Acta med. scand. Vol. 184, pp. 165-169, 1968

KOHLMEIER-DEGOS’ DISEASE (MALIGNANT ATROPHIC PAPULOSIS)

Report of the First Scandinavian Case

Francis Benson and Frank Bergman

From the Departnient oj Pathology, University of Utried, Umed, and the Departments of Anesthesia and Intensive Care Unit, Centrallasarettet, Boden, Sweden

Abstract. A report is given of the first Scandinavian case of malignant atrophic papulosis (Kohlmeier-Degos’ disease) in a man aged 31. The patient presented the typical morphological changes in the skin and intestine. This case is the first in which similar vascular lesions have been demonstrated in the lungs, liver and pancreas.

In 1941 Kohlnieier (4) described a remarkable cutaneo-intestinal syndrome in a 21-year-old man and assumed the findings to be manifestations of thrombo-angiitis obliterans. In the following year Degos et al. (2) reported a similar case and thought the syndrome to be a well defined entity, which they first called papulo-squamous dermatitis, but afterwards malignant atrophic papulosis to indicate the poor prognosis of the condition.

A further 19 cases have since been published. The literature has been reviewed by Sidi et al. (7) and by Strole et al. (8).

The case reported below is the first known in- stance of this rare disease in Scandinavia. It is also the first case in which typical vascular lesions of Kohlmeier-Degos’ disease have ever been found in the lungs, liver and pancreas. The diagnosis was made at histological examination post mortem and historical data, particularly those relevant to the evolution of the cutaneous lesions, were far from complete.

CASE REPORT A man, aged 30, had mild pneumonia in 1962 and in 1963. In the summer of 1965 he had a rash on the trunk and thighs. Later (after the patient had died) the pa- tient’s wife described these lesions as red patches which afterwards became pale, first centrally, and then disap- peared. That year he also had diffuse epigastric pain but roentgenography revealed nothing remarkable. In August 1966 the symptoms increased, with frequent vomiting and considerable loss of body weight (20 kg within two

months). H e was admitted to his local hospital for in- vestigation. A few days after admission he had per- forating ulcer in the anterior part of the stomach, for which he was operated upon in October 1966. Careful abdominal palpation and examination revealed nothing remarkable apart from slight enlargement of the spleen. Chest X-ray after the operation showed diffuse coalescent densities on both sides (no abnormalities found at chest X-ray in 1964). H e was transferred to the Chest Clinic, Boden, for further investigation. H e had fever (38-39°C) for a week and on December 4, 1966, an acute attack of abdominal pain suggesting perforation. Surgical explora- tion revealed perforation of the ileum with considerable local changes for which the intestine was resected and anastomosed end-to-end. He was then transferred to the department for intense therapy.

On admission to that department a careful inquiry was again made into the patient’s history, this time including also a search for signs of intoxication and allergy, but revealed nothing of interest. The patient was very cachectic but otherwise in a good general condition. Chest X-ray showed further progression of the densities in both lungs. The densities were partly coalescent but here and there they were rounded and well defined and appeared malignant. ESR 30 mm/h, H b 11.1 g/lOO ml, R.B.C. 4 milI., Hct 38%, platelet count 272,000; W.B.C. 8300 n,ith 76% neutrophils. Serum electrolytes: normal. Serum protein 4.4 g/lOO ml. Electrophoresis: albumin 44%, alpha,-globulin 10.8 % , alpha,-globulin 14.9 % , beta-glob- ulin 15.9%, and gamma-globulin 14.1 % . Plasma creati- nine 0.7 mg/100 ml. Urine salts, specific gravity and osmolarity normal. Urine sediment 2-3 red blood cells, 5-10 white blood cells, only few bacteria. Sternal punc- ture: markedly increased myelopoesis with shift to the left and dominated by myelocytes. Increased number of mature plasma cells. Reticulum markedly increased. In- creased alkaline phosphatase activity of neutrophils.

Culture of throat swabs, bronchial secretion, urine and blood was repeatedly negative. Repeated examination for mycobacteria with microscopic examination, culture and guinea-pig inoculation negative. Culture and agglutination for pseudotuberculosis negative. Antistreptolysin titre 70 units per ml, antistaphylolysin titre 0.36 unit per ml. No agglutination of Salmonella 0-antigen, H-antigen, Bru- cella abortus or Tularense. Bronchoscopy with biopsy and

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166 F . Benson and F. Bergman

cytological examination revealed nothing remarkable. Because of his cachectic condition the patient was

given adequate nutrition parenterally. Tuberculosis was strongly suspected and treatment with PAS, INH and streptomycin was started on December 7. Fever persisted (38-39°C) and cardiac frequency was high, 120-130. ECG normal except for tachycardia. On December 10 the body temperature rose still more (41°C) and a chest X-ray showed progression of the changes, besides which the liver was palpably enlarged. PAS was therefore with- drawn. On December 14 he again had peritonitis and was again subjected to surgical exploration. No perfora- tion was found but the small bowel showed marked changes with fibrin-coated lesions and a considerable amount of whitish, round infiltrates with palpable thicken- ing of the serosa. A small part of the ileum was excised. The patient tolerated the operation fairly well. Micro- scopical examination of the material obtained at the operations yielded no information of diagnostic value.

The operative specimens were roughly 10 cm long seg- ments of the ileum with diffuse thickening of the wall and numerous pale-gray to yellow irregular plaques on the serosal surface. Centrally there was a perforation, the si7e of a peppercorn, and an adjacent circular stric- ture. The mucosal folds were exaggerated.

Microscopically the perforation was lined by thick fibrinous-necrotic masses and bordered by granulation tissue with abundant inflammatory cells, mainly granu- locytes. Adjacent submucosa was oedematous with dilated vessels and mild fibrosis. The middle-sized arteries showed subendothelial fibrosis with marked narrowing of their lumina. Some areas of the serosal surface were covercd by a thin fibrin coat with an admixture of granulocytes and single fungi of the species Candida dbicatis.

The pathological diagnosis was infarction of the ileum of obscure origin with perforation and peritonitis. In retrospect, the lesions were identical with those described and illustrated under necropsy findings.

One week after the operation the patient had chills and intense parenteral treatment with penicillin (4 mill. units per hour) was tried with simultaneous steroid therapy to suppress the pulmonary reaction. For a few days the fever disappeared, but tachycardia persisted. On December 28 he had symptoms of a new perforation. Explorative surgery revealed a palm-sized perforation of the stomach and severe peritonitis. The lesion was closed with a fairly satisfactory result. The patient made a good recovery but had high grade fever and tachycardia. At operation tracheotomy was done and even after the opera- tion the patient could not manage without a respirator. As before, new laboratory and bacteriological tests proved negative. The serum bilirubin and transaminases gradu- ally increased and the patient developed a bleeding tendency with an Ivy bleeding time of more than 36 min. The plastic clotting time was normal. Fibrinolytic activity with fibrinolysis 0.2 mg/ml/h and fibrinogenolysis 0.31 mg/rnl/h, fibrinogen 0.15 g/lOO ml. He was given trans- fusions of fresh blood and EACA, which resulted in normalisation of these values and his bleeding time. On January 1, 1967, treatment with erythromycin was tried because of a period of high grade fever and further

progression of the pulmonary changes. The response was favourable: the fever disappeared and for the first time the pulse rate became normal, and the patient’s general condition improved. Within a few days the pulmonary changes regressed considerably. After four days the serum bilirubin began to rise rapidly, the liver increased further in size, tachycardia returned and body temperature rose. Erythromycin was withdrawn and other antibiotics were tried but without effect. On January 9 he was treated with hypothermia with fair success until January 13, when the patient went into irreversible shock and died on January 16.

Necropsy jindings Complete necropsy, including the brain, was performed at Centrallasarettet, Boden. The external examination re- vealed jaundice and generalised petechial cutaneous haemorrhages. The chief finding was fibrinopurulent pe- ritonitis with widespread adhesions and a right-sided sub- diaphragmatic abscess. The gastrointestinal tract was di- lated and the content heavily bloodstained. The intestinal serosa was covered by thick patches of pus and the intestinal wall was oedematous. The mucosa of the stomach and small intestine was thickened, oedematous and showed widespread haemorrhages. The middle of the dorsal wall of the stomach had a 1.5 x 1.5 cm perfora- tion coalesced with the left liver lobe.

The mesenteric lymph nodes were enlarged. The mesenteric vessels were dissected but no nodules, thrombi or other gross changes were found.

The liver showed well defined haemorrhagic infarcts. No gross changes were seen in the large trunks of the hepatic artery or portal vein.

Other autopsy findings were scattered small necroses in pancreas, tracheobronchitis and multiple haemorrhagic pulmonary infarctions up to the size of almonds. No thrombi were seen in the main branches of the pulmonary artery.

Microscopical srudy of the operative specimens and specimens obtained at autopsy showed largely uniform pathological appearance of affected vessels in the gastro- intestinal tract, liver, pancreas and lungs. The typical picture consisted of intravascular endothelial proliferation and progressive occlusive fibrosis in small and medium- sized arteries (Figs. 1-4) with or without secondary thrombosis and consequent ischaemic infarction.

The lesions in the gastrointestinal tract, from the stomach through colon, were of uniform appearance and involved all the layers of the intestinal wall. The sub- mucosa was affected most with severe congestion and oedema. The blood and lymph vessels were dilated and often surrounded by fibrous tissue. The arterial walk were irregularly thickened, hyalinised and encircled by a few lymphocytes. The disorganisation was due to an eccentric subendothelial fibrosis with preserved elastica interna leading to occlusion of small vessels and to re- duction in the size of the lumina of larger vessels. Thrombi of various ages and sizes were adherent to the vessel walls. Veins were also affected though to a lesser degree. Occasionally, though rarely, a few areas of active vasculitis were recognized with involvement of the vessel wall by lymphocytes, histiocytes and some neutrophils.

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Kohlmeier-Degos’ disease 167

Fig. 1. Submucosal artery in ileum (operative specimen) with marked subendothelial fibrosis. Haematoxylin-eosin, x 100.

Fig. 2. Same section as in Fig. 1. Internal elastic lamella intact. van Cieson-elastica, x 100.

Fig. 3 . Submucosal artery in ileum. Marked subendo- thelial fibrosis and mild lymphocyte reaction in sur- rounding stroma. Haematoxylin-eosin, x 100.

Fig. 4 . Same section as in Fig. 3. Internal elastic lamella intact. van Gieson-elastica, x 100.

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168 1;. Benson and I;. Bergrnan

DISCUSSION Kohlmeier-Degos’ disease, papulosis atrophicans maligna, is a remarkable systemic disorder of the vessels. It is characterised by practically pathog- nomonic skin lesions. The gastrointestinal tract is the most often affected of the organ systems in- volved and the outcome is generally fatal owing to multiple intestinal infarctions with perforations and consequent fulminating peritonitis. The cause of the disorder is obscure and no effective treat- ment is yet available. Clinically the disease is readily distinguished from polyarteritis nodosa and thrombo-angiitis obliterans and from a patho- logical point of view it cannot be regarded as a manifestation of these diseases.

The cases on record were seen in 17 men and two women. The commonest age of onset is 15 to 25 years. The disorder is usually fatal within one year of the appearance of the skin lesions.

The initial skin lesions, which are scattered over the trunk, neck and proximal portions of the limbs, develop slowly. The lesions are asympto-

Fig. 5 . Pulmonary infarction with two small arteries al- most occluded by loose subendothelial fibrosis. van Cieson-elastica, x 85.

The mucosa showed patches of necrosis with ulcera- lions and splitting of the muscularis mucosae. In severely affected areas and around the large perforation in the stomach all layers of the wall were infarcted and showed signs of superimposed infection with abundant inflam- matory cells, mainly neutrophilic leucocytes and some fungi of the species Candida albicans.

Other segments of the intestine showed vascular changes also in muscularis propria and some fibrous tissue was deposited in both muscle layers. There was abundant fibrinopurulent exudate on the serosal surface and in the subserosal connective tissue.

The mesenteric lymph nodes showed non-specific in- flammation and no vascular changes.

Lesions identical with those in the gastrointestinal tract were seen in small blood vessels in the lungs (Fig. 3, liver and pancreas (Fig. 6). The liver and pancreas showed widespread haemorrhagic necroses with well de- fined leucocytic margins. The liver surface was covered with thick patchy layers of fibrin containing numerous granulocytes. Also the infarcted pulmonary parenchyma showed abundant granulocytes and the adjacent lung tissue was covered by haemorrhagic pneumonia without any histologically demonstrable microorganisms. The Fig. 6. Eccentric, subendothelial fibrosis of medium-sized visceral pleura was fibrously thickened and its surface artery in pancreas. Adjacent parenchyma is partly necrotic was partly covered by fibrin swarming with leucocytes. and shows scattered round cells. van Gieson-elastica,

hTo morphological changes were found in the brain. x 85 .

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Kohlmeier-Degos’ disease 169

matic, pink to red, rounded or oval papules. Within a few days they become umbilicated, and there appears a porcelain-white atrophic centre, encircled by a slightly elevated erythematous tele- angiectatic border. Some weeks later the lesions begin to disappear and leave behind atrophic white spots, but lesions in different stages of de- velopment can always be found.

Histopathologically the picture of the skin eruptions is that of necrosis in dermis and sub- cutaneous tissue with underlying oedema and a non-specific inflammatory reaction which is fol- lowed by sclerotic atrophy in the dermis and atrophy and hyperkeratosis of the epithelium. These lesions are the result of focal changes of small and medium-sized arteries in the subepi- dermal tissues with progressive subendothelial oc- clusive fibrosis with consequent ischaemic in- farcts. Veins and lymphatics are affected later by peripheral fibrosis. The skin and small bowel are the commonest sites of the spotty vascular changes and the abdominal symptoms are as a rule ushered in by the skin lesions. The onset of the abdominal symptoms generally marks the beginning of steady deterioration with a fatal issue. As long as the bowel is only slightly affected the patient generally feels well except for mild abdominal symptoms and fair loss of weight. Progression of the in- testinal lesions is accompanied by ileus, nausea, haematemesis and melena but an acute attack of intense epigastric pain may be a sign of the initial stage of the abdominal syndrome.

Morphologically the intestinal lesions do not differ from the cutaneous lesions, but the vascu- litis, thrombosis and adjacent inflammation are often more prominent in the intestine than in the skin.

Contrary to what was supposed on the basis of the first cases published, the disease is not con- fined to the skin and/or intestines. Thus identical focal vascular changes damaging the tissue have been described in the brain, kidney, heart, eyes, mesentery and bladder ( 1 , 3, 5, 6 , 7, 8, 9). This paper is the first to report similar vascular changes in the lungs, liver and pancreas. Such lesions may, perhaps, be found also in other organs, and possibly early enough to provide a clue to their aetiology.

REFERENCES I. Culicchia, C. F., Gol, A. & Erickson, E. E.: Diffuse

central nervous system involvement in papulosis atro- phicans maligna. Neurology (Minneap.) 12: 503, 1962.

2. Degos, R., Delort, J. & Tricot, R.: Dermatite papulo- squameuse atrophiante. Bull. SOC. franG. Derm. Syph. 49: 148, 1942.

3. Gever, S. G., Freeman, R. G. & Knox, J. M.: Degos’ disease (papulosis atrophicans maligna): report of case with degenerative disease of the central nervous system. Sth. med. J. (Bgham., Ah.) 55: 56, 1962.

4. Kohlmeier, W.: Multiple Hautnekrosen bei Trombo- angiitis obliterans. Arch. Derm. Syph. (Berl.) 181: 783, 1941.

5 . Naylor, D., Mullins, J. F. & Gilmore, J. F.: Papulosis atrophicans maligna (Degos’ disease): report of first United States case and review of literature. Arch. Derm. 81: 189, 1960.

6. Nomland, R. & Layton, J. M.: Malignant papulosis . .

with atrophy (Degos): fatal cutaneointestinal syn- drome. Arch. Derm. 81: 181, 1960. Sidi, E., Reinberg, A., Spinasse, J. B. & Hincky, M.: Lethal cutaneous and gastrointestinal arteriolar throm- bosis (malignant atrophying papulosis of Degos). J.A.M.A. 174: 1170, 1960. Strole, W. E. Jr., Clark, W. H. Jr. & Isselbacher, K. J.: Progressive arterial occlusive disease (Kohlmeier- Degos). A frequently fatal cutaneosystemic disorder. New Engl. J. Med. 276: 195, 1967. Winkelmann, R. K., Howard, F. M. Jr., Perry, H 0. & Miller, R. H.: Malignant papulosis of skin and cerebrum: A syndrome of vascular thrombosis. Arch. Derm. 87: 54. 1963.

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