Wernicke Encephalopathy Associated with Malabsorption in Degos Disease

Abstract

A 40-year-old female with systemic Degos disease presented with 4 days of confusion, somnolence, and ataxia. She was dependent on total parenteral nutrition (TPN) following ileocecectomy for Degos-related gastrointestinal complications and had recently transitioned from intravenous (IV) to oral thiamine supplementation. Although central nervous system involvement of Degos was initially suspected, magnetic resonance imaging findings, low thiamine levels, and rapid improvement with IV thiamine confirmed Wernicke’s encephalopathy. This case highlights the importance of recognizing nutritional deficiencies in TPN-dependent patients with neurologic symptoms, even in the context of a rare underlying disease.

Background

Malignant atrophic papulosis (MAP), or Degos disease, is a rare thrombo-obliterative vasculopathy with fewer than 200 cases reported worldwide. ¹ Although its etiology and pathophysiology remain poorly understood, the disease is broadly classified in 2 variants: a skin-limited form and a systemic form.^1,2 The hallmark skin lesions feature “porcelain-white” centers and erythematous, telangiectatic rims.^1,3 Diagnosis is based on the presence of pathognomonic skin lesions and histologic evidence of thrombotic occlusion in small arterioles. Central nervous system (CNS) involvement occurs in up to 60% of systemic cases and typically manifests with nonspecific symptoms, including headache, focal neurologic deficits, and encephalopathy.^4,5 CNS involvement is confirmed by characteristic findings on brain imaging.^1,6 Currently, there is no definitive treatment for either the cutaneous or systemic forms of Degos disease. ²

Case Report

A 40-year-old female with a history of anxiety, insomnia, gastroesophageal reflux, chronic pain, paroxysmal atrial fibrillation, and systemic Degos disease presented with 4 days of unsteady gait, somnolence, and confusion. She was diagnosed with Degos disease 3 years prior to admission based on a skin biopsy and dermatologic evaluation. Treatment with eculizumab was initiated; however, her course was complicated by bowel perforations requiring multiple surgical interventions, ultimately resulting in a high-output enterocutaneous fistula and long-term dependence on total parenteral nutrition (TPN) following an ileocecectomy. Her medications included duloxetine, loratadine, metoprolol, morphine, pantoprazole, trazadone, aspirin, olanzapine, sildenafil, thiamine, and eculizumab. Three months prior to presentation, a shortage of intravenous (IV) thiamine for TPN forced her to rely solely on oral thiamine supplementation.

She initially presented to an outside hospital, where she was noted to have episodes of confusion, somnolence, and incoherent speech. Initial labs showed elevated lactic acid, elevated alkaline phosphate, thrombocytopenia, a urinalysis with moderate leukocytes, trace ketones, 5 to 10 red blood cells, 5 to 10 white blood cells, 1+ bacteria, a urine drug screen positive for benzodiazepines, a low thyroid stimulating hormone level, and an otherwise unremarkable complete blood count, comprehensive metabolic panel, free T4 (FT4) level, and serum ethanol level.

Due to concern for CNS involvement of Degos versus sepsis, cultures were obtained, she underwent computed tomography (CT) imaging, and was started on broad coverage antibiotic therapy. Her head CT without contrast showed no pathologic findings. She was admitted and underwent brain magnetic resonance imaging (MRI), which showed symmetric T2 FLAIR hyperintensity of the mamillary bodies, tegmentum, and cerebral aqueduct suggestive of Wernicke’s encephalopathy (Figure 1). Her serum thiamine level returned low at 21.1 nmol/L (reference range 66.5-200 nmol/L), and she was started on thiamine 500 mg IV 3 times daily. She was transferred to our hospital for further care.

Figure 1.

Brain MRI with symmetric T2 FLAIR hyperintensity of the mamillary bodies (yellow arrows), tegmentum, and cerebral aqueduct (red arrow). MRI, magnetic resonance imaging.

On arrival, she was afebrile and hemodynamically stable. Her examination demonstrated visual hallucinations, bilateral vertical and horizontal nystagmus, and marked impairment in gait stability and balance, requiring a rolling walker. Otherwise, she had intact attention, preserved short- and long-term memory, fluid and coherent speech, normal sensation to light touch, no focal weakness, normal reflexes, and appropriate responses to questions. Dermatologic examination revealed numerous papules characterized by central porcelain-white atrophic zones and erythematous rims, distributed across the extremities and trunk. Further infectious, autoimmune, and paraneoplastic work-up was negative. ¹ Additional labs showed hypoalbuminemia, and deficiencies in vitamin B6, vitamin D, zinc, and selenium (Table 1).

Table 1.

Laboratory Findings.

Test	Result	Reference range
Laboratory results from initial presentation
Platelets, ×109/L	88	150-350
Albumin, g/dL	3.0	3.4-5.0
TSH, µIU/mL	0.06	0.45-5.33
FT4, ng/dL	0.94	0.61-1.12
Urine toxicology	Benzodiazepine positive	Negative
Alkaline phosphatase, U/L	148	30-105
Lactate, mmol/L	4.8	0.5-2.0
Thiamine, nmol/L	21.1	66.5-200.0
Additional laboratory results
Autoimmune/paraneoplastic evaluation, serum a	Negative	Negative
CRP, mg/dL	7	<10
ESR, mm/h	7	0-20
Ammonia, µmol/L	20	11-32
Salicylate, mg/dL	<2.5	2.5-20
Parvovirus B19 IgG	Positive	Negative
Parvovirus B19 IgM	Negative	Negative
HIV antigen/antibody	Negative	Negative
Vitamin B6, mcg/L	2	5-50
Vitamin B12, pg/mL	330	211-911
Vitamin A, mcg/dL	56.7	32.5-78
Vitamin D, ng/mL	9.3	20.0-80.0
Vitamin E, mg/L	8.6	5.5-17
Vitamin K1, ng/mL	0.41	0.10-2.20
Manganese, ng/mL	0.7	0.5-1.2
Zinc, µg/dL	54	60-106
Copper, µg/dL	83	77-206
Selenium, µg/dL	87	110-165

Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FT4, free T4; HIV, human immunodeficiency virus; TSH, thyroid-stimulating hormone.

a

Gaba-B-R, AMPA receptor, amphiphysin serum, antiglial/neuronal nuclear autoantibody-type, antineuronal nuclear types 1, 2, and 3, contactin-associated protein-2 IgG, collapsin response-mediator protein-5 (CRMP-5) neuronal IgG, dipeptidyl aminopeptidase-like protein 6, glutamic acid decarboxylase 65 (GAD65), glial fibrillary acidic protein, anti-immunoglobulin-like cell adhesion molecule 5, leucine-rich glioma inactivated 1 protein, metabotropic glutamate receptor 1, neurochondrin-IgG, neuronal intermediate filament, NMDA receptor, Purkinje cell cytoplasmic types 1 and 2 antibodies, and septin-7 antibody tests.

During hospitalization, the patient received thiamine at a dose of 500 mg IV 3 times daily for 2 days, followed by 250 mg daily for an additional 2 days. Thiamine was subsequently incorporated into her TPN at 180 mg/day thereafter. Following high-dose thiamine repletion, her nystagmus and ataxia resolved.

Dermatology was consulted, and the cutaneous findings were determined to be characteristic of her underlying systemic Degos disease. No additional diagnostic evaluation, biopsy, or topical therapy was recommended.

The patient’s thrombocytopenia was of new onset compared with prior laboratory values. Her platelet count initially declined, reaching a nadir of 29 × 10⁹/L. Following an extensive diagnostic evaluation, hematology attributed the thrombocytopenia to nutritional deficiency. Over the course of her hospitalization and subsequent outpatient follow-up, her platelet count improved and stabilized within normal limits.

Her disorientation and visual hallucinations improved but persisted at discharge. Though Degos-related CNS involvement was initially suspected, her clinical course supported Wernicke’s encephalopathy as the primary etiology.

Discussion

MAP, or Degos disease, is an exceptionally rare, chronic thrombo-obliterative vasculopathy. Current literature estimates the mean age of disease onset to be 35.4 ± 12.3 years, with greater prevalence among women. MAP presents in 2 recognized phenotypes: a benign, skin-limited form and a systemic form with multisystem involvement. ³ In both forms of Degos disease, diagnosis is based on clinical evidence of pathognomonic papules 2 to 15 mm in diameter with central “porcelain-white” atrophy and peripheral telangiectatic rims, distributed on the trunk and upper extremities (Figure 2).^2,7 The diagnosis is confirmed by characteristic histopathologic features on skin biopsy, including an atrophic epidermis, endothelial hyperplasia with monocytic infiltrates in the dermis, and lymphocyte-associated necrotic vasculitis characterized by intimal thickening from thrombosis and possible adventitial inflammation. ² Although the underlying etiology of Degos disease remains uncertain, interferon-alpha and complement C5 deposition have been implicated in the vascular pathology. ³

Figure 2.

Classic Degos skin lesions with “porcelain-white” centers and telangiectatic red rims. ⁷

In systemic Degos disease, in addition to the characteristic cutaneous lesions, internal organs such as the gastrointestinal (GI) tract, CNS, pleura, and pericardium may be affected. ⁵ Systemic MAP carries high morbidity and mortality—estimated up to 50% in 2 to 3 years. ⁶ Up to 50% of patients with systemic Degos disease have GI involvement. Thrombotic lesions in the GI tract can lead to infarctions that present as peritonitis or recurrent bowel perforations. Among patients with systemic MAP, these GI manifestations represent the leading cause of death. ⁸ While both laparoscopy and endoscopy have been employed to detect GI involvement in Degos disease, evidence suggests that laparoscopy may serve as a more reliable indicator of systemic progression, particularly in cases where endoscopic findings are unremarkable. ⁹

CNS involvement is reported in 20% to 60% of patients with systemic Degos disease. ⁶ Current literature shows a wide range of neurologic manifestations, including headache, dizziness, seizure, aphasia, paraplegia, cranial nerve deficits, polyradiculoneuropathy, and ophthalmoplegia.^5,6,8 CNS involvement is confirmed by brain MRI, which reveals diffuse leptomeningeal enhancement within the basal cisterns and sylvian fissures, along with evidence of small-vessel infarcts.^5,6 Autopsy findings often reveal small-vessel infarcts and hemorrhages without overt thrombosis. ¹⁰ There is no definitive cure for either the cutaneous or systemic variants of Degos disease. While anti-platelet agents may provide some benefit for cutaneous involvement, treatments such as immunosuppressants, plasmapheresis, and anti-inflammatory agents have not proven effective.^3,11,12

Wernicke’s encephalopathy is an acute neurological condition caused by thiamine (vitamin B1) deficiency. Though classically associated with chronic alcohol use, it also arises from malnutrition, hyperemesis, bariatric surgery, or TPN without proper supplementation. Classic features of ophthalmoplegia, ataxia, and confusion, may be absent or incomplete. Characteristic brain MRI findings include T2 hyperintensity in the mammillary bodies, periventricular gray matter, thalamus, inferior colliculi, and fornix. Prompt recognition and thiamine replacement are essential to alleviate symptoms and prevent progression to Korsakoff syndrome and irreversible brain injury. Many patients with Wernicke’s encephalopathy can experience partial or full recovery of lost CNS function with timely thiamine replacement.

Our patient was diagnosed with systemic Degos disease by skin biopsy 3 years prior to this admission. Since then, she had developed multiple complications related to GI involvement, resulting in TPN dependence. At the time of presentation, she exhibited confusion, ophthalmoplegia, and ataxia. Given her history of systemic Degos disease, CNS involvement was an initial and important consideration. The differential also encompassed a broad range of acute neurologic processes, including CNS infection, acute vascular occlusion, metabolic or nutritional deficiencies, medication-related effects, toxic exposures, and inflammatory disorders. However, several factors ultimately argued against Degos-related pathology or any of the other proposed etiologies. Neuroimaging lacked the imaging findings typical of Degos or other structural causes, there were no recent medication changes or toxin or substance exposures, and no evidence to support infectious or inflammatory conditions. In contrast, the presence of marked thiamine deficiency, the alignment of her symptoms with known manifestations of thiamine depletion, and her rapid clinical improvement following IV thiamine administration strongly supported Wernicke’s encephalopathy as the underlying diagnosis. ⁵ While no direct association between Degos disease and Wernicke’s encephalopathy has been reported, thiamine deficiency due to TPN dependence is a recognized cause of Wernicke’s. ¹³

This case report describes a unique instance of Wernicke’s encephalopathy in a patient with systemic Degos disease. It underscores the need for careful consideration of nutritional deficiencies in patients with complex GI pathology and dependence on TPN. Importantly, it highlights how familiar, treatable conditions like thiamine deficiency can present with symptoms mimicking rare neurologic syndromes and reinforces the value of neuroimaging in differentiating CNS pathologies. Timely recognition and thiamine repletion likely prevented irreversible damage in this case.