Black acanthosis vulvae

　　1. Etiology

　　The etiology of vulvar acanthosis nigricans is not yet clear, and it may be caused by a cell-level enhancing stimulatory factor acting on the receptors of keratinocytes and fibroblasts. Tumor products seem to be the etiology of malignant acanthosis nigricans, but insulin resistance is considered to be the cause of most acanthosis nigricans patients without malignant tumors. Insulin binds to its classic receptor to produce biological effects, and its receptor is a glycoprotein encoded by a single gene located on the short arm of chromosome 19. Insulin binds to its receptor on the cell membrane to form a complex, causing cytoplasmic dissolution. Later, this receptor can be reused or degraded in lysosomes. In this complex process, the function of the insulin receptor can be blocked by various defects, leading to insulin resistance. These defects include the lack of insulin or insulin antibodies, a decrease in the number or binding strength of classic insulin receptors, or abnormal signal transduction due to the failure to activate the tyrosine kinase receptor. Insulin resistance can also occur in insulin-like receptors, such as high concentrations of insulin that can activate the insulin-like growth factor 1 receptor and mediate epidermal cell proliferation. High concentrations of insulin can also bind to growth factor-like peptide receptors to stimulate growth, forming type A syndrome. Some patients with acanthosis nigricans have insulin receptor antibodies, indicating that acanthosis nigricans is related to various autoimmune phenomena and characteristics, and can also explain the symptoms of various type B syndromes. Most cases of malignant acanthosis nigricans are caused by the secretions of tumor products, which have insulin-like activity at the cellular receptor level. Among them, transforming growth factor (TGF-α) is structurally related to epidermal growth factor (EGF), but the antigenicity is different, which may be a factor causing acanthosis nigricans, as it has a significant mitogenic effect on keratinocytes in vitro.

　　Acanthosis nigricans may also be caused by drugs or autoimmune reactions, such as local acanthosis nigricans caused by subcutaneous injection of insulin, and there is a case of acanthosis nigricans occurring in a graft-versus-host reaction.

　　2. Pathogenesis

　　High concentrations of insulin can stimulate DNA synthesis and cell proliferation through insulin-like growth factor alpha-1 (IGF-1), and IGF-1 receptors exist in keratinocytes, ovaries, and the heart. The tumor secretions of patients with malignant acanthosis nigricans have insulin-like activity, among which transforming growth factor alpha' (IGF-α) is structurally related to epidermal growth factor (EGF). The former can promote keratinocyte mitosis through the amplifying effect of the EGF receptor, leading to significant proliferation and triggering the disease. In addition, the disease can also be triggered by other factors acting at the cellular receptor level, such as drugs (niacin, diethylstilbestrol, insulin) or autoimmune reactions. For example, subcutaneous injection of insulin can cause local acanthosis nigricans, and acanthosis nigricans can occur after immunosuppressive treatment in renal transplant patients.

　　Histopathology: mild to moderate hyperkeratosis and papillomatous tumor hyperplasia of the epidermis, irregular thickening of the prickle layer, dermal papillae presenting as finger-like upward protrusions, with mild to moderate thickening of the prickle layer in the interdigital depressions, filled with keratin. The stratum corneum on the tops of the papillae and around the epidermis becomes thinner, with mild pigmentary increase in the basal layer. Melanophages are visible in the dermis, and there is mild lymphocytic infiltration around the blood vessels.

　　Epidermal mild to moderate hyperkeratosis and papillomatous tumor hyperplasia, irregular thickening of the prickle layer, dermal papillae presenting as finger-like upward protrusions, with mild to moderate thickening of the prickle layer in the interdigital depressions, filled with keratin. The stratum corneum on the tops of the papillae and around the epidermis becomes thinner, with mild pigmentary increase in the basal layer. Melanophages are visible in the dermis, and there is mild lymphocytic infiltration around the blood vessels. Multiple skin tags may be present. Malignant acanthosis nigricans patients may have itching. The progression and prognosis vary by type. In severe cases, the vaginal mucosa may occasionally have pigmentless papillomatous lesions or hyperpigmented spots.

　　Vulvar acanthosis nigricans is often part of generalized or localized acanthosis nigricans, mainly affecting the inguinal region, upper inner thigh, pubic area, and large labia with hyperpigmented spots and velvety thickening. It may be accompanied by multiple skin tags. Generally, there is no discomfort. Malignant acanthosis nigricans patients may have itching, and the progression and prognosis vary by type.

　　The disease can be divided into 8 types, but the basic skin lesions are similar, with differences in severity, distribution range, presence of complications, and malignant tumors. The skin first shows hyperpigmentation, dryness, and roughness, then the skin lesions gradually thicken, the skin creases deepen, and there appear dense clusters of small papillomatous proliferations or a velvety appearance. Hyperpigmentation also gradually deepens, becoming gray-brown, brown-black, or black. In severe cases, the skin becomes thickened with papillomatous or warty nodules on the surface. Lesions commonly occur on the sides of the neck, nape, underarms, areolas, nipples, umbilicus, and flexural areas of the elbows and knees, with hyperkeratosis and thickening of the soles and palms. The scalp thickens with papillomatous lesions and hair loss. The eyelids and conjunctiva lose luster and may have papillomatous hyperplasia. Papillomatous hyperplasia can block the tear ducts, causing epiphora. Thicker eyelids can also block the meibomian gland orifices. The oral mucosa and tongue may also thicken and show papillomatous hyperplasia, but generally without hyperpigmentation. The nails may become brittle with striated ridges and may also thicken, and white nails may occur.

　　Type I Benign Acanthosis Nigricans

　　This is a rare genetic skin disease, inherited in an autosomal dominant manner, often with a familial genetic predisposition, showing different phenotypic penetrance. It usually manifests after birth or in early childhood, with early symptoms of unilateral skin lesions, which are epidermal nevi. Sometimes, it is accompanied by multiple melanocytic nevi. The skin lesions stop developing during adolescence and thereafter remain stable or slowly regress. In a family survey of 13 patients, one or more similar patients were found in the families of 9 individuals. Obesity is not related to the disease. Chuang et al. (1995) reported a familial acanthosis nigricans case, where the mother was a 35-year-old patient with acanthosis nigricans, and her 7-year-old son and 5-year-old daughter both had acanthosis nigricans. None of the three had eyebrows or eyelashes. The mother had no hair in the armpits and sparse hair in the pubic area. The boy had congenital heart disease and cataracts in the left eye, hence the black acanthosis nigricans in this family was associated with ectodermal dysplasia.

　　Second, specific type

　　It is not accompanied by malignant tumors, congenital hereditary diseases, or endocrine diseases, but is often accompanied by obesity. Obesity has insulin resistance, which was previously called pseudo-acanthosis nigricans. Hud (1992) reported that in a random check of 34 adult obese patients in an adult obesity clinic, 74% (25/34) of black patients had varying degrees of acanthosis nigricans, and 33% of patients with body weight over 120% to 150% of the ideal weight had acanthosis nigricans; 82% of patients with body weight over 120% to 200% of the ideal weight had acanthosis nigricans, and all 4 patients with body weight over 250% had acanthosis nigricans. In white obese individuals, only 57% (8/14) had acanthosis nigricans. The average blood insulin concentration after fasting in obese patients with acanthosis nigricans was higher than that in patients without acanthosis nigricans. When the patient's weight returns to normal, acanthosis nigricans can regress.

　　Third, endocrine type

　　It is often accompanied by endocrine diseases, especially increased secretion of the adenohypophysis and adrenal gland diseases, such as acromegaly, Addison's disease, diabetes, etc. For example, Brockow et al. (1995) reported a 12-year-old girl who developed acanthosis nigricans due to elevated serum insulin.

　　1. Insulin-resistant type A syndrome:

　　Type A syndrome is more common in young women, with symptoms of masculinization or rapid growth, also known as HAIR-acanthosis nigricans syndrome, i.e., hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans. It has a familial tendency, often onset in infancy, and some may have hirsutism and polycystic ovaries, acromegaly, clitoral hypertrophy, and muscle cramps. The skin lesions of acanthosis nigricans are often diffuse, the skin lesions progress rapidly in adulthood, and the level of testosterone in the blood is high.

　　2. Insulin-resistant type B syndrome:

　　The onset is later, with an average age of 39 years. The symptoms of acanthosis nigricans can vary in severity and may be associated with systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, vitiligo, and Hashimoto's thyroiditis, but usually only laboratory evidence of autoimmune disease is present, such as high-titer anti-DNA antibodies and leukopenia.

　　Fourth, malignant type

　　Induced by malignant tumors, it is different from those with combined neoplasms and acanthosis nigricans, where the latter has an earlier onset age, often remains static without expansion. Malignant acanthosis nigricans has three skin signs common to other visceral malignant tumors, namely Lesser-Trelat sign, papillomatosis of the skin of the natural redness, and hyperkeratosis of the palms and soles. It is believed that acanthosis nigricans and these three skin signs are a similar response to a hereditary or malignant-related factor. These three signs often appear before acanthosis nigricans and are rarely associated with other skin lesions of visceral tumors, such as hypertrophic periostosis, paraneoplastic pemphigus (paraneoplastic pemphigus), hypertrichosis, and rapid, severe, and extensive skin lesions with prominent pigmentation, not limited to thickened skin lesions. Typical skin lesions are also found at the mucocutaneous junctions, and there are papillomatous hyperplasia around the eyes and lips, with brittle nails showing longitudinal ridges. Itching or irritation is often present at the site of skin lesions.

　　In a recent statistical study, dyskeratosis congenita preceded the tumor in 51 of 74 cases, accounting for 69% (Gross). Curth believes that the latent period of the tumor is 10 to 15 years, dyskeratosis congenita can be associated with one or more tumors. To confirm which tumor is related to dyskeratosis congenita, it is necessary to conduct a clinical investigation to understand the relationship between dyskeratosis congenita and tumors in the pathogenesis, and to decide whether the skin lesions regress after the tumor is removed. Curth pointed out in a retrospective analysis that 92% of 177 cases of malignant dyskeratosis congenita were abdominal tumors, among which 69% were gastric cancer, others were lung cancer, liver cancer, cervical cancer, breast cancer, and ovarian cancer, etc., and believed that most of the intrinsic tumors were adenocarcinomas.

　　5. Acral dyskeratosis congenita

　　It is more common in black people, and it has also been found in China recently. The author has seen one case, where the skin lesions are limited to the dorsal aspect of the hands and feet, presenting with velvety hyperkeratosis, brownish in color, which is a variant of dyskeratosis congenita. The overall health condition is good, without other complications.

　　6. Unilateral dyskeratosis congenita

　　This type can be the earliest manifestation of bilateral benign dyskeratosis congenita, but it can also persist as unilateral distribution, possibly as nevus-like damage, and some people also call it nevus-like dyskeratosis congenita. It is an irregular autosomal dominant inheritance, which can occur at birth, during childhood, or adolescence. The skin lesions gradually expand over a certain period of time and then remain stable or regress.

　　7. Drug-induced dyskeratosis congenita

　　This type is very rare, and possible causative drugs include corticosteroids, niacin, diethylstilbestrol, insulin, pituitary extracts, triazolopyrimidine, methandienone, oral contraceptives, and fusidic acid (sphingosine acid) may also induce the disease. Local application of fusidic acid (sphingosine acid) can cause dyskeratosis congenita lesions.

　　8. Mixed dyskeratosis congenita

　　The patient has two types of dyskeratosis congenita lesions simultaneously. Generally, malignant dyskeratosis congenita often appears in patients with other types of dyskeratosis congenita, such as the case reported by Curth of a child with unilateral dyskeratosis congenita, who later developed bilateral lesions and abdominal malignant tumors. In addition, there is the Hirschowitz syndrome, which was proposed by Hirschlowitz in 1989. This condition has extensive dyskeratosis congenita, combined with childhood familial complete sensorineural deafness, progressive peripheral sensory demyelination, and gastrointestinal diseases, fat malnutrition, and dyskeratosis congenita was first described by Law Vence in 1946, and reported by Slip in 1959, hence also known as Lawvence-Seip syndrome. This syndrome has both genetic and acquired forms, and dyskeratosis congenita can be associated with generalized complete subcutaneous fat atrophy, with severe insulin resistance.

　　Other syndromes associated with melanotic acanthosis include Leprosy dwarfism syndrome, hepatolenticular degeneration, Bloom syndrome, Rud syndrome, pituitary alkaline cell增多症, other familial pineal gland hyperplasia of pituitary tumors, adrenal cortical hyperplasia and diabetes (R-M syndrome), and some diseases with autoantibodies including insulin receptor antibodies (such as lupoid hepatitis, liver cirrhosis, systemic lupus erythematosus, dermatomyositis, and systemic sclerosis).

　　1. Precautions:Differential diagnosis of vulvar melanotic acanthosis with vulvar follicular keratosis. Vulvar follicular keratosis has basic damage as follicular papules, which fuse into proliferative plaques in the axilla, inguinal folds, and other creases, with exudation and foul odor. Histopathological examination shows: dyskeratosis, spherules, acrosome granules, basal layer fissures, etc., which can be differentiated from melanotic acanthosis. It is important to distinguish malignant melanotic acanthosis from other types of melanotic acanthosis and to find visceral malignant tumors according to the characteristics of the malignant melanotic acanthosis skin lesions, so as to treat early.

　　Melanotic acanthosis caused by drugs, possible causative drugs include corticosteroids, niacin, diethylstilbestrol, insulin, pituitary extracts, tricyclic phenylamide, methyltestosterone, oral contraceptives, and fusidic acid (sphingosine acid) may also induce, and local application of fusidic acid (sphingosine acid) may cause skin damage of melanotic acanthosis.

　　2. Epidemiology:Melanotic acanthosis can occur at any age and is relatively rare.

　　3. Prognosis:About 50% of patients who develop the disease after middle age have cancer.

　　4. Complications:In severe cases, the vaginal mucosa may occasionally be accompanied by pigmentless papillary hyperplastic lesions or pigmented spots.

　　Vulvar melanotic acanthosis is a rare vulvar skin disease that commonly occurs in the vulvar creases, characterized by vulvar skin pigmentation, papillary hyperplasia, hyperkeratosis, and symmetrical distribution. According to the characteristic velvety thickening, pigmentation, and special distribution of the skin in this disease, it is easy to diagnose. Histopathological examination can confirm the diagnosis.

　　1. Laboratory examination:Blood biochemical testing, islet cell function testing, and sex hormone level testing.

　　2. Other auxiliary examinations:Histopathological examination.

　　I. Dietetic recipe for vulvar melanotic acanthosis

　　1. Seaweed and Mung Bean Porridge

　　Seaweed 30 grams, mung bean 30 grams, sugar to taste, glutinous rice 100 grams.

　　Preparation method: first wash the kelp and cut it into pieces, soak mung beans for half a day, wash the glutinous rice clean, and cook them together as congee. Add sugar for seasoning when it is cooked.}}

　　Usage: Take twice a day in the morning and evening, and it is recommended to continue for 7 to 10 days.

　　Its efficacy is to clear heat and detoxify, and promote diuresis and heat expulsion. It is suitable for vulvar itching.

　　2. Coix Seed and Red Date Congee: 30g coix seed, 10 red dates, 50g rice.

　　Wash and cook together as congee for consumption. It has the effect of clearing heat, invigorating the spleen, and stopping itching.

　　3. He Shou Wu Mulberry Sesame Congee: 30g He Shou Wu, 10g mulberry fruit, 10g black sesame, 50g rice.

　　Wash and cook together as congee for consumption. It has the effect of nourishing blood, moistening the yin, and stopping itching.

　　4. Steamed pork liver: 60g pork liver, 30g herba serissae.

　　Cut the pork liver and herba serissae into small pieces, mix well, place in a covered bowl, and steam in a steamer for 30 minutes. Take all at once. It has the effect of clearing heat and removing dampness.

　　Second, what not to eat for vulvar acanthosis nigricans:

　　Avoid seafood and irritant, sensitizing foods when itching is severe.

　　First, precautions before the treatment of vulvar acanthosis nigricans:

　　1. Adjust the diet structure, appropriately reduce weight;

　　2. Actively treat internal medical diseases; remove the causative drug for those caused by drugs; follow up well.

　　Second, traditional Chinese medical treatment methods for vulvar acanthosis nigricans

　　There are currently no very effective treatment methods or drugs.

　　Third, Western medical treatment methods for vulvar acanthosis nigricans

　　For etiological treatment, if malignant acanthosis nigricans is suspected, early examination and excision of malignant tumors should be performed as soon as possible; for obesity-related acanthosis nigricans, weight loss and correction of obesity can naturally alleviate the skin lesions; for symptomatic acanthosis nigricans, active treatment of other diseases such as hyperinsulinemia and androgen excess should be carried out; for those caused by drugs, the rash will regress after the causative drug is discontinued.

　　For the treatment of this disease, supplementation with fish oil can improve the condition, and the use of topical vitamin A acid preparations can also have a certain effect. Topical application of a moderate concentration of keratolytic agents, such as 10% sulfur coal tar ointment, can also be effective.

　　If malignant acanthosis nigricans is suspected, necessary examinations should be conducted as soon as possible, and the lesion should be excised as early as possible. The skin lesions can regress. Obese individuals should reduce weight, and the skin lesions can naturally diminish. For drug-induced acanthosis nigricans, the causative drug should be removed, and for those with associated syndromes, active treatment of other diseases should be carried out.