lipoid proteinosis

Radiopaedia • CC-by-nc-sa 3.0 • de

Urbach-Wiethe disease, also known as lipoid proteinosis or hyalinosis cutis et mucosae, is a rare autosomal recessive genodermatosis that primarily affects the skin, upper respiratory tract, and central nervous system (CNS).

Epidemiology

Urbach-Wiethe disease is a very rare condition, with fewer than 500 cases having been reported . From these cases, it seems to affect males and females equally, and has been described to be most prevalent in certain families in South Africa, the Middle East, and Europe .

Clinical presentation

Urbach-Wiethe disease has a varying phenotype that develops over time, but generally initially manifests in infancy or early childhood . Although the skin, upper respiratory tract, and central nervous system (particularly the amygdala) are the most commonly affected regions of the body, any body system may be involved .

Common clinical features include:

  • skin
    • initially, increased susceptibility to trauma, recurrent impetigo that is often bullous
    • over time skin thickening develops, most evident on the face and in skin folds
    • this progresses to development of multiple waxy papules, nodules and plaques, especially at sites of friction (e.g. elbows) 
      • one pathognomonic lesion is moniliform blepharosis which describes multiple papules along the eyelid margins and inner canthus
    • alopecia may also eventually develop
  • head and neck
    • initially, a hoarse cry in infancy due to vocal cord stiffening, this is often the first clinical feature of the disease
    • over time thickened white oral mucosa (causing macroglossia, cobblestone lips, etc.) develops, these may be accompanied by mouth ulcerations
    • dysphagia, persistent hoarseness, recurrent upper respiratory tract infections, recurrent parotitis, and recurrent dental infections may further manifest
  • CNS
    • memory loss
    • temporal lobe epilepsy
    • psychiatric features (e.g. absence of fear, hallucinations, delusions), these are in addition to potential secondary psychological effects of the skin manifestations (e.g. social anxiety, depression) 
    • dystonia
    • mentation may be normal or impaired, and may decline over time

Pathology

Urbach-Wiethe disease is an autosomal recessive disorder caused by mutations in the ECM1 gene on chromosome 1, which encodes extracellular matrix protein 1 (ECM1) . ECM1 is a key structural component of basement membranes and the extracellular matrix, providing strength to tissues . Furthermore, it may also have roles in differentiation of various cell lines and angiogenesis .

Patients with mutations to both ECM1 genes produce a dysfunctional ECM1 or do not produce it at all, resulting in an unstable and weakened basement membrane and extracellular matrix . Thus, Urbach-Wiethe disease is characterized by deposition of hyaline material within and adjacent to the basement membranes, particularly of capillaries . As the disease progresses, there is infiltration and destruction of the surrounding tissues which results in the typical clinical presentation of the disease .

It has been postulated that these hyaline proteins are over-produced by surrounding tissues as either part of the body’s response to, or intrinsically because of, the weakened basement membrane and extracellular matrix . It is unclear why some parts of the body (e.g. skin, amygdala, oropharyngeal mucous membranes) are affected more than others in this disease.

Radiographic features

CT

In keeping with the clinical presentation, brain CT typically demonstrates bilateral symmetric horn-shaped mesial temporal lobe intracranial calcifications, characteristically affecting the amygdala and not exerting any mass effect . These calcifications are seen in 50–75% of cases in affected patients over 10 years of age .

MRI 

Brain MRI allows for visualization of the same calcifications in the mesial temporal lobes, although is generally less sensitive to these changes . However, there are no case reports describing the use of SWI, which may be more sensitive to these calcifications.

Described signal changes of the mesial temporal lobes are therefore consistent with calcification :

  • T1: usually hypointense
  • T2: hypointense
  • GRE: hypointense

Treatment and prognosis

There is no curative therapy available, and management is therefore focused on symptomatic relief. Prognosis is variable depending on the level of CNS dysfunction and involvement of other organs but can be normal.

History and etymology

The condition was first described by Austrian physicians Erich Urbach (1893-1946) and Camillo Wiethe (1889-1949), in 1929 . Of the cases described since then, one case of a patient "S.M." described in 1994 has garnered notable attention in the media in relation to the patient's absence of fear, one of the characteristic CNS manifestations of the disease .

Differential diagnosis

Siehe auch:
und weiter: