Amyloidosis is a collection of diseases in which proteins accumulate in one or more body parts, causing impaired organ function. The kidney, heart, nervous system, gastrointestinal tract, and skin are commonly affected. Cutaneous amyloidosis is the accumulation of amyloid protein in the wave-like projections between the two superficial layers of skin. The primary feature of cutaneous amyloidosis is a skin patch with abnormal color or texture.
What Is the Cause of Cutaneous Amyloidosis?
Mutations of the OSMR or IL31RA gene cause cutaneous amyloidosis.
OSMR gene mutation is type 1, and an IL31RA gene mutation is known as type 2. Mutations of either OSMR or IL31RA gene causes lichen and macular amyloidosis, but the cause of nodular amyloidosis is yet to be identified. The OSMR and IL31RA genes provide signals to produce subunits of interleukin receptors which in turn combine with different proteins to form OSM receptors. The interleukin receptor and OSMR are attached to a specific protein in the cell membrane in every body part. This receptor to protein attachment produces chemical signals for proper cell functioning.
The OSM receptor interacts with the oncostatin M (OSM) protein. OSM triggered Signal helps develop blood cells, cell maturation, inflammation, and self-destruction of the cells. The IL-31 receptor signals IL-31, causing inflammation and itch. Mutation of the OSMR gene decreases signals by OSM and IL-31, while mutation of the IL31RA gene weakens only IL-31 signaling.
Cutaneous amyloidosis may not show a mutation in the OSMR or IL31RA gene. The cause in these cases is unknown.
How Is Cutaneous Amyloidosis Classified?
Amyloidosis can be systemic, involving many organs, or localized, involving only one organ or system. Skin can be associated in both ways.
Systemic Amyloidosis Secondary to Cutaneous Alterations:
Reactive systemic secondary amyloidosis of certain cutaneous inflammatory conditions are seen in leprosy, cutaneous tuberculosis, psoriasis, discoid lupus erythematosus, hidradenitis suppurativa, dystrophic epidermolysis bullosa, infected burns, or other dermatoses.
Changes in the skin in systemic amyloidosis include deposition of amyloid around lymphatic vessels, bleeding with purpura, petechiae, ecchymoses, alopecia, cutis laxa, bullae, and blisters. Hemorrhages occur on the tongue or buccal mucosa. Extensive cutaneous ulceration or nail dystrophy is very rare. Macroglossia is commonly seen.
Localized Cutaneous Amyloidosis:
There are two types of localized cutaneous amyloidosis. They are:
Keratinic amyloidosis is the deposition of keratin from the basal keratinocyte. It is classified as follows:
Based on the source of lesion:
In primary keratinic amyloidosis the keratin deposition occurs first, leading to a secondary skin lesion. However, the primary form occurs secondary to persistent rubbing or scrubbing; hence primarily the lesion is also known as ‘‘friction amyloidosis’’.
The secondary keratinic amyloidosis type occurs secondary to an existing condition like inflammatory condition, basal cell carcinoma, sweat gland tumors, trichoblastoma, melanocytic nevus, actinic keratosis, seborrheic keratosis, Bowen disease, mycosis fungoides, or PUVA treatment.
Based on the type of lesion:
In macular amyloidosis, the lesions are poorly defined patches, reticulate or ‘‘rippled’’ appearance with subtle amyloid deposition. It is common in women, located at the back, trunk, or thighs.
Lichen amyloidosis usually presents as pruritic discrete hyperpigmented papules that later unite as diffuse pigmentation without bumps. There is prominent amyloid deposition. It is commonly seen in the arms, calves, back, and dorsum of the feet. Lichen amyloidosis co-exists with other skin conditions like angiolymphoid hyperplasia and eosinophilia.
Nodular amyloidosis is made of light immunoglobulin chains (AL type amyloid), but no blood disorders are found. Hence, it is described as a localized disease. When systemic involvement is present, the prognosis of the disease is poor. In case of systemic involvement, gene rearrangement studies are to be performed.
Clinically, it is presented as single or multiple waxy nodules with or without overlying atrophic epidermis and is known as masquerading a foot callus. It is located in the eyelids, noses, trunk, extremities, and genitalia. Sometimes, the amyloid deposit is seen in the blood vessels and the nerve sheaths. Rarely dystrophic calcification or bone formation is seen. It may be associated with CREST syndrome.
What Are the Variations in Cutaneous Amyloidosis?
A poikiloderma-like cutaneous syndrome - poikilodermatous skin lesions, lichenoid papules with a cutaneous amyloid deposit in pigmented and lichenoid lesions. Patients are sensitive light, short in stature, with blisters or palmoplantar keratosis.
An X-linked pattern of inheritance is also seen in cutaneous amyloidosis. It is related to amyloidosis cutis dyschromic, which is a familial type of amyloidosis that presents as reticulate hyper and hypopigmentation of the trunk and limbs.
How Is Primary Cutaneous Amyloidosis Treated?
The treatment of lichen and macular type of cutaneous amyloidosis aims to relieve itch. It includes:
A. Non-invasive Treatments:
Topical and intra-lesion steroids.
Topical dimethyl sulfoxide (DMSO).
Phototherapy (UVB or PUVA).
B. Surgical Therapy:
Excising the specific lesions.
The treatment of a nodular type of localized cutaneous amyloidosis is aimed at improving appearance. It includes:
Primary cutaneous amyloidosis may persist or relapse after treatment but is limited to the skin, and no systemic spread is seen.
What Is the Prognosis of Cutaneous Amyloidosis?
Most patients when left untreated die within one to two years after diagnosing amyloidosis due to heart or kidney failure.
Cutaneous amyloidosis is a skin disease of amyloid deposition, a complex protein structure. The exact cause of cutaneous amyloidosis is yet to be identified. It may be associated with conditions like atopic dermatitis, sarcoidosis, and psoriasis. Most cases are seen at different intervals with no family history. But when rare familial forms occur it is due to changes in the OSMR or IL31RA gene. Treatment depends on the clinical presentation of an individual including medications or surgery.
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