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Ophthalmic Changes of Degos' Disease (Malignant Atrophic Papulosis)
Systemic Ophthalmology
Ophthalmic Changes of Degas' Disease (Malignant Atrophic Papulosis) DAVID A. LEE, MD,* W. P. DANIEL SU, MD,t THOMAS J. LIESEGANG, MD*
Abstract: A 49-year-old woman with typical skin lesions of Degas' disease was found to have an afferent pupillary defect, and altitudinal field loss. This loss was probably secondary to vascular occlusion in the optic nerve of a patient with a congenital anomalous retinal vascular pattern. The patient has had no other systemic involvement after a follow-up of 4 years. Three other patients seen in the past had eye involvement and involvement of the central nervous system and died between 1 and 16 years of the diagnosis. Multiple ocular manifestations of Degas' disease have been reported affecting the eyelids, bulbar conjunctivae, retina, and choroid in varying degrees. Diplopia, visual field defects, ophthalmoplegia, ptosis, papilledema, and optic atrophy are ocular changes secondary to involvement of the central nervous system. [Key words: conjunctival changes, Degas' disease, dermatologic changes, malignant atrophic papulosis, ocular changes, retinal changes.] Ophthalmology 91 :295-299, 1984
Degas' disease (malignant atrophic papulosis) is a rare disease of unknown cause which affects multiple organ systems in the human body. It was first described by Kohlmeier 1 in 1941 and further delineated by Degas et al 2 in 1942. It is characterized by an almost pathognomonic, asymptomatic, papular cutaneous eruption on the trunk and extremities that evolves to lesions, with atrophic porcelain-white centers surrounded by an erythematous telangiectatic border varying from 2 to 10 mm in diameter. Similar lesions have been described in patients with systemic lupus erythematosus. 3•4 Multiple ocular manifestations may occur with this disease. Recently, we saw a patient with optic nerve disease and an abnormal retinal vascular pattern that is probably related to this disease. We also reviewed the ocular features of other patients whom we have seen with Degas' disease.
From the Departments of Ophthalmology* and Dermatology,t Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Reprint requests to DA Lee, MD, cto Section of Publications, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
CASE REPORT A 49-year-old woman was seen at the Mayo Clinic in November 1977, complaining of asymptomatic, scattered, generalized, small pink papules with white centers. The skin lesions began to develop in 1970 and seemed to become more numerous with exposure to excessive sunlight, although the patient also noticed that new lesions developed without sun exposure. She complained of frequent feelings offainting, fatigue, palpitations, decreased exercise tolerance, anorexia, and loss of weight during the past year. She had noted pains in her neck, lower back, left hip, and left shoulder; numbness in her left hand; and decreased vision with a black spot in her right eye. Review of symptoms was positive for epigastric pain lasting 30 minutes to 2 hours after eating, but she had no nausea, vomiting, hematemesis, melena, or loose stools. Family history was noncontributory. On physical examination, the patient's vital signs were normal. Examination of the skin revealed discrete papular lesions 2 to 3 mm in diameter with porcelain-white depressed centers and erythematous borders (Fig l, top left). The skin lesions were in various stages of activity and were distributed over the upper and lower extremities, trunk, and the soles and dorsa of the feet. A skin biopsy specimen from the left buttock showed a wedge-shaped infarction of the upper dermis (Fig l, top right)
295
Fig 1. Top left, papules of Degos' disease, showing porcelain-white depressed centers and erythematous borders. Top right, skin biopsy specimen showing a wedge-shaped infarction in the upper dermis. (Hematoxylin and eosin X25.) Center left, fundus photograph showing right optic disc with vascular tortuosity and cilioretinal arteries which anastomose to retinal arteries at the disc and again peripheral to the disc. Note optic disc pallor inferotemporally. Center right, fundus photograph showing left optic disc with congenital tortuous vessels. Bottom left, typical telangiectatic conjunctival lesion seen in Degos' disease.
with lymphocytic infiltration perivascularly and fibrinoid necrosis of the blood vessel walls. No thrombosis was seen. A moderate deposit of mucin was present in the upper dermis, especially in the area of infarction. The clinical and histopathologic features of the skin lesions were considered to be diagnostic of Degos' disease. Direct immunofluorescence study of a skin specimen from the left thigh showed deposit of IgM in the superficial and deep blood vessels, consistent with vasculitis. Because of the patient's postprandial discomfort, upper gastrointestinal, stomach, esophagus, and duodenum roentgenographic studies were performed; all results were normal. Findings on a sigmoidoscopic examination to 17 em were normal, except
296
for mild internal and external hemorrhoids. Results of electromyography, sensory, and motor conduction studies of the left hand were normal. The ophthalmologic history was negative, except for a dark scotoma in the right eye, which had developed during the 6 months before examination at the Mayo Clinic. Visual acuity was 20/40 in the right eye and 20/25 in the left eye. The right eye had an afferent pupillary defect, and the left pupil was normal. Extraocular movements were full in both eyes. Slitlamp examination revealed no abnormality in either eye. Intraocular pressures were 14 mmHg in each eye. Fundus examination of each eye revealed marked tortuosity of both ar-
LEE, et al •
OPHTHALMIC CHANGES OF DEGOS' DISEASE
18
1000
20
Vos 2s
20
Voo 40
Fig 2. Visual field examination showing a superior altitudinal defect in right eye.
terioles and venules, particularly on the disc and in the area between the disc and the macula (Fig 1, center). Visual field examination revealed a superior altitudinal defect in the right eye and was normal in the left eye (Fig 2). Fluorescein angiography of the right eye revealed cilioretinal arteries that anastomosed to several retinal arteries at the disc and again peripheral to the disc (Fig. 3). The superior artery crossing the disc edge at the 12 o'clock position had three blood supplies, one from its main stem and two from separate cilioretinal arteries. The
angiogram revealed a lamellar pattern of flow on each side of the artery, as well as a central column of dye from the retinal artery. Three months later, the right optic disc became pale in the lower one-third, which corresponded to the dense scotoma present in the visual field of this eye. The vascular pattern of the fundus remained unchanged, although there were some capillary microaneurysms around one of the superotemporal veins of the right eye. Ophthalmodynamometry revealed retinal artery pressures of 30/26 mmHg in the right eye and 52/ 14 mmHg in the left eye. A repeat eye examination one year later showed no change. The following were normal: complete blood count, electrolytes, urinalysis, leukocyte differential count, sedimentation rate, serum protein electrophoresis, quantitative serum immunoglobulins, lgA, lgG, and IgE levels, serum complement, antinuclear antibody, anti-native DNA, rheumatoid factor, lupus erythematosus clot, serology test for syphilis, purified protein derivative of tuberculin, Ivy bleeding time, platelets, plasma clot retraction, platelet aggregation, prothrombin consumption, protamine gel test, fibrinogen, fibrin split products, chest roentgenogram, and electrocardiogram. The patient was treated with dipyridamole, 25 mg orally three times per day, and acetylsalicylic acid (Ascriptin), 10 grains orally three times a day, for 11 months, with slow but steady improvement of the skin lesions. She was in good health after a follow-up of 4 years.
Other cases of Degos' disease with ocular involvement. From 1960 to 1981, nine cases of Degas' disease
Fig 3. F1uorescein angiograms of right fundus showing cilioretinal arteries anastomosing with retinal arteries. Top left, choroidal phase. Top right, early arterial phase. Bottom left, mid-arterial phase. The superior retinal artery crossing the 12 o'clock disc edge has three blood supplies: one from its main stem and two from two separate cilioretinal arteries.
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were diagnosed at the Mayo Clinic, A more detailed clinicopathologic study of these cases is reported elsewhere. 5 In addition to the patient discussed here, three patients had signs or symptoms of ocular involvement. Two patients complained of"fuzzy vision," and on examination, both had nystagmus, right gaze paralysis, disconjugate eye movements, and dilated pupils that were poorly reactive to light. The third patient had bilateral papilledema. All three patients had involvement of the central nervous system with malignant atrophic papulosis, and we regard these ocular findings as secondary to changes in the central nervous system. No effective treatment was available for these patients.
DISCUSSION Malignant atrophic papulosis may involve multiple organ systems of the body. It has been stated that males are affected more often than females and that males have worse prognoses than females. 6 In our series, about half of the patients were males, and all of the fatalities occurred in males. In our series, there appears to be no age predilection. It is difficult to make a generalization on the age and sex distribution of this disease because of the rarity of its occurrence. The cutaneous eruption is the most characteristic symptom, but the very severe lesions occur in the gastrointestinal tract (especially the small intestine) and the nervous system. The skin lesions are quite specific and occur in bouts and are usually the first sign of the disease. Isolated, noncontiguous lesions pass through progressive stages from small, pinkish-grayish-yellow papules that later become umbilicated and centrally depressed. The lesions are not painful and usually are located on the trunk and upper body, sparing the head and peripheral extremities. Although they may be delayed for several years, the gastrointestinal manifestations are generally the most pronounced and tend to occur shortly after the skin lesions develop. 7-9 Vague abdominal discomfort, abdominal distention, and alternating diarrhea and constipation are the main features. Roentgenographic examination usually shows no abnormality, but at the time of surgical exploration, one can identify multiple "white infarcts" throughout the small intestine with an intact mucosa. The central or peripheral nervous system may be affected, usually after several bouts of the skin disease. 10•11 Multiple foci may be involved with vascular thrombosis, giving a wide array of neurologic signs, including meningoencephalitis, cranial nerve involvement, hemiparesis, and motor or sensory nerve abnormalities. Less frequently other organ systems can be involved, including the cardiovascular,9·12 pulmonary, 13·14 and genitourinary9·12 systems. Death can occur from gastrointestinal hemorrhage and perforation or from cerebral infarction and hemorrhage within a few years of the onset of the disease. Ocular involvement by malignant atrophic papulosis has been reported affecting the eyelids, 15 - 17 bulbar
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conjunctivae6·9·10•16- 19 (Fig 1, bottom left), retina, and choroid. 1·6·9·16·17·20·21 Also, ocular manifestations such as diplopia, 22 visual field defects, 14·23 ophthalmoplegia, 22·24 ptosis, 22·25 papilledema, 10 and optic atrophy22 may occur secondary to involvement of the central nervous system. This case illustrates an ocular manifestation of malignant atrophic papulosis which has not been previously described. Our patient probably had a bilateral congenital anomalous tortuous retinal vascular pattern with collateral filling of the arteries from the cilioretinal vessels. The presence of pronounced bilateral tortuosity and the unique filling of the vessels from several cilioretinal vessels support the congenital nature of these vessels. An alternative explanation is that of a progressive, arteriolar narrowing secondary to a disease process that incited a collateral response. She developed an afferent pupillary defect and an altitudinal field loss that was probably secondary to a vascular occlusion within a portion of the optic nerve. The infarct probably originated from occlusion of the inferior macular arteriole; an arterial aneurysm was found on the lower temporal part of the disc, and there was slight pallor of this part of the disc. The retinal veins were enlarged and slightly irregular, possibly due to venous stasis from the low blood pressure in the eye. It was interesting that the diastolic and systolic pressures were nearly the same in the right eye. A differential diagnosis of the skin lesions seen in Degos' syndrome should include systemic lupus erythematosus. The typical skin lesions of lupus erythematosus usually are seen as atrophic, hyperkeratotic, erythematous plaques without porcelain-white centers. Histopathologic study in systemic lupus erythematosus usually reveals atrophy of epidermis, hydropic degeneration of basal cells, and dense lymphocytic infiltration around the skin appendages and blood vessels. Therefore, the clinical and histologic features of classic systemic lupus erythematosus can be easily differentiated from those of Degos' syndrome. The cause and pathogenesis of the disease are still unknown. The common vascular lesion seen in all of the organ systems involved with this disorder is an obliterating arteriolitis or endovasculitis with secondary thrombosis and slow tissue necrosis. 10•21 Roenigk and Farmer 13 suggested that intravascular coagulation could be a factor in the pathogenesis of this disease. Black, Nishioka, and Levene 26 suggested that a disturbance of endothelial function leads to impairment of the normal fibrinolytic activity, causing a slow occlusion of arterioles. This is the rationale for the use of dipyridamole and acetylsalicylic acid in the case reported. Using electron microscopy, Howard and Nishida 16 found cytoplasmic inclusions within endothelial cells and suggested a possible viral cause. Results of various immunologic tests usually have been negative. 26 Soter et al27 suggested that the cutaneous lesions of malignant atrophic papulosis resulted from a lymphocytemediated necrotizing vasculitis that affects the entire cutaneous microvasculature. The dermatopathologic findings of the nine cases at the Mayo Clinic support this concept. 5
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OPHTHALMIC CHANGES OF DEGOS' DISEASE
REFERENCES 1. Kohlmeier W. Multiple Hautnekrosen bei Thrombangiitis obliterans. Arch Dermatol Syphil 1941; 181:783-92. 2. Degos R, Delort J, Tricot R. Dermatite papulo-squameuse atrophiante. Bull Soc Fr Dermatol Syphiligr 1942; 49:148-50. 3. Dubin HV, Stawiski MA. Systemic lupus erythematosus resembling malignant atrophic papulosis. Arch Intern Med 1974; 134:321-3. 4. Black MM, Hudson PM. Atrophia blanche lesions closely resembling malignant atrophic papulosis (Degos' disease) in systemic lupus erythematosus. Br J Dermatol 1976; 95:649-52. 5. Su WPD, Schroeter AL, Lee DA, et al. The clinical and pathologic spectrum of Degos' disease (malignant atrophic papulosis) (in preparation). 6. Henkind P, Clark WE II. Ocular pathology in malignant atrophic papulosis: Degos' disease. Am J Ophthalmol 1968; 65:164-9. 7. Degos R, Delort J, Tricot R. Papulose atrophiante maligne (syndrome cutaneo-intestinal mortel). Bull Mem Soc Moo Hop Paris 1948; 64:803-6. 8. Black MM, Jones EW. Malignant atrophic papulosis (Degos' syndrome). Br J Dermatol 1971; 85:290-2. 9. Strole WE Jr, Clark WH Jr, lsselbacher KJ. Progressive arterial occlusive disease (Kohlmeier-Degos): a frequently fatal cutaneosystemic disorder. N Engl J Med 1967; 276:195-201. 10. Winkelmann RK, Howard FM Jr, Perry HO, Miller RH. Malignant papulosis of skin and cerebrum; a syndrome of vascular thrombosis. Arch Dermatol 1963; 87:54-62. 11. Gever SG, Freeman RG, Knox JM. Degos' disease (papulosis atrophicans maligna): report of a case with degenerative disease of the central nervous system. South Med J 1962; 55:56-60. 12. Naylor D, Mullins JF, Gilmore JF. Papulosis atrophicans maligna (Degos's disease); report of the first United States case and review of the literature. Arch Dermatol 1960; 81:189-97. 13. Roenigk HH Jr, Farmer RG. Degos' disease (malignant papulosis); report of three cases with clues to etiology. JAMA 1968; 206: 1508-14. 14. Vanderhaeghen JJ, Joffroy A, Achten G, et al. Lesions vasculaires dans Ia papulose atrophiante maligne de Degos: atteinte disseminee
du systeme nerveux avec infiltration lipidique de l'intima des arteres sous-arachno'1aiennes. Pathol Eur 1968; 3:1-26. 15. Feuerman EJ. Papulosis atrophicans maligna Degos with microaneurysms of the conjunctiva. Arch Dermatol 1966; 94:440-5. 16. Howard RO, Nishida S. A case of Degos' disease with electron microscopic findings. Trans Am Acad Ophthalmol Otolaryngol1969; 73:1097-112. 17. Howard RO, Klaus SN, Savin RC, Fenton R. Malignant atrophic papulosis (Degos' syndrome). Arch Ophthalmol 1968; 79:262-71. 18. Ingram JT, Sutherland TW. Multiple skin necroses (arteriolar). Arch Dermatol 1957; 75:820-5. 19. Mawas J, Sidi E. Premiere localisation oculaire de Ia papulose atrophiante maligne. Bull Soc Ophtalmol Fr 1961; no. 2:70-4. 20. Craps L. Papulose atrophiante maligne (Degos). Arch Belg Dermatol Syphiligr 1959; 15:188-96. 21. Sidi E, Reinberg A, Spinasse JB, Hincky M. Lethal cutaneous and gastrointestinal arteriolar thrombosis (malignant atrophying papulosis of Degos). JAMA 1960; 174:1170-3. 22. Culicchia CF, Gol A, Erickson EE. Diffuse central nervous system involvement in papulosis atrophicans maligna. Neurology 1962; 12:503-9. 23. Kalis B, Guilaine R, Fenzy A, et al. A propos d'un nouveau cas de papulose maligne de Degos. Bull Soc Fr Dermatol Syphiligr 1968; 75:35-9. 24. Horner FA, Myers GJ, Stumpf DA, et al. Malignant atrophic papulosis (Kohlmeier-Degos disease) in childhood. Neurology 1976; 26: 317-21. 25. Howsden SM, Hodge SJ, Herndon JH, Freeman RG. Malignant atrophic papulosis of Degos; report of a patient who failed to respond to fibrinolytic therapy. Arch Dermatol 1976; 112:1582-8. 26. Black MM, Nishioka K, Levene GM. The role of dermal blood vessels in the pathogenesis of malignant atrophic papulosis (Degos' disease); a study of two cases using enzyme histochemical, fibrinolytic, electronmicroscopical and immunological techniques. Br J Dermatol 1973; 88:213-9. 27. Soter NA, Murphy GF, Mihm MC Jr. Lymphocytes and necrosis of the cutaneous microvasculature in malignant atrophic papulosis: a refined light microscope study. J Am Acad Dermatol 1982; 7:620-30.
299
Ophthalmic Changes of Degas' Disease (Malignant Atrophic Papulosis) DAVID A. LEE, MD,* W. P. DANIEL SU, MD,t THOMAS J. LIESEGANG, MD*
Abstract: A 49-year-old woman with typical skin lesions of Degas' disease was found to have an afferent pupillary defect, and altitudinal field loss. This loss was probably secondary to vascular occlusion in the optic nerve of a patient with a congenital anomalous retinal vascular pattern. The patient has had no other systemic involvement after a follow-up of 4 years. Three other patients seen in the past had eye involvement and involvement of the central nervous system and died between 1 and 16 years of the diagnosis. Multiple ocular manifestations of Degas' disease have been reported affecting the eyelids, bulbar conjunctivae, retina, and choroid in varying degrees. Diplopia, visual field defects, ophthalmoplegia, ptosis, papilledema, and optic atrophy are ocular changes secondary to involvement of the central nervous system. [Key words: conjunctival changes, Degas' disease, dermatologic changes, malignant atrophic papulosis, ocular changes, retinal changes.] Ophthalmology 91 :295-299, 1984
Degas' disease (malignant atrophic papulosis) is a rare disease of unknown cause which affects multiple organ systems in the human body. It was first described by Kohlmeier 1 in 1941 and further delineated by Degas et al 2 in 1942. It is characterized by an almost pathognomonic, asymptomatic, papular cutaneous eruption on the trunk and extremities that evolves to lesions, with atrophic porcelain-white centers surrounded by an erythematous telangiectatic border varying from 2 to 10 mm in diameter. Similar lesions have been described in patients with systemic lupus erythematosus. 3•4 Multiple ocular manifestations may occur with this disease. Recently, we saw a patient with optic nerve disease and an abnormal retinal vascular pattern that is probably related to this disease. We also reviewed the ocular features of other patients whom we have seen with Degas' disease.
From the Departments of Ophthalmology* and Dermatology,t Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Reprint requests to DA Lee, MD, cto Section of Publications, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
CASE REPORT A 49-year-old woman was seen at the Mayo Clinic in November 1977, complaining of asymptomatic, scattered, generalized, small pink papules with white centers. The skin lesions began to develop in 1970 and seemed to become more numerous with exposure to excessive sunlight, although the patient also noticed that new lesions developed without sun exposure. She complained of frequent feelings offainting, fatigue, palpitations, decreased exercise tolerance, anorexia, and loss of weight during the past year. She had noted pains in her neck, lower back, left hip, and left shoulder; numbness in her left hand; and decreased vision with a black spot in her right eye. Review of symptoms was positive for epigastric pain lasting 30 minutes to 2 hours after eating, but she had no nausea, vomiting, hematemesis, melena, or loose stools. Family history was noncontributory. On physical examination, the patient's vital signs were normal. Examination of the skin revealed discrete papular lesions 2 to 3 mm in diameter with porcelain-white depressed centers and erythematous borders (Fig l, top left). The skin lesions were in various stages of activity and were distributed over the upper and lower extremities, trunk, and the soles and dorsa of the feet. A skin biopsy specimen from the left buttock showed a wedge-shaped infarction of the upper dermis (Fig l, top right)
295
Fig 1. Top left, papules of Degos' disease, showing porcelain-white depressed centers and erythematous borders. Top right, skin biopsy specimen showing a wedge-shaped infarction in the upper dermis. (Hematoxylin and eosin X25.) Center left, fundus photograph showing right optic disc with vascular tortuosity and cilioretinal arteries which anastomose to retinal arteries at the disc and again peripheral to the disc. Note optic disc pallor inferotemporally. Center right, fundus photograph showing left optic disc with congenital tortuous vessels. Bottom left, typical telangiectatic conjunctival lesion seen in Degos' disease.
with lymphocytic infiltration perivascularly and fibrinoid necrosis of the blood vessel walls. No thrombosis was seen. A moderate deposit of mucin was present in the upper dermis, especially in the area of infarction. The clinical and histopathologic features of the skin lesions were considered to be diagnostic of Degos' disease. Direct immunofluorescence study of a skin specimen from the left thigh showed deposit of IgM in the superficial and deep blood vessels, consistent with vasculitis. Because of the patient's postprandial discomfort, upper gastrointestinal, stomach, esophagus, and duodenum roentgenographic studies were performed; all results were normal. Findings on a sigmoidoscopic examination to 17 em were normal, except
296
for mild internal and external hemorrhoids. Results of electromyography, sensory, and motor conduction studies of the left hand were normal. The ophthalmologic history was negative, except for a dark scotoma in the right eye, which had developed during the 6 months before examination at the Mayo Clinic. Visual acuity was 20/40 in the right eye and 20/25 in the left eye. The right eye had an afferent pupillary defect, and the left pupil was normal. Extraocular movements were full in both eyes. Slitlamp examination revealed no abnormality in either eye. Intraocular pressures were 14 mmHg in each eye. Fundus examination of each eye revealed marked tortuosity of both ar-
LEE, et al •
OPHTHALMIC CHANGES OF DEGOS' DISEASE
18
1000
20
Vos 2s
20
Voo 40
Fig 2. Visual field examination showing a superior altitudinal defect in right eye.
terioles and venules, particularly on the disc and in the area between the disc and the macula (Fig 1, center). Visual field examination revealed a superior altitudinal defect in the right eye and was normal in the left eye (Fig 2). Fluorescein angiography of the right eye revealed cilioretinal arteries that anastomosed to several retinal arteries at the disc and again peripheral to the disc (Fig. 3). The superior artery crossing the disc edge at the 12 o'clock position had three blood supplies, one from its main stem and two from separate cilioretinal arteries. The
angiogram revealed a lamellar pattern of flow on each side of the artery, as well as a central column of dye from the retinal artery. Three months later, the right optic disc became pale in the lower one-third, which corresponded to the dense scotoma present in the visual field of this eye. The vascular pattern of the fundus remained unchanged, although there were some capillary microaneurysms around one of the superotemporal veins of the right eye. Ophthalmodynamometry revealed retinal artery pressures of 30/26 mmHg in the right eye and 52/ 14 mmHg in the left eye. A repeat eye examination one year later showed no change. The following were normal: complete blood count, electrolytes, urinalysis, leukocyte differential count, sedimentation rate, serum protein electrophoresis, quantitative serum immunoglobulins, lgA, lgG, and IgE levels, serum complement, antinuclear antibody, anti-native DNA, rheumatoid factor, lupus erythematosus clot, serology test for syphilis, purified protein derivative of tuberculin, Ivy bleeding time, platelets, plasma clot retraction, platelet aggregation, prothrombin consumption, protamine gel test, fibrinogen, fibrin split products, chest roentgenogram, and electrocardiogram. The patient was treated with dipyridamole, 25 mg orally three times per day, and acetylsalicylic acid (Ascriptin), 10 grains orally three times a day, for 11 months, with slow but steady improvement of the skin lesions. She was in good health after a follow-up of 4 years.
Other cases of Degos' disease with ocular involvement. From 1960 to 1981, nine cases of Degas' disease
Fig 3. F1uorescein angiograms of right fundus showing cilioretinal arteries anastomosing with retinal arteries. Top left, choroidal phase. Top right, early arterial phase. Bottom left, mid-arterial phase. The superior retinal artery crossing the 12 o'clock disc edge has three blood supplies: one from its main stem and two from two separate cilioretinal arteries.
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were diagnosed at the Mayo Clinic, A more detailed clinicopathologic study of these cases is reported elsewhere. 5 In addition to the patient discussed here, three patients had signs or symptoms of ocular involvement. Two patients complained of"fuzzy vision," and on examination, both had nystagmus, right gaze paralysis, disconjugate eye movements, and dilated pupils that were poorly reactive to light. The third patient had bilateral papilledema. All three patients had involvement of the central nervous system with malignant atrophic papulosis, and we regard these ocular findings as secondary to changes in the central nervous system. No effective treatment was available for these patients.
DISCUSSION Malignant atrophic papulosis may involve multiple organ systems of the body. It has been stated that males are affected more often than females and that males have worse prognoses than females. 6 In our series, about half of the patients were males, and all of the fatalities occurred in males. In our series, there appears to be no age predilection. It is difficult to make a generalization on the age and sex distribution of this disease because of the rarity of its occurrence. The cutaneous eruption is the most characteristic symptom, but the very severe lesions occur in the gastrointestinal tract (especially the small intestine) and the nervous system. The skin lesions are quite specific and occur in bouts and are usually the first sign of the disease. Isolated, noncontiguous lesions pass through progressive stages from small, pinkish-grayish-yellow papules that later become umbilicated and centrally depressed. The lesions are not painful and usually are located on the trunk and upper body, sparing the head and peripheral extremities. Although they may be delayed for several years, the gastrointestinal manifestations are generally the most pronounced and tend to occur shortly after the skin lesions develop. 7-9 Vague abdominal discomfort, abdominal distention, and alternating diarrhea and constipation are the main features. Roentgenographic examination usually shows no abnormality, but at the time of surgical exploration, one can identify multiple "white infarcts" throughout the small intestine with an intact mucosa. The central or peripheral nervous system may be affected, usually after several bouts of the skin disease. 10•11 Multiple foci may be involved with vascular thrombosis, giving a wide array of neurologic signs, including meningoencephalitis, cranial nerve involvement, hemiparesis, and motor or sensory nerve abnormalities. Less frequently other organ systems can be involved, including the cardiovascular,9·12 pulmonary, 13·14 and genitourinary9·12 systems. Death can occur from gastrointestinal hemorrhage and perforation or from cerebral infarction and hemorrhage within a few years of the onset of the disease. Ocular involvement by malignant atrophic papulosis has been reported affecting the eyelids, 15 - 17 bulbar
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conjunctivae6·9·10•16- 19 (Fig 1, bottom left), retina, and choroid. 1·6·9·16·17·20·21 Also, ocular manifestations such as diplopia, 22 visual field defects, 14·23 ophthalmoplegia, 22·24 ptosis, 22·25 papilledema, 10 and optic atrophy22 may occur secondary to involvement of the central nervous system. This case illustrates an ocular manifestation of malignant atrophic papulosis which has not been previously described. Our patient probably had a bilateral congenital anomalous tortuous retinal vascular pattern with collateral filling of the arteries from the cilioretinal vessels. The presence of pronounced bilateral tortuosity and the unique filling of the vessels from several cilioretinal vessels support the congenital nature of these vessels. An alternative explanation is that of a progressive, arteriolar narrowing secondary to a disease process that incited a collateral response. She developed an afferent pupillary defect and an altitudinal field loss that was probably secondary to a vascular occlusion within a portion of the optic nerve. The infarct probably originated from occlusion of the inferior macular arteriole; an arterial aneurysm was found on the lower temporal part of the disc, and there was slight pallor of this part of the disc. The retinal veins were enlarged and slightly irregular, possibly due to venous stasis from the low blood pressure in the eye. It was interesting that the diastolic and systolic pressures were nearly the same in the right eye. A differential diagnosis of the skin lesions seen in Degos' syndrome should include systemic lupus erythematosus. The typical skin lesions of lupus erythematosus usually are seen as atrophic, hyperkeratotic, erythematous plaques without porcelain-white centers. Histopathologic study in systemic lupus erythematosus usually reveals atrophy of epidermis, hydropic degeneration of basal cells, and dense lymphocytic infiltration around the skin appendages and blood vessels. Therefore, the clinical and histologic features of classic systemic lupus erythematosus can be easily differentiated from those of Degos' syndrome. The cause and pathogenesis of the disease are still unknown. The common vascular lesion seen in all of the organ systems involved with this disorder is an obliterating arteriolitis or endovasculitis with secondary thrombosis and slow tissue necrosis. 10•21 Roenigk and Farmer 13 suggested that intravascular coagulation could be a factor in the pathogenesis of this disease. Black, Nishioka, and Levene 26 suggested that a disturbance of endothelial function leads to impairment of the normal fibrinolytic activity, causing a slow occlusion of arterioles. This is the rationale for the use of dipyridamole and acetylsalicylic acid in the case reported. Using electron microscopy, Howard and Nishida 16 found cytoplasmic inclusions within endothelial cells and suggested a possible viral cause. Results of various immunologic tests usually have been negative. 26 Soter et al27 suggested that the cutaneous lesions of malignant atrophic papulosis resulted from a lymphocytemediated necrotizing vasculitis that affects the entire cutaneous microvasculature. The dermatopathologic findings of the nine cases at the Mayo Clinic support this concept. 5
LEE, et al
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OPHTHALMIC CHANGES OF DEGOS' DISEASE
REFERENCES 1. Kohlmeier W. Multiple Hautnekrosen bei Thrombangiitis obliterans. Arch Dermatol Syphil 1941; 181:783-92. 2. Degos R, Delort J, Tricot R. Dermatite papulo-squameuse atrophiante. Bull Soc Fr Dermatol Syphiligr 1942; 49:148-50. 3. Dubin HV, Stawiski MA. Systemic lupus erythematosus resembling malignant atrophic papulosis. Arch Intern Med 1974; 134:321-3. 4. Black MM, Hudson PM. Atrophia blanche lesions closely resembling malignant atrophic papulosis (Degos' disease) in systemic lupus erythematosus. Br J Dermatol 1976; 95:649-52. 5. Su WPD, Schroeter AL, Lee DA, et al. The clinical and pathologic spectrum of Degos' disease (malignant atrophic papulosis) (in preparation). 6. Henkind P, Clark WE II. Ocular pathology in malignant atrophic papulosis: Degos' disease. Am J Ophthalmol 1968; 65:164-9. 7. Degos R, Delort J, Tricot R. Papulose atrophiante maligne (syndrome cutaneo-intestinal mortel). Bull Mem Soc Moo Hop Paris 1948; 64:803-6. 8. Black MM, Jones EW. Malignant atrophic papulosis (Degos' syndrome). Br J Dermatol 1971; 85:290-2. 9. Strole WE Jr, Clark WH Jr, lsselbacher KJ. Progressive arterial occlusive disease (Kohlmeier-Degos): a frequently fatal cutaneosystemic disorder. N Engl J Med 1967; 276:195-201. 10. Winkelmann RK, Howard FM Jr, Perry HO, Miller RH. Malignant papulosis of skin and cerebrum; a syndrome of vascular thrombosis. Arch Dermatol 1963; 87:54-62. 11. Gever SG, Freeman RG, Knox JM. Degos' disease (papulosis atrophicans maligna): report of a case with degenerative disease of the central nervous system. South Med J 1962; 55:56-60. 12. Naylor D, Mullins JF, Gilmore JF. Papulosis atrophicans maligna (Degos's disease); report of the first United States case and review of the literature. Arch Dermatol 1960; 81:189-97. 13. Roenigk HH Jr, Farmer RG. Degos' disease (malignant papulosis); report of three cases with clues to etiology. JAMA 1968; 206: 1508-14. 14. Vanderhaeghen JJ, Joffroy A, Achten G, et al. Lesions vasculaires dans Ia papulose atrophiante maligne de Degos: atteinte disseminee
du systeme nerveux avec infiltration lipidique de l'intima des arteres sous-arachno'1aiennes. Pathol Eur 1968; 3:1-26. 15. Feuerman EJ. Papulosis atrophicans maligna Degos with microaneurysms of the conjunctiva. Arch Dermatol 1966; 94:440-5. 16. Howard RO, Nishida S. A case of Degos' disease with electron microscopic findings. Trans Am Acad Ophthalmol Otolaryngol1969; 73:1097-112. 17. Howard RO, Klaus SN, Savin RC, Fenton R. Malignant atrophic papulosis (Degos' syndrome). Arch Ophthalmol 1968; 79:262-71. 18. Ingram JT, Sutherland TW. Multiple skin necroses (arteriolar). Arch Dermatol 1957; 75:820-5. 19. Mawas J, Sidi E. Premiere localisation oculaire de Ia papulose atrophiante maligne. Bull Soc Ophtalmol Fr 1961; no. 2:70-4. 20. Craps L. Papulose atrophiante maligne (Degos). Arch Belg Dermatol Syphiligr 1959; 15:188-96. 21. Sidi E, Reinberg A, Spinasse JB, Hincky M. Lethal cutaneous and gastrointestinal arteriolar thrombosis (malignant atrophying papulosis of Degos). JAMA 1960; 174:1170-3. 22. Culicchia CF, Gol A, Erickson EE. Diffuse central nervous system involvement in papulosis atrophicans maligna. Neurology 1962; 12:503-9. 23. Kalis B, Guilaine R, Fenzy A, et al. A propos d'un nouveau cas de papulose maligne de Degos. Bull Soc Fr Dermatol Syphiligr 1968; 75:35-9. 24. Horner FA, Myers GJ, Stumpf DA, et al. Malignant atrophic papulosis (Kohlmeier-Degos disease) in childhood. Neurology 1976; 26: 317-21. 25. Howsden SM, Hodge SJ, Herndon JH, Freeman RG. Malignant atrophic papulosis of Degos; report of a patient who failed to respond to fibrinolytic therapy. Arch Dermatol 1976; 112:1582-8. 26. Black MM, Nishioka K, Levene GM. The role of dermal blood vessels in the pathogenesis of malignant atrophic papulosis (Degos' disease); a study of two cases using enzyme histochemical, fibrinolytic, electronmicroscopical and immunological techniques. Br J Dermatol 1973; 88:213-9. 27. Soter NA, Murphy GF, Mihm MC Jr. Lymphocytes and necrosis of the cutaneous microvasculature in malignant atrophic papulosis: a refined light microscope study. J Am Acad Dermatol 1982; 7:620-30.
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