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LETTERS TO THE EDITOR
Year : 2021  |  Volume : 24  |  Issue : 6  |  Page : 1005-1009
 

Clinico-pathological features in köhlmeier–degos disease with cutaneous and neurological involvement


1 Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
2 Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
3 Department of Dermatology, St John's Medical College Hospital, Bangalore, Karnataka, India
4 Department of Neurology, Columbia Asia Hospital, Bangalore, Karnataka, India
5 Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India

Date of Submission19-Sep-2020
Date of Acceptance03-Nov-2020
Date of Web Publication27-Mar-2021

Correspondence Address:
Dr. Sanjib Sinha
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aian.AIAN_1004_20

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How to cite this article:
Sindhu DM, Shivaram S, Rao S, Nagappa M, Seshagiri DV, Santosh V, Madhukara J, Shreedhara A S, Bhat MD, Bharath RD, Sinha S. Clinico-pathological features in köhlmeier–degos disease with cutaneous and neurological involvement. Ann Indian Acad Neurol 2021;24:1005-9

How to cite this URL:
Sindhu DM, Shivaram S, Rao S, Nagappa M, Seshagiri DV, Santosh V, Madhukara J, Shreedhara A S, Bhat MD, Bharath RD, Sinha S. Clinico-pathological features in köhlmeier–degos disease with cutaneous and neurological involvement. Ann Indian Acad Neurol [serial online] 2021 [cited 2022 Jul 1];24:1005-9. Available from: https://www.annalsofian.org/text.asp?2021/24/6/1005/312439




Sir,

Köhlmeier–Degos disease or Degos disease or malignant atrophic papulosis is a rare chronic obliterative vasculopathy of uncertain etiology. It affects skin and other organs such as the gastrointestinal tract and the central nervous system, in addition to the heart, lungs, kidneys, and eyes.[1] It can be classified as (i) malignant Degos disease with systemic manifestations which is further subclassified as (a) autoimmune: when there are associated clinical and/or laboratory features of either connective tissue disease or vasculitis, (b) coagulopathy-associated, and (c) virally induced, and (ii) benign cutaneous type which lacks systemic manifestations even after years of onset.[1] The disease usually manifests in adults, has male preponderance, and has been more commonly reported from the Caucasian population.[1] We describe the clinical course in a patient with Degos disease having neurological involvement and highlight the imaging and histological findings.

A 44-year-old gentleman developed one episode of focal-to-bilateral tonic–clonic seizure. Examination four hours after the seizure was normal. He had diffuse skin lesions for about 2 years [Figure 1]a and [Figure 1]b. He did not have preexisting scarring acne on the face. Brain MRI showed enhancing multifocal T2/FLAIR hyperintense lesions [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]g. Stereotactic biopsy of the right temporal lesion showed areas of coagulative necrosis/infarct which was indicative of vasculopathy/vasculitic process [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Brain MRI after 2 months showed an increase in the size of the lesions [Figure 1]h, [Figure 1]i, and [Figure 1]j. The histopathological findings of skin biopsy are depicted in [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d. He was treated empirically with intravenous methyl prednisolone (1 g/day for 5 days). One month later, he developed sudden onset, non-progressive, impaired vision in the right eye. Examination revealed bilateral optic disc edema, soft retinal exudates, and right inferior temporal quadrantanopia. Brain MRI done 4 days after the onset of new deficits showed no new lesions. There was evidence of “blooming” in susceptibility-weighted images within these lesions [Figure 1]k and [Figure 1]l. Hematological and biochemical investigations were significant for an elevated erythrocyte sedimentation rate (52 mm/first hour). Work up for immune-mediated and granulomatous disorders and serological testing for human immunodeficiency virus, hepatitis B, and hepatitis C viruses were negative. Cerebrospinal fluid analysis showed normal opening pressure and slightly elevated protein (50.9 mg/dL, ref.: 15–45 mg/dL). CT scan of chest and abdomen was normal. Based on the clinical and histological findings of the characteristic skin lesions, the patient was diagnosed to have Degos disease. He was treated with monthly pulsed intravenous methylprednisolone along with levetiracetam, clopidogrel, and cilostazole. His visual deficits remained status quo. There was no recurrence of seizures. Skin lesions increased in number. He developed gastrointestinal symptoms in the form of vomiting and diarrhea alternating with constipation and he succumbed to his illness around one year after onset of neurological symptoms.
Figure 1: (a, b) Clinical photographs showing papular skin lesions with a porcelain-white center and erythematous margin over the posterior aspect of trunk and limbs. (c–e) Axial sections of brain MRI show hyperintense lesions in the right frontal and posterior temporal and left parietal in T2 sequences. (f and g) Postcontrast T1W sequences show enhancement of the periphery of lesions. (h,i, and j) Brain MRIs after 2 months of onset show increase in the size of the lesions. (k and l) Blooming seen on SWI within the lesions. (m–q) Brain MRI after the onset of visual symptoms shows persistence of the lesions

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Figure 2: (a) Biopsy of the right posterior temporal brain lesion shows thickened leptomeningeal vessel with perivascular inflammation (H&E, 100×). (b and c) Cortical vessels with fibrin thrombus (arrow) and vessel wall inflammation (H&E, 200×). (d) Thrombosed vessel with parenchymal infarct (H&E, 200×)

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Figure 3: (a) Biopsy of skin shows thinned out epidermis (H&E, 100×). (b) Basal layer shows vacuolation (H&E, 200×). (c) Inflammatory infiltrate with karryorhectic debris is noted (H&E, 200×). (d) A dermal vessel shows sclerosis and damage to the wall (H&E, 200×)

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Neurological involvement is reported in 20–60% of patients with Degos disease.[2] In a case series from the Mayo Clinic, 10 out of 15 patients had neurological manifestations, including fatal hemorrhagic or ischemic strokes, polyradiculoneuropathy, and nonspecific symptoms. More than half the patients had only cutaneous manifestations.[3] As noted in our patient, the skin lesions antedate neurological manifestations by weeks to years. Uncommonly, neurological features can precede or occur simultaneously with skin lesions.[4] Any part of the neuraxis can be affected and the clinical manifestations correspond to the site of involvement. Our patient manifested with neurological and ophthalmological features in the form of seizures, quadrantanopia, and multifocal brain lesions, which were secondary to vasculopathy of the leptomeningeal and cortical vessels. He also developed optic disc edema in the absence of raised intracranial pressure raising the possibility of optic nerve head ischemia secondary to retinal artery involvement. [Table 1] summarizes the neurologic manifestations reported in literature.[2],[3],[4],[5],[6],[7],[8],[9]
Table 1: Neurologic manifestations of Degos disease reported in literature

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The clinical course is progressive, sometimes fulminant, with the appearance of new neurological deficits as was noted in our patient. Fatal outcome has been reported in majority of the patients.[5],[7] Death occurs from bowel perforation, large cerebral infarcts, or massive cerebral hemorrhage. Rarely patients have mild or transient deficits.[10] The key determinant of mortality is the degree of vascular involvement and ischemic complications. The factors that determine whether the disorder remains benign and confined to the skin or becomes malignant with other organ system involvement are not known.

Establishing an early and accurate diagnosis is important to ensure close follow-up for extracutaneous organ involvement. Diagnosis rests on identifying the characteristic skin lesions as noted in our patient, which is further supported by histological studies. Other neurological disorders where cutaneous lesions aid in the etiological diagnosis are listed in [Table 2]. Treatment of Degos disease includes immunosuppressive agents, antiplatelets, anticoagulants, rheological agents, and prostaglandins like treprostinil.[1] There is no effective treatment for Degos disease since the understanding of the underlying pathophysiology is incomplete. Increased platelet aggregation and fibrinolytic dysfunction have been noted.[1] Familial occurrence with autosomal dominant inheritance has been reported. Autoimmunity appears to play a major role as evidenced by presence of autoantibodies like antiphospholipid antibodies. Besides, as noted in our patient, histopathological findings of the skin and brain suggest vasculopathy. Other studies including autopsy-based studies provide evidence for obstructive vasculopathy of small and medium-sized vessels, with variable degree of inflammation, sparing the tunica media.[2] Histological changes in the skin evolve in early, fully developed, and late lesions.[1] Based on the available evidence, various mechanisms have been proposed to explain the clinical manifestations of this disease including vasculitis, coagulopathy, and endothelial dysfunction triggered by viral or bacterial infections.[1] How the interplay of genetics, autoimmunity and coagulopathy drives the disease process and contributes to the obstructive vasculopathy of Degos disease still remains to be understood.
Table 2: Differential diagnosis of central nervous system disorders with pathognomonic skin lesions

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We highlight the clinical, radiological, and histological findings in a patient with systemic Degos disease and stress on meticulous skin examination as a crucial step in the diagnostic algorithm. It is important to establish an accurate diagnosis for counseling the patient regarding the prognosis. Knowledge gaps in the disease pathophysiology need to be filled so as to develop effective targeted therapies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Theodoridis A, Makrantonaki E, Zouboulis CC. Malignant atrophic papulosis (Köhlmeier-Degos disease)-A review. Orphanet J Rare Dis 2013;8:10.  Back to cited text no. 1
    
2.
Amato C, Ferri R, Elia M, Cosentino F, Schepis C, Siragusa M, et al. Nervous system involvement in Degos disease. AJNR Am J Neuroradiol 2005;26:646-9.  Back to cited text no. 2
    
3.
Subbiah P, Wijdicks E, Muenter M, Carter J, Connolly S. Skin lesion with a fatal neurologic outcome (Degos' disease). Neurology 1996;46:636-40.  Back to cited text no. 3
    
4.
Ye L, Lekgabe E, Tsui A, Gaillard F. The evolution of cerebrovascular changes in Köhlmeier-Degos disease: An 11-year follow-up case report. J Clin Neurosci 2018;48:114-7.  Back to cited text no. 4
    
5.
Dastur DK, Singhal BS, Shroff HJ. CNS involvement in malignant atrophic papulosis (Kohlmeier-Degos disease): Vasculopathy and coagulopathy. J Neurol Neurosurg Psychiatry 1981;44:156-60.  Back to cited text no. 5
    
6.
Caviness Jr VS, Sagar P, Israel EJ, Mackool BT, Grabowski EF, Frosch MP. Case 38-2006: A 5-year-old boy with headache and abdominal pain. N Engl J Med 2006;355:2575-84.  Back to cited text no. 6
    
7.
Moss C, Wassmer E, Debelle G, Hackett S, Goodyear H, Malcomson R, et al. Degos disease: A new simulator of non-accidental injury. Dev Med Child Neurol 2009;51:647-50.  Back to cited text no. 7
    
8.
Yeo TH, Vassallo G, Judge M, Laycock N, Kelsey A, Crow YJ. Infantile neurological Degos disease. Eur J Paediatr Neurol 2011;15:167-70.  Back to cited text no. 8
    
9.
Matsuura F, Makino K, Fukushima T, Matsubara N, Shibuya M, Higuchi T, et al. Optic nerve and spinal cord manifestations of malignant atrophic papulosis (Degos disease). J Neurol Neurosurg Psychiatry 2006;77:260-2.  Back to cited text no. 9
    
10.
Sharma S, Brennan B, Naden R, Whelan P. A case of Degos disease in pregnancy. Obstet Med 2016;9:167-8.  Back to cited text no. 10
    


    Figures

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    Tables

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