from the haematogenous or the showed normal distribution of barium into the lymphatic system. Within the lungs the large pulmonary veins, and microscopically angiomatous lesions primarily affected the http://thorax.bmj.com/ and the walls of the injected barium was seen within veins, pleura, the interlobular septae, venules, and capillaries in the expected loca- the bronchi, pulmonary arteries, and veins. accounts the substantial tions. The abnormal vascular spaces were This distribution for devoid of barium, however, indicating that interstitial infiltrate and pleural thickening seen The process they were not connected to the venous system. radiographically. angiomatous was non-malignant in nature, and there was no inherited basis for the condition.

Several reports23 have described young on September 23, 2021 by guest. Protected copyright. infants with diffuse haemangiomas, affecting mucocutaneous surfaces as well as multiple internal organs. The prognosis for such infants is generally poor because ofthe development of complications-for example, congestive heart failure, consumptive coagulopathy, severe bleeding, and compression of vital organs. Rowen et al5 described three children (2.5-7 years of age) with diffuse haemangiomatosis of

t~~~~~~~~~~~~f the lungs and pleura without concomitant skin lesions. In these patients the clinical and radiographic findings were virtually identical to those in our case and, despite systemic cortico- steroid treatment, they died of their disease *n-,-t.t.S';< -'iff ..s ...... ;...... LXA . ,; ,.i;< several years after diagnosis. The histopatho- logical findings in our case, however, differed A,~~~~~~ ~ ~ ~ ~ ~ ~ ~ somewhat from those described by Rowen et a15 in that the abnormal channels contained no LdtV,l~~~~~~~~~~w blood-that is, a haemangiomatous component was absent. Rowen et al' suggested that, once a Figure 2 Low magnification view of an area of interolobular septum between alveolar malignant process has been excluded, the com- tissue (Alv) and the pulmonary artery (PA) wall. The septum is expanded with bination of diffuse interstitial lung disease and irregularly shaped channels with empty lumina. A focal area of spindle cell proliferation bloody pleural effusions in a child is patho- is located near pulmonary artery (arrow). (Haematoxylin and eosin). Inset Close up ofspindle cells around the aventitia of the pulmonary artery. (Haematoxylin and gnomonic of pulmonary haemangiomatosis. eosin). Diffuse pulmonary haemangiomatosis and Diffusepulmonaryangiomatosis 853

angiomatosis need to be differentiated from Whether more patients with pulmonary pulmonary capillary haemangiomatois, seen in haemangiomatosis will benefit from such treat- older children and adults.78 The latter is ment remains to be seen. Thorax: first published as 10.1136/thx.46.11.851 on 1 November 1991. Downloaded from characterised by proliferation of capillary sized In summary, diffusepulmonary angiomatosis channels that infiltrate the lung interstitium and is a rare clinical entity with an extremely poor the walls of vessels and airways and leads to prognosis. The possibility of this condition death from progressive pulmonary hyperten- should be considered in a child with diffuse sion. Although the exact cause of these pul- interstitial lung disease associated with increas- monary vascular disorders is not clear, it has ing bloody pleural effusions. been suggested that they may represent an angiogenic disease-that is, lesions arising We thank J Chay for secretarial assistance. from non-neoplastic microvascular prolifera- tion.679 The concept of angiogenic disease is 1 Goorwitch J, Madoff F. Capillary hemangioma of the lung. based on the discovery and characterisation of Dis Chest 1955;28:98-103. 2 Burman D, Mansell PWA, Warin RP. Miliary haeman- several angiogenic polypeptides that can giomata in the newborn. Arch Dis Child 1967;42:193-7. stimulate or inhibit capillary growth and dif- 3 Holden KR, Alexander F. Diffuse neonatal heman- giomatosis. Pediatrics 1970;46:411-21. ferentiation.9 4 Koblenzer PJ, Bukowski MJ. Angiomatosis (hamar- Several therapeutic strategies have been tomatous hemlymphangiomatosis): report of a case with attempted in diffuse haemangiomatosis. diffuse involvement. Pediatrics 1961;28:61-76. 5 Rowen M, ThompsonJR, Williamson RA, Wood BJ. Diffuse Although corticosteroids have been reported to pulmonary hemangiomatosis. Radiology 1978;127: shrink haemangiomas," this approach was 445-51. 6 White CW, Sondheimer EM, Crouch EC, Wilson H, Fan unsuccessful in our patient, as in the cases of LL. Treatment of pulmonary hemangiomatosis with pulmonary haemangiomatosis described by recombinant interferon alfa-2a. N Engl J Med others.'51 Radiotherapy may also cause regres- 1989;320:1197-200. 7 Langleben D, Heneghan JM, Batten AP, et al Familial sion of haemangiomas,'2 but this approach was pulmonary capillary hemangiomatosis resulting in pul- not considered feasible in our patient in view of monary primary hypertension. Ann Intern Med 1988;109: 106-9. severe restrictive lung disease. Similarly, dif- 8 Tron V, Magee F, Wright JL, Colby T, Churg A. Pulmon- fuse pleural lesions precluded lung transplan- ary capillary hemangiomatosis. Human Pathol tation as a therapeutic option. A trial of cyclo- 1986;17:1 144-9. 9 Folkman J. Successful treatment ofan angiogenic disease. N phosphamide treatment was embarked on, in Engl J Med 1989;320:1211-2. view of a previous report'3 attesting to its 10 Fost NC, Esterly NB. Successful treatment of juvenile hernangiomas with prednisone. J Pediatr 1968;73:351-7. effectiveness in disseminated life threatening 11 Hurwitz CH, Greenberg SH, Song CH, Gans SL. Heman- vascular tumours. Unfortunately, this giomatosis of the pleura with hemorrhage and dissemin- approach was unsuccessful, possibly because ated intravascular coagulation. J Pediatr Surg 1982;17: 73-5. the beneficial effects of cyclophosphamide in 12 Kasabach HH, Merritt KK. Capillary hemangioma with these circumstances do not materialise for extensive purpura. Am J Dis Child 1940;59:1063-70.

13 Hurwitz CH, Alkalay AL, Sloninsky L, Kallus M, http://thorax.bmj.com/ several weeks and repeated courses of cyclo- Pomerance JJ. Cyclophosphamide therapy in life- phosphamide may be necessary.'3 In recent threatening vascular tumors. J Pediatr 1986;109:360-3. reports a therapeutic response to interferon, an 14 White CW, Wolf SJ, Korones DN, Sondheimer HM, Tosi MF, Yu A. Treatment ofchildhood angiomatous diseases antiproliferative agent, was obtained in three with recombinant interferon alfa-2a. J Pediatr children with pulmonary haemangiomatosis.6' 4 1991;1 18:59-66.

Thorax 1991;46:853-854 on September 23, 2021 by guest. Protected copyright. widely recognised as one of them. Several Achilles tendon patients with chronic airflow obstruction attending our hospital clinics were noted to rupture: an underrated have non-traumatic Achilles tendon ruptures while having long term oral corticosteroid complication of treatment. We have reviewed our clinic population and found that during 12 years 10 corticosteroid treatment patients had an Achilles tendon rupture related to steroid treatment.

D M Newnham, J G Douglas, J S Legge, Details of the patients J A R Friend Details of the 10 patients and their episodes of tendon rupture are given in the table. Their mean age was 68-5 years and in every case the Abstract rupture occurred while they were walking on Thoracic Medicine Ten patients attending outpatient clinics level ground. Rupture was diagnosed in five Unit, Aberdeen Royal who were taking oral corticosteroids patients immediately after the sudden onset of Infirmary, Aberdeen ruptured their Achilles tendon in the pain in the Achilles tendon with local tender- AB9 2ZB course 12 It that D M Newnham of years. is suggested ness, swelling, and a palpable discontinuity Achilles tendon is a J G Douglas rupture complica- that was sometimes visible. Extensive sub- J S Legge tion of corticosteroid treatment. J A R Friend cutaneous bruising developed around the Reprint requests to: ankle and extended over the dorsum of the Dr Friend Oral corticosteroid treatment has many side foot within hours. The remaining patients Accepted 18 July 1990 effects but Achilles tendon rupture is not presented some weeks after the onset of