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Year : 2022  |  Volume : 67  |  Issue : 4  |  Page : 482
A xanthomatous eruption in a patient with jaundice and constitutional symptoms


1 From the Department of Dermatology, Universitat de Barcelona, Barcelona, Spain
2 Dermatopathology, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain

Date of Web Publication2-Nov-2022

Correspondence Address:
Josep Riera-Monroig
Department of Dermatology, Hospital Clínic de Barcelona, Villarroel 170. 08036, Barcelona
Spain
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_1162_20

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How to cite this article:
Serra-García L, Castillo P, Iranzo P, Riera-Monroig J. A xanthomatous eruption in a patient with jaundice and constitutional symptoms. Indian J Dermatol 2022;67:482

How to cite this URL:
Serra-García L, Castillo P, Iranzo P, Riera-Monroig J. A xanthomatous eruption in a patient with jaundice and constitutional symptoms. Indian J Dermatol [serial online] 2022 [cited 2022 Dec 8];67:482. Available from: https://www.e-ijd.org/text.asp?2022/67/4/482/360305




A 79-year-old woman with a two-year history of unexplained progressive cholestasis was admitted to the hospital suffering from jaundice, abdominal pain, constitutional symptoms, and pruritus. The patient was seen in dermatology because of pruriginous skin lesions. Physical examination revealed multiple presternal yellowish papules on an erythematous base coalescing into a V-shaped plaque, with surrounding scattered yellowish papules [Figure 1].
Figure 1: Erdheim-Chester disease presenting as an eruptive xanthoma. (a) Multiple yellowish papules over an erythematous base coalescing into a V-shaped plaque in the presternal region. (b) Scattered yellowish-erythematous papules and plaques scattered over the trunk, some showing superficial erosion

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Laboratory investigations showed cholestasis: gamma-glutamyltransferase 697 U/L (reference values, RV, 5-40), total bilirubin 8.0 mg/dL (RV <1.2), direct bilirubin 6.2 mg/dL (RV <0.6), and alkaline phosphatase 1342 U/L (RV 46-116). Total cholesterol levels were 427 mg/dL (RV <200) and triglycerides were 175 mg/dL (RV <150).

A skin biopsy revealed a dermal circumscribed infiltrate with foamy and fusocelular histiocytes, which were CD68-positive, langerin and CD1a-negative [Figure 2]. Imaging studies showed increased axial skeleton metabolic activity [Figure 3]. The BRAF V600E mutation was present in blood, skin, and bone specimens.
Figure 2: Histopathological findings in the skin biopsy. (a) Hematoxylin-eosin stain showing a circumscribed dense dermal infiltrate with foamy and fusocelular histiocytes (original magnification x100). (b) CD68 immunohistochemical stain positive for histiocytic infiltrate (original magnification ×100). (c) Negative CD1a immunohistochemical stain (original magnification ×100)

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Figure 3: Increased axial skeleton metabolic activity. Positron emission tomography showing increased axial bone metabolic activity measured by fluorodeoxyglucose F 18 tissue uptake. Images are fused with computerized tomography scans (PET-CT) for improved definition

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What is Your Diagnosis?

Diagnosis:

Erdheim–Chester Disease.


   Discussion Top


Erdheim–Chester Disease (ECD) is a rare non-Langerhans cell histiocytosis first described by Jakob Erdheim and his pupil William Chester in 1930. It predominantly affects 50- to 60-year-old adults and is characterized by tissue infiltration with foamy CD68-positive and CD1a-negative histiocytes against a background of inflammatory stroma.[1] ECD can affect virtually any tissue or organ, because it is a multisystemic disease with characteristic skeletal involvement, cardiovascular disease, and retroperitoneal fibrosis, among other conditions.[2] Cutaneous involvement is present in one third of patients, and represents the first sign of the disease in 30% of these. Periorbital xanthelasma-like lesions are the most frequent and considered specific. However, a wide variety of cutaneous manifestations have been described, including papulonodular erythematous and tumoral lesions and brown patches.[3] Skin lesions may give a clue to diagnosis, which requires characteristic histopathological features and immunophenotype in an appropriate clinical and radiological context.[2]

During the past decade, advances have been made in the understanding of ECD pathophysiology. The recent discovery of BRAF V600E mutation in more than 50% of these patients as well as other mutations in genes implicated in the MAPK activation pathway has broadened knowledge of this disease and other histiocytoses, such as Langerhans-cell histiocytosis.[4] These mutations have been associated with oncogene-induced senescence, a process in which activation of a specific oncogene leads to cell cycle arrest and induction of pro-inflammatory molecules, instead of cell proliferation.[1]

Until 2012, the main therapeutic regimens were based on interferon alfa, which had demonstrated prolonged survival, and other chemotherapy regimens. The recent introduction of BRAF inhibitors, such as vemurafenib has revolutionized the treatment of ECD, with response rates in 88% of patients, lower mortality rates, and increased overall survival.[4] Given its excellent results, this therapy has recently been approved by the FDA and EMA for the treatment of ECD.[5]

Diagnosis of ECD can be challenging. Dermatologists should take ECD into considerantion in the differential diagnosis of eruptive xanthoma-like lesions, because it can be the first sign of the disease and key to an early diagnosis of this multisystemic disease.


   Learning Points Top


  • Erdheim–Chester disease is a non-Langerhans cell histiocytosis characterized by tissue infiltration with foamy histiocytes that are CD68-positive, langerin and CD1a-negative.
  • It is a multisystemic disease with characteristic skeletal, cardiovascular, retroperitoneal, and skin involvement.
  • Cutaneous manifestations are present in one third of patients and can be the first sign of presentation.
  • Periorbital xanthelasma-like lesions are the most frequent cutaneous sign and are considered specific, but many other skin lesions have been described.
  • Mutations in the BRAF V600E gene have been described in more than 50% of patients with BRAF inhibitors, such as vemurafenib emerging as successful treatments.


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.
Campochiaro C, Tomelleri A, Cavalli G, Berti A, Dagna L. Erdheim-Chester disease. Eur J Intern Med 2015;26:223-9.  Back to cited text no. 1
    
2.
Estrada-Veras JI, O'Brien KJ, Boyd LC, Dave RH, Durham BH, Xi L, et al. The clinical spectrum of Erdheim-Chester disease: An observational cohort study. Blood Adv 2017;1:357-66.  Back to cited text no. 2
    
3.
Chasset F, Barete S, Charlotte F, Cohen-Aubart F, Arnaud L, Le Pelletier F, et al. Cutaneous manifestations of Erdheim-Chester disease (ECD): Clinical, pathological, and molecular features in a monocentric series of 40 patients. J Am Acad Dermatol 2016;74:513-20.  Back to cited text no. 3
    
4.
Haroche J, Cohen-Aubart F, Rollins BJ, Donadieu J, Charlotte F, Idbaih A, et al. Histiocytoses: Emerging neoplasia behind inflammation. Lancet Oncol 2017;18:e113-25.  Back to cited text no. 4
    
5.
Diamond EL, Subbiah V, Lockhart AC, Blay J-Y, Puzanov I, Chau I, et al. Vemurafenib for BRAF V600–Mutant Erdheim-Chester disease and langerhans cell histiocytosis: Analysis of data from the histology-independent, phase 2, open-label VE-BASKET study. JAMA Oncol 2018;4:384-8.  Back to cited text no. 5
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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