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This paper is mainly intended to inform patients. Medical terms are explained in brackets so that patients who wish to learn these concepts can do so, in order (for example) to understand doctors’ reports and scientific literature.
The Papulosis atrophicans maligna (Köhlmeier-Degos disease) is a very rare illness. It was described for the first time by Köhlmeier in 1941 and documented as a distinct illness by Degos in the same year. Since then about 130 cases have been written up in scientific literature.
The characteristic skin changes of the Papulosis atrophicans maligna allow conclusive diagnosis. They begin as small erythematous (red) moles, commonly around the trunk and the upper extremities. After a few days the center of the lesion falls in, so older lesions show a porcelain-white atrophic (dead, sunk) centre with an erythematous (red) halo (outer ring)4. Characteristically it leaves the Palmae, Plantae, Capillitium and the Facies (face) untouched.
Age at which symptoms appear, family history
Symptoms normally appear between the age of 20 and 50. The illness usually occurs sporadically but on rare occasions it has affected several members of the same family.
Diagnosis of the Papulosis atrophicans maligna is usually decided clinically on the basis of the characteristic skin changes, and confirmed by histological (microscopic) examination. The laboratory tests are not by themselves conclusive, as coagulating disturbances may be present (see Etiology below).
Histology (Tissue Type)
Histologically the skin lesions typically show a wedge-shaped area of cutaneous ischaemie. The characteristic histological features with wedge-shaped tissue necrosis and thrombosis of the supplying blood vessels are not evident in all cases27. In one case report, Harvell examined the histology of the lesions in connection with their duration and postulated that early lesions can more closely resemble a Lupus of erythematodes due to their extended Muzin (deposits) in the dermis, and superficial as well as deep perivascular inflammation. Older lesions, on the other hand, bore more similarities to a minimal variant of the Lichen sclerosus et atrophicans, with their papillaere dermal sklerosis with Atrophie and Hyperkeratose28.
Etiology (Causes) of the illness:
The etiology (cause) of the illness is not yet known, and amongst other things genetic factors (transmission), auto-immunological processes (the immune system attacks its own body), an allergic vasculitis (blood vessel inflammation), an infectious agent (for example viruses or bacteria) and coagulopathiens (blood coagulation problems) have been proposed. There is a whole list of hypotheses, but none of them have yet been proven. A genetic predisposition has been suggested because cases of the Papulosis atrophicans maligna affecting several members of the same family are known. Within these families often members related in the first degree are affected, suggesting an autosomal dominant factor transmission151617.
Electron-microscopic evidence of intrazytoplasmatic paramyxovirus-similar inclusions has suggested an infectious etiology2130. Tests for paramyxovirus DNA from skin samples of patients with Papulosis atrophicans maligna by means of PCR gave negative results31. The crucial question must be whether the obliteration of the blood vessels in the affected skin areas results from a thrombosis in the context of a primary coagulopathy or whether it occurs as a consequence of a primary vasculopathy e.g. by release of tissue-active factors within the range of endothelium defects. There are no conclusive laboratory findings regarding the Papulosis atrophicans maligna. However, there are a relatively large number of reports of cases of patients with defects of the blood clotting system.
Drucker reports on a patient with increased thrombozyten aggregation on Adenosindiphosphat, Epinephrin, kollagen, Serotonin and Thrombin32. An increased thrombozyten aggregation has been recorded in other cases as well23.
Patients with Papulosis atrophicans maligna can exhibit the anticardiolipin antibodies and Lupus anticoagulans antibodies that accompany an increased thrombosis tendancy/susceptability1213. Also a lowered Fibrinolyse could be a cause of the capillary thrombosis in the lesions of the Papulosis atrophicans maligna. Black and others observed a complete loss of the fibrinolytic activity in the centres of the skin lesions and a reduction of the fibrinolytic activity in the peripheral blood11. With some patients an increased fibrinogen level was found2526. A degraded plasminogen level as well as increased activity of the plasminogen-activator inhibitors has also been documented in the context of the Papulosis atrophicans maligna21. There is (to date) one report of Papulosis atrophicans maligna in an HIV-infected homosexual man14.
Progression of the illness
The characteristic cutaneous (at the skin) efflorescences in most cases appear before the systemic (more than one organ is affected) effects of the disease occur. The illness can stay limited to the skin for many years, but if a systemic development occurs, close-knit medical control is needed, because serious problems can occur. Symptoms can result from ischemic complications (oxygen deficiency in the tissue caused by capillary blockages), where all organs can be affected, but the most serious aspects of the illness progression are above all intestinal (stomach and intestine) and central nervous system (brain) complications10.
The malignancy of the illness is shown by the fact that even after many years of purely cutaneous infection a systemic development can occur. The systemic manifestation can in many cases lead to grave complications after just a few months.
The most frequent serious complications are, in descending order, Peritonitis (inflammation of the abdominal linings), ZNS complications, pleurisy (inflammation of the lung membrane) and/or pericarditis (heart inflammation)10. The intestinal complications mainly affect the small intestine, with peritonitis frequently following an intestine perforation (intestine tear). Symptoms can be absent or be non-specific with abdominal pain, digestion problems etc. Neurological complications reported to date are consequences of cerebral vasculopathy (degeneration of the cerebral blood vessels) eg aspetic meningitis (non-bacterial inflammation of the brain membrane), enzephalitis (brain inflammation), radiculoneuritis (= nerve inflammation) and myelitis (backbone marrow inflammation)21. Implications for the eyes are rare, but can primarily involve the eyelids, the conjunctive (outer surface of the eye), retina and choroidea (blood vessel linings), and secondarily be neurological problems such as diplopy (double vision) and ophthalmoplegy (paralysis of the eye muscles).
Hypothesis: Do two forms of the illness exist? The malign and the benign forms?
Some patients may for many years, perhaps even lifelong, exhibit purely the cutaneous aspects of the disease. Many of these cases occur in families amongst relatives of the first degree. Cases of this at least in the long-term view “benign” effect are possibly not adequately documented, given that only lifelong observation of such patients can lead to a final evaluation of the seriousness of their illness. As a result it has not to date been clarified whether, alongside the serious “malignant” atrophic papulosis there is also a mild variant of the illness with purely cutaneous implications, and whether these two forms can clearly be differentiated from each other.
There is as yet no proven-effective treatment of the Koehlmeier Degos disease. Immunosuppressive therapy trials with, for example, cyclosporin A, azathioprin, cyclophosphamide and steroids show no significant success. Treatments aimed at achieving anti-coagulative (restraining coagulation) and perfusion-promoting (improving blood circulation) effects have in some cases produced a lessening of the skin symptoms and/or had morbostatic effects (delaying the progression of the illness), and this applies particularly to acetylsalicylic acid (ASS), and also to Dipyridamol, Ticlopidin and Heparin.
Vicktor et al. report for the first time on the successful treatment of a patient with the cutaneous form of the illness with Pentoxyfyllin 1200 mg/die p.o. and ASS 100 mg/die p.o., producing an almost complete retreat of the skin lesions5.
1 Köhlmeier W. (1941). Multiple Hautnekrosen bei Thrombangitis obliterans. Arch. Dermatol. Syph. 181, 783-792
2 Degos R., J. Delort, R. Tricot (1942). Dermatite papulosqameuse atrophiante. Bull. Soc. Fr. Derm. Syph. 49, 148-150
3 Snow J. L., S.A. Muller (1995). Degos Syndrome: malignant atrophic papulosis. Semin. Dermatol. 14, 99-105
4 Vazquez- Doval F.J., F.R. De Erenchun, J.A. Paramo, E. Quintanilla (1993). Malignant atrophic papulosis. A report of two cases with altered fibrinolysis and platelet function. Clin. Exp. Dermatol. 18, 441-444
5 Vicktor C., U. Schultz-Ehrenburg (2001). Papulosis maligna atrophicans (Köhlmeier-Degos). Hautarzt 52, 734-737
6 Farrell A. M., J. Moss, C. Costello, L.A. Fearfield, D. Woodrow, C.B. Bunker (1998). Br. J. Dermatol. 139, 708-712
7 Chave T.A., S. Varma, G.K. Patel, A.G. Knight (2001). Malignant atrophic papulosis (Degos’ disease): clinicopathological correlations. JEADV 15, 43-45
8 Sullivan G.W., H.T. Carper, W.J. Nowick, G.L. Mandell (1988). Inhibition of the inflammatory action of Interleukin-1 and Tumor Nekrosis Factor (alpha) on neutrophil function by Pentoxyfylline. Infect. Immun. 56, 1722-1729
9 Su W.P., A.L. Schroeter, D.A. Lee, T. Hsu, S.A. Muller (1985). Clinical and histologic findings in Degos syndrome (malignant atrophic papulosis). Cutis 35, 131-138
10 Atchabahian A., M.J. Laisne, F. Riche, C. Briard, J. Nemeth, P. Valleur (1996). Small bowel fistula in Degos’ disease: a case report and literature review. Am J Gastroenterol 91, 2208-2211
11 Black M.M., K. Nishioka, G.M. Levene (1973). The role of dermal blood vessels in the pathogenesis of malignant atrophic papulosis (Dego’s disease). Br J Dermatol 88, 213-219
12 Rocha H.E. (1985). Fibrinolysis in Dego’s disease. Thromb Haemostasis 54, 780
13 Daniel F., C. Foix, J.M. Gray et al. (1982). Papulose atrophiante maligne avec insuffisance de la fibrinolyse sanguine. Ann Dermatol Venerol 109, 763-764
14 Requena L., M.C. FarinaA. Barat (1998). Dego’s disease in a patient with acquired immunodeficiency syndrome. J Am Acad Dermatol 38, 852-856
15 Powell, Bordea, Wojnarowska, Farrell, Morris (1999). Benign familial Degos disease worsening during immunosuppression. Br J Dermatol 141, 524-527
16 Katz S.K., L.J. Mudd, H.H. Roenigk (1997). Malignant atrophic papulosis (Dego’s disease) involving three generations of a family. J Am Acad Dermatol 37
17 Kish L.S., D.P. Bruynzeel (1984). Six cases of malignant atrophic papulosis (Degos disease) occuring in one family. Br J Dermatol 111, 469-471
18 Thomson K.F., A.S. Highet (2000). Penile ulceration in fatal malignant atrophic papulosis (Degos disease). Br J Dermatol 143, 1320-1322
19 Metz J., A. Amschler, M. Henke (1980). Morbus Degos (Papulosis atrophicans maligna). Hautarzt 31, 108-110
20 Burg G, D. Vieluf, W. Stolz et al . (1989). Malignant atrophic papulosis. Hautarzt 40, 480-485
21 Olmos L., P. Laugier (1977). Ultrastructure de la maladie de Degos (rapport d’un noveau cas et revue de la litterature). Ann Dermatol Venereol 104, 280-293
22 Lee D.A., W.P.D. Su, T.J. Liesegang (1984). Ophthalmic changes of Degos’ disease (malignant atrophic papulosis). System Ophthalmol 91, 295-299
23 Stahl D., K. Thomsen, K. Hou-Jensen (1977). Dego’s disease treated with platelet-suppressive drugs. Lancet, July 2, 46-47 (letter to the editor)
24 Habbema L., L.S. Kish, T.M. Starink (1986). Familial malignant atrophic papulosis (Degos’ disease) – additional evidence for hereditary and benign course. Br J Dermatol 114, 134-135
25 Roenigk H.H., R.G. Farmer (1968). Degos’ disease (malignant atrophic papulisis): report of three cases with clues to etiology. JAMA 206, 1508-1514
26 Howsden S.M., S.J. Hodge, J.H. Herndon, R.G. Freeman (1976). Malignant atrophic papulosis of Degos: report of a patient who failed to respond to fibrinolytic therapy. Arch Dermatol 112, 1582-1588
27 Grilli R., M.-L. Soriano, M.-J. Izquierdo, M.-C. Farina, L. Martin, F. Manzarbeitia, L. Requena (1999). Panniculitis mimicking lupus erythematosus profundus. A new histopathologic finding in malignant atrophic papulosis (Degos’ disease). Am J Dermatopathol 21, 365-368