Degos Disease 

Updated: Feb 07, 2017
Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD 

Overview

Background

In 1941, in an article entitled "Multiple Hautrekrosen bei Thromboangiitis obliterans," Kohlmeier described a case of a disease that has now been termed malignant atrophic papulosis (MAP) or Degos disease (DD). Degos recognized it as a distinct clinical entity in 1942.

Research suggests that Degos disease is a genetic disease of complement or some other clotting factor or system.[1] This is supported by the fact that eculizumab, a C5 blocker, can effectively treat systemic Degos disease.

Broadly speaking, Degos disease is a vasculopathy or an endovasculitis. It is an occlusive arteriopathy involving small-caliber vessels. Specifically, it is a progressive, small- and medium-size arterial occluding disease, leading to tissue infarction and initially involving the skin. Degos disease occurs both in a limited benign, cutaneous form and in a potentially lethal multiorgan, systemic variant.[2]

In the skin, Degos disease initially manifests with erythematous, pink or red papules. These papules heal to leave scars with pathognomonic, central, porcelain white atrophic centers. These papules usually have a peripheral telangiectatic rim.

In the systemic variant of Degos disease, the gastrointestinal tract is affected in 50% of cases. Intestinal perforation is the most severe complication and the most common cause of death in systemic Degos disease.[3] Other systems can also be involved; approximately 20% of cases of systemic Degos disease involve the CNS. Systemic manifestations usually develop from weeks to years after the onset of skin lesions, or, in rare instances, they may precede the skin lesions.

Because of the broad overlap in clinical and histological findings, High et al[4] contended in 2004 that Degos disease may not be a specific entity but, rather, may represent a common end point to a variety of vascular insults, many of which have not been fully elucidated. In 2003, Ball et al[5] proposed that Degos disease is just a variant of lupus.

Unlike lupus, (1) Degos disease does not involve the face, (2) it does not respond to therapies such as corticosteroids that at least abate lupus, (3) it does not manifest with photosensitivity, (4) viral inclusions are present in some cells in patients with Degos disease, and (5) systemic Degos disease is universally fatal, usually within 1-2 years, whereas lupus (even if severe) takes years to be fatal.[6]

Wilson et al[7] reiterated that malignant atrophic papulosis/Degos disease has both a (1) limited, cutaneous type and a (2) systemic, fatal variant.

Guhl has noted a case of Wegener granulomatosis that manifested with multiple whitish papules, perhaps similar to those in Degos disease.[8]

New cases of Degos disease continue to be described, with no fully effective cure yet devised.[9, 10]

Pathophysiology

The etiology and the pathophysiology of Degos disease are unknown. Some have classified Degos disease as a vasculitis, a mucinosis, or a thrombotic disorder. In most cases, no circulating immune complexes, antiendothelial cell antibodies, or anticardiolipin antibodies are isolated. Although, in some cases, antiphospholipid antibodies of uncertain significance are identified. A source of confusion exists in understanding atrophic papulosis. It is likely that the differences in blood vessels in each area of the body (eg, skin, brain, intestines) help explain the different phenotypes of disease.

Some authorities suggest that Degos disease involves a primary endothelial cell defect with secondary thrombosis, leading to infarctive changes. No evidence exists supporting specific antibody-mediated damage. Additionally, medications and toxic chemicals do not appear to induce Degos disease.

The actual physical damage to blood vessels involves, at least in part, impaired fibrinolytic activity and alterations in platelet function. Classifying Degos disease as a vasculitis may not be appropriate because inflammation of the vessel walls is minimal and because immune complexes have not been found in the vessel walls.

Three possible mechanisms for this pathology have been suggested: disturbance in immunity, viral infection, and abnormality in the clotting system of blood.

In familial cases, an autosomal dominant mode of inheritance has been suggested, but this is uncertain.

In molecular analysis of cases of Degos disease with only cutaneous lesions, no paramyxovirus was identified by polymerase chain reaction.

The effectiveness of eculizumab at treating Degos disease must transform our understanding of the disease. As eculizumab is a hematological drug that blocks complement component 5 (C5), Degos disease may, in fact, be a hematological/endothelial/clotting disease that involves C5 in some pathological cascade. Degos disease thus is not a disease of immunity and should not be considered as a vasculitis. A genetic defect that parallels that of paroxysmal nocturnal hemoglobinuria (PNH) would not be surprising. Scheinfeld has discussed this concept at length.[11]

Support for the idea that Degos disease is an genetic defect of the endothelial tissue (with or with out a viral trigger) comes from Passarini who noted that in a patient suffering from systemic Degos disease who received an organ transplant, who died, on autopsy did not have any Degos disease–like changes in the transplanted tissue.[12]

A report from Japan published in 2013 investigated the expression of stromal cell–derived factor (SDF)-1/CXCL12 in Degos disease. Bone marrow stromal and endothelial cells secrete SDF-1/CXCL12. SDF-1/CXCL12 activates megakaryocyte precursors. SDF-1/CXCL12 co-stimulates platelet activation. The study compared 2 patients with Degos disease, 1 patient with cryoglobulinemia, 1 patient with antiphospholipid syndrome, and 2 healthy controls. No staining was noted in the antiphospholipid syndrome, cryoglobulinemia, or control subjects. In the Degos disease patients, investigators saw intense SDF-1/CXCL12 staining infiltrating inflammatory cells. These cells were located in the perivascular, intravascular, and perineural tissue. This finding supports the theory that Degos disease is perhaps, in part, an endothelial disease.[13]

Epidemiology

Frequency

Degos disease is rare. About 200 cases have been reported in the world literature.

Race

Some state that Degos disease generally occurs in white young adults. However, Degos disease is reported in blacks in Africa, Arabs in Jordan,[14] Asians in Japan, and elsewhere. Any racial link is uncertain.

Sex

In 1997, Katz et al[15] noted that the disorder usually occurs in young adults, and the male-to-female ratio is approximately 3:1.

Wilson et al[7] reviewed benign cutaneous malignant atrophic papulosis in 34 men and women (30 adults and 4 kids) and noted that benign malignant atrophic papulosis is more commonly reported in women, at a female-to-male ratio of 3:1.

Age

All ages are affected. The fatal systemic variant of Degos disease can occur in children. In 1999, Lankisch et al[16] described a 16-year-old white adolescent girl with acute abdominal pain due to visceral involvement of Degos disease that required extensive small-bowel resection. The skin manifestations had been present for 2 years before the correct diagnosis was made. She died as a result of CNS involvement from Degos disease.

Jalil et al[17] described a case in a 2-year-old child who presented with chronic abdominal pain of uncertain origin.

The benign cutaneous variant of Degos disease can occur in adults. Wilson et al[7] looked at 34 patients with benign cutaneous malignant atrophic papulosis and found their average age was 37.6 years. In 1998, Farrell et al[18] described a case of a 44-year-old woman with Degos disease and a lupus anticoagulant who, 4 years later, was alive and without systemic involvement. Electron microscopy of the white papules demonstrated interwoven tubular structures within the endothelial cells. This was consonant with reports in previous studies of Degos disease. Farrell et al[18] thought that aspirin (300 mg/d) kept her cutaneous Degos disease in check. In 1998, Requena et al[19] described a 58-year-old homosexual man with AIDS who developed typical cutaneous lesions of malignant atrophic papulosis, with no visceral involvement detected 2 years after the diagnosis of Degos disease.

Degos disease can occur in infants. Degos disease has been reported in a 7-month-old girl who showed spontaneous aggregation of platelets. A good clinical response in this patient was obtained by treatment with aspirin and dipyridamole.[20]

Prognosis

Patients with only skin lesions may have a good prognosis. Gastrointestinal involvement may occur in as many as 60% of patients, and death in such cases is likely. About 15% of patients with Degos disease have long-term survival, with disease often limited to the skin and with no manifestations of fatal bowel or CNS involvement.

Systemic Degos disease is frequently fatal within 2-3 years from the onset of systemic involvement. The cause of death is usually intestinal perforation. However, the range of survival time from time of diagnosis varies from less than 1 year to more than 12 years. Other causes of death include bowel infarction, pleuropericardial pathology,[21] and neurologic infarction and hemorrhage.

Wilson et al[7] reviewed the 24 reported instances of malignant atrophic papulosis malignant/systemic type and benign/purely cutaneous type in pediatric patients. They found that 14 cases (58%) were fatal. Patients died an average of 3.6 years after the diagnosis of malignant atrophic papulosis.

In  one patient, in whom skin and abdominal symptoms occurred at the same time, death from bowel hemorrhage followed in 6 months.

In 1996, Subbiah et al[22] described the neurologic features of a series of 15 patients with Degos disease at the Mayo Clinic. Each patient had the white papules that are the hallmark of Degos disease (biopsy proven). Long-term follow-up revealed 6 patients were dead. Nine patients with skin lesions only were nearly asymptomatic. Immunosuppressive and antiplatelet agents did not halt disease progression. CNS infarcts and hemorrhages with intravascular thrombi and without evidence of vasculitis were notable findings at autopsy.

Notash et al[23] reported a 48-year-old Iranian man with lethal systemic Degos disease.

Two reports describe acute abdomen associated with Degos disease, one fatal.[24, 25]

When associated with gastrointestinal tract or central nervous system involvement, patients with Degos disease have a poor prognosis and a high mortality.

In patients with benign cutaneous Degos disease, immunosuppression (in 1 patient with cyclosporine) can cause Degos disease to evolve into systemic fatal disease.

Patient Education

Because systemic Degos disease is fatal, patients and their families should be educated in this regard.

 

Presentation

History

In most cases, the first manifestation of Degos disease is an eruption. A single center study of 39 patients with atrophic papulosis was performed by Theodoridis et al.[26] The manifestation of a cutaneous eruption always defined the onset of disease. The mean age of onset appeared to be 35.4 ± 12.3 years. The female-to-male ratio was 1.4:1. Familial occurrence was noted in 9% of cases. This study noted systemic signs in 29% of patients, appearing at 1 year (0.03-0.97 quantiles: 0-7 y). Theodoridis determined that the cohorts' prognosis was primarily determined by the existence of systemic involvement. Of patients with systemic manifestations, 73% developed intestinal perforation and died. None of the patients with only skin disease died. The cumulative 5-year survival rate in patients with systemic disease was reported at 54.5%.

Some have stated that the disease involves the skin as the sole clinical manifestation in 37% of patients. The gastrointestinal tract is involved in about 50% of patients.

Patients may have a family history of Degos disease. In 1997, Katz et al[15] described a familial variant of Degos disease.

Degos disease associated with a spontaneous cure of diabetes has been reported.[27]

Patients with Degos disease may have a history of a variety of abdominal complaints, manifesting with abdominal pain, abdominal distention, cramps, nausea, vomiting, diarrhea, or constipation. Sometimes, patients may state that they experience weakness, fatigue, or weight loss, or symptoms of malabsorption.

Degos disease has been associated with systemic diseases. Degos disease has occurred in patients with rheumatoid arthritis, HIV infection, and antiphospholipid antibodies and antiphospholipid syndrome.[28]

Patients may have a history of a variety of neurologic complaints that include facial and acral paresthesia, headaches, dizziness, seizures, hemiplegia, aphasia, paraplegia, and gaze palsy.

Patients may have a variety of eye problems, including diplopia, ptosis, and visual-field defects.

Patients may experience weakness, shortness of breath, and chest pain.

Inflammatory linear vasculopathy mimicking Degos disease has been described. This is important to note because Degos disease mimicking vasculitis has been described.

Saglik et al[29] noted a case of malignant atrophic papulosis with endocardial involvement and positive anticardiolipin antibodies.

A case of Degos disease occurring with diabetes mellitus, with biopsy findings of both Degos disease and hyaline diabetic microangiopathy, has been reported.[30]

Parvovirus B19–associated catastrophic endothelialitis with a Degos-like presentation has been noted.[31]

The benign variant developing during pregnancy has been described.[32]

Poststreptococcal vasculopathy that evolved into Degos disease–like white papules has been reported.[33]

Ortiz et al reported a case of cutaneous Degos disease that showed features of connective-tissue disease; a specific connective-tissue disease never developed in the patient.[34]

Physical Examination

The main physical finding of Degos disease is a skin rash that manifests with porcelain white scars. Degos disease also affects the eyes, the intestines, the brain, and other organs with a variety of physical findings.

The most visible manifestation of Degos disease is in the skin.

Degos disease manifests with (in most cases) multiple, small, red, raised papules that are 2-5 mm in diameter. After a few days, they enlarge and develop a central white spot that is depressed in comparison to the red skin around it, as shown in the images below. They heal, leaving depressed porcelain white scars with a rim of telangiectases. Note the images below.

Four papules of Degos disease located on upper-inn Four papules of Degos disease located on upper-inner arm in different stages of evolution. Courtesy of David F. Butler, MD.
Papule of Degos disease with central sclerosis and Papule of Degos disease with central sclerosis and telangiectasia. Courtesy of David F. Butler, MD.

The papules predominantly occur on the trunk and the arms. Degos papules commonly manifest on the penis.[23]

Degos more rarely occurs on the palms and soles.[23]  One case has noted that Degos occurred on the scalp. No cases known to the author note Degos disease-type papules on the face.

In a 17-month-old child, progressive involvement of the fingers and the toes with torpid ulcers and apical necrotic amputations has been reported.

Peristomal lesions have been reported.

The rash of Degos disease develops slowly and is usually mostly asymptomatic, but it may be accompanied by a slight burning sensation. The rash can arise anywhere except on the soles, the palms, and the face. The rash starts as pink or red papules that are 2-15 mm in diameter. The papules evolve into atrophic scars that are porcelain white. Sometimes, abdominal symptoms precede the rash, but this finding is uncommon.[35]

A variety of ocular findings occur in Degos disease. Posterior subcapsular cataracts,[36] visual field defects, ptosis, third cranial nerve palsies, blepharoptosis, and optic atrophy may be associated with Degos disease. Optical neuritis, papilledema, and scleral plaques can be present.[37] In 1986, Sibillat et al[38] reported that ophthalmologic symptoms were present in 35 of 105 extant reports of Degos disease. Degos disease manifested in the eye tissues, usually in the conjunctiva. The sclera, the episclera, the retina, the choroid, the optic nerve, and/or the neuro-ophthalmologic apparatus demonstrated damage consonant with Degos disease.

Constrictive pericarditis has been reported in Degos disease. This condition might be induced by pericardial vasculitis, thereby causing the left ventricular wall motion abnormality.

The lungs can be affected in Degos disease. Pulmonary manifestations include pleuritis and bilateral pleural effusions.

The liver and the kidneys may be involved and associated with a vasculitis.

The brain and the nerves can be affected in Degos disease. In 1 patient with Degos disease, the neurologic examination revealed a right-hemianopsia, paraparesis (with a sensory level at Th12), and a neurogenic bladder. In another patient, an ascending thoracic myelopathy was present. In 1996, at the Mayo Clinic, Subbiah et al[22] described a series of 15 patients. Ten patients developed neurologic manifestations. These findings included fatal hemorrhagic or ischemic strokes in 5, disabling polyradiculoneuropathy in 1, and nonspecific neurologic symptoms without objective findings in 4. Other manifestations include strokes, headaches, epilepsy, or nonspecific neurologic symptoms (eg, memory loss, altered sensation).

Patients experience abdominal pain. Gastrointestinal bleeding can result in vomiting blood or passing blood with bowel movements. Patients with Degos disease may have enterocutaneous fistulae.

Causes

The cause of Degos disease is unknown. Suggested causes include a virus, an immune defect, or a clotting defect.

Complications

Complications of Degos disease include the following:

  • Gastrointestinal bleeding and perforation

  • Neurologic bleeding and collapse

  • Cardiac pathologic conditions

  • Pulmonary pathologic conditions

  • Ocular complications

 

DDx

Diagnostic Considerations

Skin popping (intravenous and cutaneous microvascular drug abuse) with opiates has been reported to mimic malignant atrophic papulosis (Degos disease) with multiorgan involvement.[39]

Differential Diagnoses

 

Workup

Laboratory Studies

No specific laboratory test can be used to aid in diagnosing Degos disease (DD). In fact, most laboratory test results are normal, with the exception of the manifestation of anemia secondary to intestinal bleeding.

In 1 patient, laboratory examinations disclosed persistent elevations of the thrombin-antithrombin III complex, plasmin-alpha 2 plasmin inhibitor complex, and cytotoxic T-cell subset (CD8+ CD11-), illustrating the coagulative, fibrinolytic, and immunologic implications of Degos disease.

In a series of 3 patients with Degos disease, prolonged euglobulin lysis time, increased plasminogen activator levels, and increased plasminogen activator inhibitor activities were detected before and after a venous occlusion test, indicating an inhibition of fibrinolysis.

In a series of 3 patients with Degos disease, electron microscopy demonstrated an increased number of Weibel-Palade bodies and a raised staining of von Willebrand factor in endothelial cells in 1 patient.

In a series of 3 patients, test results for coagulation and circulating anticoagulant were in the reference range.

In a series of 3 patients, the results of platelet adhesion showed decreased adhesion in 1 patient and increased adhesion in another patient. Platelet aggregation study results decreased to the reference range in 2 patients. In one patient, tests showed hyperactive spontaneous and induced platelet aggregation.

Amounts of protein in the cerebrospinal fluid and amounts of platelet aggregation have been reported as sharply increased in progressive stages of the disease. For example, laboratory results showed a gradual increase of cerebrospinal fluid proteins (from 156 mg/dL to 602 mg/dL) and an extremely increased amount of platelet aggregation.

In Degos disease, viruslike inclusions are frequently present in the endothelial cells and fibroblasts. C3 deposits and the presence of intracytoplasmic cylinders are also frequently present in the histiocytes.

Hohwy et al[40] reported a fatal case of systemic malignant atrophic papulosis (MAP) in a man with factor V Leiden mutation and lupus anticoagulant.

Imaging Studies

MRI of the brain can show multiple cerebral infarctions accompanied by small hemorrhagic areas and gadolinium-diethylenetriamine pentaacetic acid enhancement of the dura.[41] They can also reveal intracerebral bleeding, subdural hemorrhage, and cord infarcts.

A cerebral angiogram may reveal narrowing and occlusion of small intracranial arteries. Specifically, a cerebral angiogram can depict stenosis, ectasia, and aneurysms involving the peripheral branch of arteries.[41]

EEG tests have shown generalized nonspecific slowing.

In some patients, electromyograms demonstrate axonal and demyelinating polyneuropathy.

With angiograms, stenoses can be observed in the celiac artery and the small arteries in the kidney.

In some patients, chest radiographs have depicted extensive calcification of the pericardium. Although pleural involvement and pericardial involvement have been reported in Degos disease, constrictive pericarditis is most unusual, and radiographically demonstrable calcification of the pericardium has not been previously reported.

Matsuura et al[37] noted a fatal case of malignant atrophic papulosis involving the optic nerve and spinal cord. MRI of the optic nerve demonstrated (1) pathologic signal enhancement on fat-suppressed, T1-weighted images after intravenous meglumine gadopentetate infusion and (2) a sawtooth pattern over 7 vertebral segments of the spinal cord on T2-weighted sagittal images. These findings were confirmed at autopsy, during which pathologists grossly noted (1) a pronounced decrease of myelinated nerve fibers in the left optic nerve with thrombotic obstruction of the central retinal artery, (2) spongy degeneration in all levels of the spinal cord, and (3) patchy and moth-eaten patterns due to thromboses and endothelial proliferation in subarachnoid vessels.

Amaravadi et al[42] described CT scan findings a 40-year-old woman. CT scanning of the abdomen and pelvis with oral and intravenous contrast demonstrated extensive ascites and nodular thickening of the omentum. A subsequent CT scan of the abdomen and pelvis with intravenous contrast showed a large amount of ascites with small bowel wall thickening and patchy mucosal perfusion and intraluminal hemorrhage into a loop of infarcted jejunum, which was later confirmed at autopsy to be an intraluminal clot. A final CT scan of the abdomen and pelvis with only intravenous contrast, which was performed to investigate worsening peritonitis, showed extensive pathology. An axial image demonstrated pneumoperitoneum with edematous and hyperemic small bowel loops consistent with small bowel ischemia. Discontinuity in the wall of a loop of jejunum was consistent with perforation. Multiple jejunal perforations were later demonstrated at autopsy.

Other Tests

Endoscopy of the gastrointestinal tract (ie, stomach, esophagus, duodenum, colon, rectum) can show infarcted lesions or ulcers.

Laparoscopy of the intestine can show similar type lesions that manifest with white plaques with red borders on the serosal surface of the bowel and the peritoneum.

Laparoscopy demonstrates superiority over endoscopy at detecting GI involvement.[43]

In 2007, Amaravadi et al[42] reported autopsy findings from a 40-year-old female Degos disease patient. They found omental infarction and multiple yellow plaques on the serosal surface of the small bowel during an exploratory laparotomy.

Histologic Findings

Early papules in Degos disease are skin colored and can demonstrate a superficial and deep perivascular, periadnexal, and perineural chronic inflammatory cell infiltrate associated with interstitial mucin deposition, as shown in the images below.

Superficial and mid-dermal perivascular lymphocyti Superficial and mid-dermal perivascular lymphocytic infiltrate with focal vacuolar change at the dermoepidermal junction (hematoxylin and eosin, X100). Courtesy of David F. Butler, MD.
Alcian blue stain for mucin (X100). Courtesy of Da Alcian blue stain for mucin (X100). Courtesy of David F. Butler, MD.

A mild vacuolar interface reaction has been described. The vacuolar interface dermatitis, dermal mucin, and perivascular lymphoid infiltrate mimic lupus erythematosus.

Fully developed papules can be raised, with umbilicated porcelain-white centers and a surrounding erythematous rim. Histologically, these papules demonstrate wedge-shaped degeneration of collagen, as shown in the image below.

Wedge-shaped area of dermal sclerosis (hematoxylin Wedge-shaped area of dermal sclerosis (hematoxylin and eosin, X100). Courtesy of David F. Butler, MD.

An interface dermatitis can be present but is often limited to the central portion of the tissue examined histologically. Additionally, squamatization of the dermoepidermal junction, melanin incontinence, and epidermal atrophy can manifest.[44]

In many cases, an area of papillary dermal sclerosis manifests that mirrors the early stages of lichen sclerosus et atrophicus.

Hyperkeratosis, epidermal atrophy, dermoepidermal separation, edema, and papillary dermal necrosis occur. Fibrinoid necrosis and thrombosis occur in the papillary dermis and in the capillary and venules. Others have noted that skin biopsy specimens show hyperkeratosis, atrophy of the epidermis, and necrobiosis of the collagen layer. Well-developed papules of Degos disease with epidermal atrophy and hyperkeratosis overlying a wedge-shaped area of cutaneous ischemia extending into the deep dermis have also been observed.

A superficial and deep perivascular lymphocytic infiltrate can gather at the fringe of ischemic areas. Marked endothelial swelling and occasional platelet-fibrin thrombi are often noted. Infarctive changes or scattered necrotic keratinocytes may be present in the epidermis. Abundant acid mucopolysaccharides often occur in the dermis, mimicking dermal mucinosis.

Direct immunofluorescence examination does not yield definitive results. Perivascular fibrin and complement can be present. In one reported case, autopsy results demonstrated the clinical diagnosis of Degos disease based on the finding of thromboangiitis of the Burger type, with bland infarcts of the small intestine and perforation of the jejunum.

Microaneurysms of the bulbar conjunctival vessels have been described.

Changes in the kidneys manifest with thickening of the afferent glomerular arterioles and the capillary basement membrane.

In 2008, Notash et al[23] described a fatal case of Degos disease in a 48-year-old man whose autopsy findings demonstrated diffuse fibrotic changes in the serosal membranes and the internal organs.

 

Treatment

Medical Care

Until 2010, no medical therapy for Degos disease (DD) was noted to be uniformly effective. Antiplatelet drugs (eg, aspirin, dipyridamole) may reduce the number of new lesions in some patients with only skin involvement. Some believe intravenous immunoglobulin may have a role in treatment.[45] This has changed with the reports that eculizumab can effectively treat systemic Degos disease.[1]

The initial enthusiasm for eculizumab as monotherapy may have faded. Burgin et al note that eculizumab (900 mg/d) failed as treatment for advanced systemic atrophic papulosis with GI involvement, with fatality as the outcome.[46] Shapiro et al note that only two patients initially given eculizumab as monotherapy are still alive; they instead use a combination of subcutaneous treprostinil and eculizumab.[47] Eculizumab, if given early enough, may help abate malignant atrophic papulosis, but as monotherapy it is not instrumental in controlling it.  With four patients treated, there have had no deaths. The first two are now six-year survivors. Each of them had been critically ill in ICU settings prior to therapy. This information is important because malignant atrophic papulosis without treatment or hope of treatment is lethal and patients should be directed towards those experienced with treatment as eculizumab alone may not work.

Other reports[48] have supported the use of eculizumab for systemic Degos disease but informal communication to the author noted that despite treatment with eculizumab, some patients with systemic Degos disease have died. One report noted 2 patients with Degos disease in whom eculizumab failed.[49] One had overlapping lupus and the other had pulmonary hypertension. The pulmonary hypertension patient was treated with treprostinil and cutaneous MAP lesions resolved but disabling digital pain manifested. In the patient with Degos disease and lupus, treprostinil temporally resulted in clearing of hematuria, CNS symptoms and MRI finding improvements.

A presentation by Magro et al[50] reported that eculizumab, which has been approved for paroxysmal nocturnal hemoglobinuria, improved systemic Degos disease in 3 patients. This small series was uncontrolled, but the results suggest promise for eculizumab as a treatment. The effectiveness of eculizumab also may support the idea that Degos disease is not a collagen-vascular disease, but instead is an endothelial- or complement-mediated disease. Eculizumab is expensive, which may hinder its acceptance as widely used therapy.

An article published in 2013 found that exploratory treatment with eculizumab did not help the development or progression of Degos disease systemic manifestations,[51] with 5 of 7 patients’ disease initially improving but then regressing, with progression of disease in 1 immediately and the 4 others after a period of time.

A proposed new treatment for Degos disease is treprostinil, a medication for pulmonary hypertension. Shapiro et al (2013) report a series of 3 patients treated with subcutaneous treprostinil (dose not reported).[52] One patient had systemic lupus erythematosus (SLE), overlap scleroderma, extensive malignant atrophic papulosis lesions, and severe pulmonary hypertension without CNS or bowel involvement. She was placed on therapy with treprostinil for her pulmonary hypertension, but in the months subsequent to initiation of treatment, dramatic and complete resolution of cutaneous malignant atrophic papulosis–like lesions and disabling digital pain occurred. The second patient had pure malignant atrophic papulosis but progressive organ (CNS, bladder, neurological, and gross hematuria) dysfunction despite eculizumab treatment, but therapy with treprostinil was temporally associated with clearing of hematuria, resolution of CNS symptoms, and improvement in MRI findings.

Other treatments that have been tried without real effect include the following: topical corticosteroids, phenformin and ethylestrenol, iodohydroxyquinoline, aspirin and dipyridamole, phenylbutazone, arsenic, sulfonamides, dextran, corticosteroids, heparin, warfarin, niacin, streptomycin, corticotropin, azathioprine, methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, pentoxifylline, and clopidogrel.

Hohwy et al[40] treated a patient with fatal systemic malignant atrophic papulosis (MAP) with narrow-band ultraviolet (UVB) light and prednisolone and, later, with aspirin, pentoxifylline, and warfarin. Treatment was not effective. Interestingly, the patient has a mutation of factor V Leiden and lupus anticoagulant.

Care is primarily supportive. Admission to the hospital can be necessary in cases of gastrointestinal bleeding or other systemic complications.

Surgical Care

When gastrointestinal bleeding, intestinal perforation, bowel infarction, or intracranial bleeding occurs, proper surgical intervention is necessary.

Consultations

Consult the following physicians:

  • Dermatologists

  • Gastroenterologists

  • Neurologists

  • General surgeons

  • Neurosurgeons

  • Ophthalmologists

Activity

Patients are often weak and this limits their activity, but no limitation to Degos disease itself exists.

Long-Term Monitoring

Patients should be monitored for systemic manifestations of Degos disease and treated accordingly.

 

Medication

Medication Summary

For systemic Degos disease, the treatment of choice is eculizumab. The dosing of eculizumab is likely above the current FDA-approved dose for other conditions. Three cases of the successful use of eculizumab have been reported, and others likely exist. One aspect hindering use of eculizumab in Degos disease is the drug's high cost. Eculizumab is not a treatment for purely cutaneous Degos disease.

Some authorities have used antiplatelet medications, but their ultimate effect is unclear.

Anticoagulant

Class Summary

Eculizumab has been found to be a life saving drug for those with systemic Degos disease.

Eculizumab (Soliris)

This is an off-label use for Degos disease. Eculizumab blocks complement-mediated destruction of paroxysmal nocturnal hemoglobinuria red blood cells. It inhibits the C5 component of the complement system, thereby preventing the final stages of complement activation.

The drug is FDA approved to reduce hemolysis with paroxysmal nocturnal hemoglobinuria and for atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy.

Vasodilator

Class Summary

Prostacyclin is a strong vasodilator of all vascular beds and a potent endogenous inhibitor of platelet aggregation. Platelet effects result from activation of intracellular adenylate cyclase and from increased cyclic adenosine monophosphate (cAMP) concentrations within platelets. Prostacyclin may decrease thrombogenesis and platelet clumping in the lungs by inhibiting platelet aggregation.

Treprostinil (Tyvaso, Remodulin)

This is an off-label use for Degos disease. Treprostinil is a stable prostacyclin analogue. It elicits direct vasodilation of pulmonary and systemic arterial vessels and inhibits platelet aggregation. Vasodilation reduces right and left ventricular afterload and increases cardiac output and stroke volume.