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Acanthosis nigricans is a skin disorder where the skin becomes brown to black, thick and velvety particularly at the body folds and creases like the forehead, armpits, groin and neck. This discoloration and thickening of the skin is most commonly associated with obesity. Acanthosis nigricans is more common in darker skinned people and only occurs in less than 1% of the Caucasian population. However, it affects about 20% of overweight children thereby indicating the strong association with obesity. Although rare, it is also linked to stomach cancer irrespective of the race of the cancer patient.
What causes acanthosis nigricans?
Causes and Risks of Acanthosis Nigricans
Acanthosis nigricans is commonly caused by factors that trigger the proliferation of skin cells like the epidermal keratinocyte and dermal fibroblast. The most common cause of acanthosis nigricans is any condition which leads to elevated insulin levels like type 2 diabetes mellitus and obesity. The excessive blood insulin triggers insulin growth factor (IGF) which in turn causes proliferation of these skin cells. The rapid proliferation leads to the characteristic skin changes seen in acanathosis nigricans. Insulin injections used by diabetics is also known to activate the IGF receptors thereby accounting for the skin discoloration and thickening in insulin-dependent diabetics.
There are other possible mediators of this skin cell proliferation like tyrosine kinase receptors ( epidermal growth factor receptor or fibroblast growth factor receptor). There appears to be a genetic component as well with familial cases not associated with other syndromes are linked to FGFR mutations. In cancer, the skin cell proliferation is believed to be due to some as yet unknown substances secreted by the tumor cells.
Acanthosis nigrican may also be associated with :
- Endocrine disorders like Addison disease, hypothyroidism, hyperthyroidism, polycystic ovarian syndrome (PCOS) , Cushing disease.
- Medications like oral contraceptives, corticosteroids and niacinamide.
- Renal transplants.
- Malignancy (cancer) like gastric cancer.
Some insulin resistance syndromes like leprechaunism, Rabson-Mendenhall syndrome, Berardinelli-Seip syndrome and Dunnigan syndrome are more prone to develop acanthosis nigricans. These conditions, however, are rare compared to the diseases mentioned above.
What are the symptoms of acanthosis nigricans?
Symptoms of Acanthosis Nigricans
The hyperpigmented (dark pigmeneted), velvety thick skin in the folds and creases like axilla, groin and back of the neck are the characteristic features of acanthosis nigricans. Sometimes other body parts like lips, palms and soles are also affected. The inner lining (mucous membranes) of the oral (mouth), laryngeal (throat) and nasal (nose) cavities may also be affected but this is rare. Nail changes like hyperkeratosis and leukonychia have also been reported in some patients.
Picture of acanthosis nigricans
Image from Dermatology Atlas (www.atlasdermatologico.com.br), Samuel Freire da Silva, M.D.
Sometimes these skin lesions are associated with skin tags called acrochordons which occur in and around the dark thick patches of skin. The benign or malignant nature cannot be ascertained only on clinical examination of the lesion and further testing may be warranted. In majority of acanthosis nigricans cases the progression is slow taking months to years to develop. The skin patches rarely itch but may initially be mistaken for other skin diseases.
How is acanthosis nigricans diagnosed?
Diagnosis of Acanthosis Nigricans
- Insulin resistance screening by measuring insulin levels in blood.
- Diabetes screening by measuring glycosylated hemoglobin level or glucose tolerance test.
- Basic workup to screen for underlying malignancy where primary malignancy is suspected.
- Skin biopsy to confirm diagnosis if clinical diagnosis is not clear. On histological examination the findings will be – hyperkeratosis, papillomatosis with minimal / no acanthosis or pigmentation.
How is acanthosis nigrican treated?
Treatment of Acanthosis Nigricans
There is no treatment of choice for acanthosis nigricans. The underlying condition needs to be treated or modified.
- Drug induced acanthosis nigricans should be managed by withdrawing the inciting agent. Instead of nicotinic acid, Acipimox can be used.
- Topical medications such as topical tretinion 0.05% and ammonium lactate 12 % are a keratolytic agents used in the treatment of acanthosis nigricans.
- Oral medication such as octreotide helps with insulin resistant patient if taken for about 6 months. Some other oral agents useful for the treatment of acanthosis nigricans are etretinate, isotretinion and metformin (antidiabetic drug).
- In chronic cases where the skin lesions are widespread and causing functional or emotional disturbances, it can be treated with dermabrasion and laser therapy.
- Surgical removal is indicated for acanthosis nigricans in malignant cases.
- Cyproheptadine maybe useful in malignant acanthosis nigricans.
- Psoralen plus UVA (PUVA) treats the lesion symptomatically.
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