Lethal systemic degos disease with prominent cardio-pulmonary involvement.

A 48-year-old man presented with acute abdominal pain underwent laparotomy that revealed two perforated ulcers in jejunum. He had skin lesions with porcelain white atrophic scar which were ignored for 3 years, whereas the disease revealed own malignant nature and progressed to nervous, gastrointestinal, and cardiopulmonary systems. The diagnosis of Degos disease was established on the basis of clinical and histopathological features. He expired due to cardio-pulmonary insufficiency after 5 months from the onset of systemic involvement. Autopsy showed diffuse fibrotic changes in serosal membranes and internal organs. Distribution of skin lesions that involved palmoplantar surfaces, genitalia and scalp and, furthermore, course of disease as rapid progressive cardio-polmunary involvement are remarkable point in this patient. On the other hand, this case highlights importance of clinicopathologic correlation, specially in the dermatologic field.

Introduction

Degos disease (DD), also known as malignant atrophic papulosis or lethal cutaneous and gastrointestinal arteriolar thrombosis, is a rare occlusive arteriopathy with unknown pathogenesis that involves small caliber vessels of the dermis, gastrointestinal tract, central nervous system, and occasionally other organs. Kohlmeier described the disease for the first time at 1941. Next year, Degos presented DD as a distinct entity and coined its name.[12] We found approximately 150 reported cases in the literature. It is now well known that this disorder usually occurs in Caucasian young adults and is more common and sever in males than females. Although most cases are sporadic, familial variant with an autosomal dominant pattern were also described. More or less, the first manifestation of DD is skin rash and in about 15% of patients, disease remains limited to skin (benign form) whereas in others progresses to systemic involvement (malignant form). Until now no successful medical therapy is known.[3] We present a systemic DD with certainly malignant course.

Case Report

A 48-year-old Caucasian man presented to the emergency department with 5-day history of generalized abdominal pain, nausea, and vomiting which deteriorated and finally developed bloody diarrhea. He never had any previous history of gastrointestinal disorders. He also complained from progressive weakness and impaired sensation in the legs and urge incontinency from 1 month ago.

His medical history was notable for skin lesions persisting for over 3 years, first appeared as pink/reddish rash accompanied by a slight burning sensation then resolved within a few weeks leaving white depressed lesions. These lesions spread from the trunk to extremities. Familial history was unremarkable.

On physical examination he was ill, tachycardic, and feverish.

Skin examination revealed multiple erythematous papules (up to 100 papules, 2-10 mm in diameter) some with necrotic centers, distributed around the trunk, neck, scalp, extremities, genitalia and palmoplantar, sparing the face. The developed papules had a white color atrophic center that was surrounded by raised erythematous telangiectatic rim leaving depressed scar behind [Figure 1a and d]. Oral mucosa was not affected.

Figure 1

Typical skin lesions with atrophic porcelain white center surrounded by erythematous and telangiectatic rim on: (a) trunk, (b) genitalia, (c) palm, (d) sole

The abdomen was significantly tense with guarding and diffuse tenderness, which suggested surgical acute abdomen.

Neurologic examination showed spastic paraparesis with a sensory level at T4, which was suggestive for spinal lesion. Other examinations were unremarkable.

The patient underwent laparotomy. There was pus collection below the mesocolon on the left side of Treitz ligament. The jejunum contained two perforated ulcers (each one were 5 mm in diameter and 5 cm apart). Other parts of the gastro-intestinal tract were free of disease. A biopsy was taken from border of ulcers then repaired in two layers and peritoneal cavity irrigated with abundant fluid.

On the sixth day of admission patient experienced acute neurologic deficit as complete left hemiplegia including his face.

Laboratory investigations including CBC, routine chemistry, coagulation profile, VDRL, ANA, cANCA, pANCA, anti-dsDNA, LE cell, RF, antiphospholipid antibody, anticardiolipin antibody, CH50, HLA B5, HIV antibody, HCV antibody were negative or within normal reference ranges but HBS Ag was positive. PPD was negative. Erythrocyte sedimentation rate and C-reactive protein were slightly increased. Cerebrospinal fluid examination yield normal protein and cell count.

Pathologist reported that histopathological features in specimens from skin and jejunal lesions are similar and show dense dermal fibrosis and submucosal collagen deposition, respectively. He suggested scleroderma as possible diagnosis but clinical finding was not compatible.

Brain MRI revealed small vessel disease in both cerebral hemispheres with the ischemic process in right side of pons without abnormal tissue enhancement. Although examination revealed spinal involvement the spinal MRI was normal [Figure 2]. Thoracic CT scan demonstrated bilateral mild pleural effusion.

Figure 2

T1-weighted Brain MRI from patient showing infarction in right side of pons

Although paraclinic did not support specific diagnosis, due to strong clinical suspicion to vasculitis and serious patient condition, we added prednisolone to his medications (antibiotics with enteropathogenic coverage).

Patient's problems persisted and 4 days later, another complaint submerged, manifesting with nausea and vomiting, oral intolerance, accompanied by wound dehiscence, and excess leakage of yellow/orange fluid from incision site. Investigation revealed simple small bowel enterocutaneous fistula. Oral feeding was stopped and octreotide administered. In addition, he developed atrial fibrillation arrhythmias which subsequently controlled by amiodarone.

Attempting to make a definitive diagnosis, we requested dermatologic consultation. Dermatologist noted cutaneous “porcelain white atrophic scar” with erythematous and telangiectatic rim, strong characteristic of DD. A elliptical skin biopsy showed epidermal atrophy, ulceration with overlying hyperkeratosis, and underlying wedge shape ischemic area with uniformly acellular hypereosinophilic dermis. There was mild perivascular lymphocytic infiltration at the edge of ischemic wedge. Endothelial swelling and obliteration of lumen and fibrin deposition around vessels were also identified [Figures 3a–b]. The review of the peritoneal biopsy showed multifocal PMN infiltration and necrosis as well as small vessel thrombosis.

Figure 3

Histopathological features of an established lesion (hematoxylin and eosin). (a) Low-power view showing atrophy, ulceration and hyperkeratosis in epidermis, besides a wedge-shape ischemic area with fibrosis in dermis. (b) High-power view showing perivascular lymphocytic infiltration with endothelial swelling

On the basis of clinical and histopathological features the diagnosis of DD with multisystemic involvement was made.

Thereafter, octreotide and antibiotics were continued, prednisolone was stopped, pentoxifylline in combination with antiplatelet and anticoagulant therapy beside total parenteral nutrition was initiated. Further laboratory tests revealed normal levels of proteins C and S, antithrombin3 and hemocystein. Tests for factor 5 Leiden was also negative.

During the follow up, since no new skin lesions appeared and discharge of fistula limited, he developed progressive dyspnea with multiple episodes of respiratory distress. Repeated chest radiograph showed worsening of effusion. During 5-month period, patient's condition exacerbated and accompanied with generalized edema, alternation of consciousness and hemodynamic instability requiring mechanical ventilation and also administration of inotropic and vasopressor agents. Ultimately, he expired due to cardio-pulmonary failure. The autopsy performed. The pleura showed severe fibrotic thickening, hemorrhagic fibrinoid exudate with adhesions to the chest wall and compression collapse of both lungs specially in right. Despite severe pericardial fibrosis, heart was slack and large. In abdomen, peritoneal fibrosis, ascites, and adhesions were present along the gastrointestinal tract. The bowel contained hemorrhagic fluid. In addition, numerous erosions, ulcers, and necrotic areas with perforation in the bowel presented. The liver was strictly fibrotic. Also, with less severity, there was similar pattern in kidneys and vesicle. The cause of death was DD-induced severe restrictive cardio-pulmonary insufficiency.

Discussion

DD is a rare disorder characterized by multiple infarctive lesions in the skin and internal organs. Thrombotic occlusion of small- and medium-size vessels ultimately leads to clinical manifestations. Until now the precise etiology of the thrombosis is not elucidated; however different theories exist, describing DD as coagulopathy, vasculitis, or primary disorder of endothelial cells.[4] Caviness et al. proposed the hypothesis that a dysregulation of vascular remodeling and increased vascular permeability due to increased VEGF production, as well as a prothrombotic process occurs in DD.[5] Besides, DD has an inconspicuous clinical course. In some patients disease is limited to skin for many years (benign form), in contrast, in most cases it has an unfavorable course and progresses to systemic involvement (malignant form). Until now it is impossible to predict precise prognosis.[4-9]

Some authors suggested that Degos is not a distinct disease and proposed it as a morphologic pattern or a variant of lupus erythematosus.[410] However, there are strong evidences against this theory (lack of photosensitivity and facial lesions, unresponsiveness to corticosteroids and immunomodulatory agents, invariable fatal course in systemic form, and negative DIF findings in DD).[3]

Mostly, the first manifestation of DD is skin lesions which can develop at any site; however the face, palms, soles, genitalia, and scalp tend to be spared.[3-5] Morphology and less importantly distribution of skin lesions provide keys for early diagnosis. Systemic manifestations usually develop during weeks to years following the onset of skin lesions or even rarely precede the skin lesions.[11] Gastrointestinal tract, predominantly small bowel, is involved in about 50-60% of the patients with clinical manifestations ranging from dyspepsia to perforation of viscous and peritonitis (the most catastrophic event in DD).[12-15] Neurologic manifestations occur in about 20% of the patients, which vary according to site of involvement. Ocular involvement is present in 13% of patients.[15] Involvement of other organs such as oral cavity, pleura, pericardium, lung, heart, kidney, bladder, and pancreas are usually minor manifestations of the disease without clinical significance.[4]

There is no specific laboratory test for diagnosis of DD. The characteristic histological features are wedge-shaped tissue necrosis and thrombosis of the supplying blood vessels but not evident in all cases.[3]

Varieties of therapeutic modalities such as antithrombotic, anti-inflammatory, and immunomodulatory agents have been suggested but are not proven to be effective.[16]

The outcome of DD is usually fatal (50-60%) within 2-3 years (range 5 months to 14 years) from the onset of systemic involvement. Death most often occurs due to intestinal perforation, peritonitis and sepsis (61%), CNS bleeding (18%), and pleural/pericardial involvement (16%).[1415]

The physicians, especially surgeons, gastroenterologists and neurologists, should consider DD as a rare cause of common complaints of patients. Typical skin lesions should remind them of this disease. Although central porcelain white scar rimmed by erythema and telangiectasia is pathognomonic of DD, but this lesion is not familiar for most physicians. On the basis of this report and multiple similar reports,[81117-19] involvement of soles, palms, and genitalia is not rare in DD. On the other hand, pleural and pericardial involvements have been usually reported as incidental findings at autopsy or minor manifestations of prolonged disease. Pierce et al. and Mauad et al. described three cases with pleural and pericardial involvements as important clinical manifestations of DD.[2021] Their patients had relatively prolonged survival (5, 6, and 11 years), whereas in our patient, ran as rapid progressive course. Besides, there are evidences such as present patient regarding the use of immunomodulatory agents and systemic corticosteroids exacerbate gastrointestinal manifestations; therefore physicians should distinguish DD from vasculitis as close mimicker.[1116] Furthermore, post-mortem examination revealed diffuse fibrotic changes in DD. We think that anti-inflammatory agents specially aspirin delay this inevitable process, however further studies necessitate. Ultimately, correct diagnosis of diseases, specially in the dermatologic field, requires close clinicopathologic correlation. Indeed, we need a dermatopathologist who receive complete clinical description of patient from clinician; also clinician should consider microscopic description and not only end suggestion.