Lipoid proteinosis / Urbach-Wiethe disease

DR. R.SURESH KUMARRADIOLOGY PGSvs medical collegeMahabubnagarAP

Urbach-Wiether disease (named after Erich Urbach and Camilo Wiethe)

synonyms: “lipoid protenoisis” or “hyalinosis cutis et mucosae”

Lipoid proteinosis (LP) or Urbach-Wiethe disease rare genodermatosis characterized by multisystem involvement due to intracellular deposition of an amorphous hyaline material

FrequencyInternationalVery rare and till date not more than 500 cases have been reported from all over the world

Mortality/MorbidityLife span is usually normal unless altered by laryngeal obstruction or epilepsy. Patients with significant airway compromise may require permanent tracheostomy

RacePatients of European ancestry are most commonly affected, including South African descendants of German or Dutch immigrants

Urbach-Wiether is a disease not a syndrome

a genetic mutation in chromosome 1 inherited in autosomal recessive fashion that explains all of the symptoms of the condition

Both sexes are affected equally

The mutation affects a protein in the extracellular space (also called matrix) that is present in all tissues and organs.  

A glycoprotein produced by the normal ECM1 gene is expressed in skin, mucosa and the entire human viscera

Mutation in this gene leads to deposition ofhyaline like material in the skin and viscera in abnormal amounts which is the cause of clinical manifestations.

Segment of the long arm of Chromosome 1, where the ECM1 mutation occurs at 1q21.

LP is caused by mutations in the extracellular matrix protein 1 (ECM1) gene

•AgePatients typically present in early childhood, but manifestations may be present at birth Some cases may occur in adults. Adults may have subtle skin findings and may present with complications due to visceral deposition

•HistoryA weak or hoarse cry from birth or starting in early infancy is typical and remains throughout life

•Cutaneous manifestations usually arise during the first 2 years of life

Recurrent , variable sized , vesicles, pustules, bullae and hemorrhagic crusts

Resolution of the lesions occurs with permanent, poxlike atrophic scarring.Resolution of the lesions occurs with permanent, poxlike atrophic scarring.Resolution of the lesions occurs with permanent, poxlike atrophic scarring.

Resolution of the lesions occurs with permanent, poxlike atrophic scarring.

face and distal extremities are the most common sites

EARLY SKIN MANIFESTAIONS

• skin develops a waxy, thickened, yellowish appearance due to dermal infiltration

•Papules, plaques, and nodules arise on the face, axillae, and scrotum

LATE SKIN MANIFESTATIONS

•Moniliform blepharosis

A pathognomonic sign is a row of beaded papules along the eyelid margins, resembling a string of pearls; this is termed moniliform blepharosis

beaded papules along the eyelids (moniliform blepharosis) and partially missing eyelashes

Beading (the formation of nodules) around the eyelids is common 

Hyperkeratotic, verrucous plaques may arise in sites of trauma, particularly the elbows, knees, and dorsum of the hands

Waxy plaques on elbows resembling xanthomas

ORAL CAVITY

•Pebbling of the lip mucosa imparts a cobblestone appearance, which may also involve the tongue and gingiva

•Infiltration of the tongue and frenulum results in a woody firmness and impaired mobility

Thickening of frenulum

•Hypoplasia or aplasia of the teeth, particularly the lateral incisors and premolars, may occur

•Recurrent parotitis may occur as a consequence of infiltration of the Stensen duct.

Transient swelling and ulceration of the lips and tongue

 

Infiltration of the larynx, vocal cords, and surrounding structures may produce hoarseness, dysphagia, and airway obstruction

UPPER AIRWAY

CENTRAL NERVOUS SYSTEM

A classic and pathognomonic radiographic finding is bilateral, intracranial, bean-shaped suprasellar calcifications in the temporal lobe

Amygdalae involvement is considered pathognomonic, being more prominent with longer disease duration

Most commonly affected sites are • Amygdalae•Hippocampus• Parahippocampal gyrus or even the Striatum

Rare Brain Disorder Prevents All Fear

Curvilinear hyperattenuated horn-shaped lesions are well depicted by CT in the amygdaloid bodies

On MR imaging, such lesions are hypointense in all pulse sequences, especially in GRE T2* weighted images

Axial plain CT reveals bilateral, symmetrical calcification on anterior and medial aspects of both temporal horns

3D-volume rendering reformation from a volume CT acquisition shows, in perspective, the 2 “almond-shaped” symmetrically and mesially located calcifications

VRT re-construction CT image again shows para-sellar, bean-shaped calcification

Coronal T2 W

well-defined, symmetrical, signal-voids antero-medial to the temporal horns, precisely corresponding to the para-sellar calcification

well-defined, bilateral symmetrical, low signals noted in the antero-medial to the temporal horns, precisely corresponding to the para-sellar calcification

CORONAL IMAGES

Histopathology of punch biopsy from yellowish plaques on skin showed abundant deposition of amorphous eosinophilic material surrounding the sweat glands, capillaries and in the thickened papillary dermis

HISTOPATHOLOGY

The hyaline like material - diastase resistant and PAS positive

These findings were consistent withthe radiological finding of LP.

DDx

•EPP+Skin lesions in Erythropoietic protoporphyria(EPP) have similar appearance, the depositsare not seen around sweat glands +Increased protoporphyrin levels in erythrocytes are also seen in EPP

•Deposits in amyloidosis and xanthomas have different chemical composition although externally skin might appear similar as in LP.

•Primary cutaneous amyloidosis+Hyperpigmented papulonodular eruptions occur, especially on the shins and upper limbs that may coalesce into thickened plaques+A skin biopsy with Congo red stain helps in making the diagnosis

Xanthomatosis

Myxoedemahoarseness of voice, macroglossia, thickening of skin and chronic periorbital infiltration secondary to the deposition of mucopolysaccharides frequently develop as a result of decreased thyroid hormone

Lichen myxedematosus +small domeshaped flesh to cream coloured, firm, waxy, lichenoid papules, arranged in a linear manner particularly on the face (glabella and behind the ears) and dorsum of hands, producing a distinctive clinical appearance.

calcified gliomas located in the amygdalohippocampal region in pediatric patients but they are neither bilateral nor symmetrically distributed.

Raine syndrome, a rare autosomal recessive osteosclerotic bone dysplasia, is characterized, among other findings, by intracranial calcifications (mainly affects the basal ganglia )

Complications•Laryngeal involvement may lead to airway obstruction. Vocal cord involvement may lead to impaired speech

•Intracranial calcifications may result in seizures, behavioral changes, rage attacks, and dystonia

•The deposition of hyaline in the small bowel is reported to cause gastrointestinal bleeding

Prognosis•Lipoid proteinosis has a stable or slowly progressive course

•The presence of this disease is compatible with a normal life span unless altered by airway obstruction or fatal seizure activity

•Mortality rates in infants and adults are slightly increased because of laryngeal obstruction.

Patient Education

The parents should be educated about the risk of having affected offspring

KEY POINTS

•Bilateral symmetric amygdaloid calcifications

• Moniliform blepharosis