A Review of Fabry Disease

Brandon Chan; David N. Adam, MD, FRCPC, DABD

Disclosures

Skin Therapy Letter. 2018;23(2):4-6. 

In This Article

Other Signs and Symptoms

Pain

The incidence of pain in FD has been reported in 81.4% of male patients and 65.3% of female patients. The average age of onset of pain has been found to be 14.[8] years for males and 19.8 years for females.[6] Pain is possibly caused by the deposition of GL3 in the dorsal root ganglia and sympathetic ganglia, or by small fiber neuropathy. Generally, the pain is either chronic or episodic. Episodic pain in FD, termed "Fabry crises," typically begins in the extremities and radiates proximally, and may be triggered by exercise, illness, temperature changes, or other physical and emotional stresses. This neuropathic pain is also associated with a lack of temperature perception.[7]

Sweating Abnormalities

Hypohidrosis is prevalent in FD patients, with reported incidence of 53% in males and 28% in females. Anhidrosis has been observed in 25% of males and 4% of females. Hyperhidrosis occurs less frequently, with 6% of males and 12.6% of females reporting this symptom.[8]

Cornea Verticillata

Cornea verticillata are whorl-like corneal opacities, resulting from changes in the subepithelial layers of the cornea.[9] It is the most common ocular manifestation of FD, observed in 76.9% of females and 73.1% of males. Other less common ocular manifestations include vessel tortuosity and Fabry cataracts. Cornea verticillata may also be pathognomonic for FD, as its differential diagnosis only includes specific medications, such as amiodarone and aminoquinolines. However, it does not have predictive value with regards to disease severity.[10]

Angiokeratoma

Angiokeratoma (AGK) is the most common cutaneous manifestation of FD, and has been reported in 66% of males and 36% of females.[8] In FD, AGKs appear as non-blanching, red to blue-black lesions ranging from 1 to 5 mm in diameter.[11]

The age of onset for AGKs is typically 5–10 years in males.[12] The distribution of AGK in males with FD is mainly on the penis, scrotum, inner thighs, lower back, buttocks, and the umbilicus. In females, AGKs are mainly found on the trunk and limbs.[11] While patients with FD generally describe an increasing number of cutaneous lesions over time, no correlation has been found between age and the extent or number of lesions.[8] It is possible older patients are more observant of their skin and, therefore, report more AGKs.

The distribution of AGKs in FD differs from AGK in other diseases. Angiokeratoma of Fordyce usually appears after age 30 and is found on the genitals, angiokeratoma of Mibelli generally presents on the extensor surfaces of hands and feet, and angiokeratoma circumscriptum naeviformis is concentrated on the trunk and extremities.,[1,13] Idiopathic AGK is also possible without any specific localization.[13]

Diffuse AGK has also been observed in other lysosomal storage diseases, including fucosidosis, sialidosis, GM1 gangliosidosis, galactosialidosis, beta-mannosidosis, Schindler disease type II, and aspartylglucosaminuria.,[1,11]

AGK histology reveals a vascular proliferation inside the papillary dermis. The overlying epidermis is acanthotic and orthokeratotic. The vascular channels are occasionally plugged with erythrocytes. Dermoscopy of AGK shows red to bluish black vascular lacunaewith clear borders. Occasionally, overlying yellow keratotic areas are also observed.[11]

Currently, it is unclear whether AGK can be used as a biomarker for disease progression or as a measure of efficacy of enzyme replacement therapy.[14] However, when stratified by age, male and female FD patients with cutaneous vascular lesions (angiokeratomas and telangiectasiae) were shown to more likely have major organ involvement.[8]

Telangiectasia

Telangiectasia is reported to be the second most common cutaneous symptom of FD.[8] In FD, telangiectasias are found on the face, lips, oral mucosa, and photodamaged areas such as the V of the neck.[11]

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