Found To Develop Around Regions Of Armpits â€Myassignmenthelp.Com

Question: Discuss About The Found To Develop Around Regions Of Armpits? Answer: Introducation Acanthosis Nigricans is defined as a disorder of the skin characterized by hyperpigmentation (darkening) and hyperkeratosis (thickening) in certain areas of the body. Usually it is found to develop around regions of armpits, groins and neck. Often it is misinterpreted by patients as decolouration of the skin, which eventually will not get washed away even after vigorous scrubbing. In the past the condition was mostly associated with internal malignancy and other genetic disorders. Recent studies have shown that although Acanthosis Nigricans is not in itself a medical condition but is a potent biomarker of less debilitating disorders like obesity and insulin resistance. Acanthosis Nigricans is a reliable indicator of hyperinsulinemia in obese patients and the severity of the condition largely depends on the magnitude of hyperinsulinemia and obesity (Sinha Schwartz, 2007). Hyperinsulinemia leading to this condition is thought to be caused mainly due to receptor and post-receptor defec ts in the patient. Although the exact incidence of the disease is still unknown it has been closely associated with obesity and much less associated with malignancy. The most frequent association with malignancy was found to be with gastrointestinal tract cancer and gastric cancers. Studies report that Acanthosis Nigricans is much more common in people with dark skin pigmentation showing a clear indication of its association with race or ethnicity (Puri, 2011). However, the difference in incidence due to racial makeup cannot be attributed solely to direct causal factors such as obesity or diabetes, a yet to be discovered genetic predisposition may be playing an important role for such discrepancies. It has been shown that the condition is prevalent in more or less equal proportion in both men and women and hence has no sex prediction. Age is also not a significant determinant of the condition as it may happen to occur at any age. However, malignancy related Acanthosis mostly occurs in elderly. Neck is the most common region of the body that is affected by the condition; other commonly affected regions include lips, eyelids, mucosal surfaces and flexural regions of groin, knees and elbows (Miller Rapini, 2011). Usually Acanthosis Nigricans is a symptomatic, however, patient often report unpleasant sensation over the affected region causing an urge to scratch. Pathophysiology In Acanthosis Nigricans the epidermal keratinocytes are stimulated and the fibroblasts on the dermal layer proliferate more than usual resulting in hyperpigmented plaques mostly in the intertriginous surfaces of the neck. Factors that affect such proliferation and stimulation may have a direct effect on the severity of the condition. The exact underlying cellular pathogenesis of Acanthosis is yet to be discovered, however, it has been postulated that the entire pathogenesis is related to endocrine or tumour producing growth factors that act on the insulin like receptors located on the epidermal cells of the skin (Krawczyk, Myka?aCie?la Ko?odziejJasku?a, 2009). Epidermal growth factors and transforming growth factors, fibroblast growth factors play a pivotal role in Acanthosis related to tumour, inciting epidermal cell propagation. Transforming growth factor alpha and epidermal growth factor both are found in high concentration in gastric adenocarcinoma cells and simultaneously epide rmal growth factor receptors are expressed in Acanthosis affected skin cells (Kong et al., 2007). On the other hand obesity related Acanthosis involves the action of insulin like growth factors and the hormone insulin itself on their respective receptors on the target cells. It is most commonly associated with insulin resistance disorders such as type 2 diabetes, obesity and polycystic ovary syndrome. Further, obesity and diabetes are often comorbid conditions and hyperinsulinemia causes the high affinity receptors, Insulin-like growth factors-1 receptors to be activated both by insulin and insulin-like growth factor-1 (Wang et al., 2013). This results in higher cell growth and proliferation. Certain factors indicate that insulin dependent activation of IGF-1 receptors can independently promote the development of Acanthosis. Fibroblasts and keratinocyte express the IGF-1 receptors, insulin has the ability to cross the dermoepithelial junction and activate the above mentioned receptors and lastly it has been proven that severity of Acanthosis depends directly on the fasting insuli n levels of the patient. Hyperinsulinemia may also indirectly cause Acanthosis. IGF binding proteins, which regulate the levels of IGF-1 in circulation, are decreased in patients with hyperinsulinemia resulting in increased concentrations of IGF-1, which in turn promotes cell growth and proliferation (Phiske, 2014). The post receptor intracellular pathways related to Acanthosis are likely to converge at some point, although the exact interrelationship is not clearly elucidated yet. Adverse effect of certain medications that induce hyperinsulinemia may indirectly promote Acanthosis (Buzsi, Spi Jermendy, 2011). Lesions may retreat on discontinuation of medication or by administering the optimal dosage. Certain types of Acanthosis may develop due to autosomal genetic defects, manifestation of which starts at early childhood and may stabilize at an adult age. In autoimmune disease like systemic lupus erythematosus, which is characterized by production of antibodies against insulin receptors may eventually result in the development of Acanthosis. Clinical Features: Histology Several physical clinical features can be characterized with Acanthosis Nigricans. The affected regions are characterized by symmetrical, hyperpigmented, velvety plagues. Skin tags are often associated with such plagues which are known as Acrochordons. (Kapoor, 2010) Lesions are also found in some cases. Mucous membranes of different parts of the body can also be affected by the condition such as oral and nasal cavity and oesophagus. Lesions of malignant and benign Acanthosis are clinically non distinguishable and hence diagnosis is difficult. The most common histological feature of Acanthosis is hyperkeratosis which is found all patients with the condition. Hyperkeratosis is the clinical term that implies over thickening of the outer layer of the skin, stratum corneum. In hyperkeratosis the spinous and granular cell layers undergo granular and vacuolar degeneration. It is characterised by clear spaces of variable size around the nucleus of the upper epidermal cells under the microscope. The dark couloration in Acanthosis is due to this hyperkeratosis instead of the mind increase in melanin pigmentation. Infiltration of lymphocytes, plasma cells or neutrophils maybe present in certain cases. Horn pseudocysts are also found which is characterized by numerous basaloid epidermal cells extending from the epidermis layer to the dermis and may passess branched or interweaving patterns. There are an increased number of keratohyaline granules on the granular cell layer (Hafner Vogt, 2008). Often the upper epidermis is infiltrated with inflammatory molecules and increased numbers of mitoses are also observed. Keratinocytes may be found to fall apart due to the lack of keratin filaments that provides strength to the keratinocyte cells and bullae formation may be observed due to separation of keratinocytes. Papillomatosis is the second most common histological or microscopic feature of Acanthosis. Abnormal keratinocyte differentionation and maturation are the most significant clinical features of papillomatosis. Keratin16 and Keratin 67 expression are often augmented resulting in increased transition cell layer and increased lamellar granules in the stratum granulosum. Epidermolytic hyperkeratosis is sometimes found with lesions. The epidermal hyperplasis can be classified according to the thickening of the epidermis. Flat hyperplasia occurs when the entire region undergoes moderate thickening, proriasiform occurs when epidermal layers are extended and papillomatous hyperplasia is characterised by viral warts that project upwards. Colloidal iron tissue staining shows infiltration of glycosaminoglycans like hyaluronic acid, more often in patients with gonadal diseases. Gross Clinical Features As mentioned earlier Acanthosis Nigricans has characteristic clinical features of dark, coarse and thickened sin with a velvety texture. In the early stages of the condition grey-brown/black pigmentation is observed with marked dryness and roughness that is progressively thickened. Numerous small papillomatous elevations maybe found that provides it the velvety texture. As the disease progresses the thickening of the skin lines increase and surface becomes mammilated and wrinkled producing warty excrescences (Brickman, Huang, Silverman Metzger, 2010). Although other clinical symptoms are absent, patients often report feeling of itching on and around the affected regions. The leisions of Acanthosis are distributed symmetrically and the most common in back and sides of neck, axillae, groin and ante cubital and popliteal areas. In children the most coomon area affected is neck as compared to axillae. Less common areas that are affected include external genetalia, umbilicus, hand joints , inner aspects of thighs and also the anus. In severe conditions the diseases might spread to uncommon regions like lips, areola, conjunctive and oral mucous membrane. There are several other conditions that have similar symptoms to those of Acanthosis Nigricans. An approach of differential diagnoses is essential to distinguish between the related disorders to obtain a comprehensive idea about the condition and design appropriate therapeutic interventions. Some of the related conditions include Epidermal Naevus, Dowling-Degos disease, Confluent and Reticulated Papillomatosis Suborrhoeic keratosis and Mycosis fungoides. Epidermal Neavus is usually found in children in regions of neck, torso and extremities, which are atypical in case of Acanthosis generally located in flexural and intertriginous regions. Further lesions are linear in Epidermal Neavus. In Dowling-Degos disease lesions are reticulated in the flexural areas. The most distinguishing feature is lesions are not velvety in texture and do not appear thickened as in case of Acanthosis. Lesions may also be found on the hands and feet of the patient. Confluent and Reticulated Papillomatosis is characterized by lesion on the chest and the back, instead of Flexural areas as in case of Acanthosis. Red/ brown papules are observed having a central confluence and peripheral reticular pattern. Suborrhoeic keratosis usually prevalent in adults, show few pigmented papules on the face or chest or back region, and the lesions are mostly small; rarely plaque like lesions have been reported. In Mycosis fungoides long standing lesions or plaques are found which are generally not velvety or pigmented in nature. However, in some cases this condition may mimic Acanthosis Nigricans (Phiske, 2014). Treatment and Management Acanthosis Nigricans treatment may be directed in differently in different patients depending upon the pathophysiology and the other specific factors unique to the patient. Treat can be directed towards curing the immediate symptoms of the condition requiring coordinated efforts of professionls from different fields like dermatologists, endocrinologist, paediatricians, dietitians and oncologists. The first line of tropical treatment to be considered is retinoids, which are epidermopoeitic in nature and reduce the replacement time of stratum corneum. It may reduce hyperkeratosis and reverse the disease symptoms. Retinoids also affects cell growth and differentiation. Ammonium lactate that acts as a peeling agent that disintegrates the desmososmes may also be effective in reducing hyperkeratosis (Romo Benavides, 2008). Trichloroacetic acid acts as a epidermis destructing agent and initiates subsequent repair of the tissue. It causes coagulation of skin proteins leading to necrosis and epidermal destruction. Following epidermal disintegration an inflammatory reaction is initiated that leads to re-epithelialization and replaces smooth skin. Calcipotriol is another effective drug that inhibits proliferation and differentiation of keratinocytes reducing the clinical symptoms (Guran, Turan, Akcay Bereket, 2008). Another line of treatment may be directed towards managing the underlying cause of the condition. It may include hormone replacement therapies, discontinuation of certain Acanthosis causing drugs or administering drugs that can help reduce insulin resistance in the patient. By controlling hyperinsulinemia, Acanthosis may stop progressing, however, pigmentary skin changes may persist, which will require further medication to revert back to normal conditions. For individuals with malignancy, managing the prognosis of cancer may alleviate Acanthosis symptoms. Anti-cancer drugs, radiation therapy or surgical removal of the tumour, depending upon the severity and stage of malignancy is recommended for such patients. For patients with genetic predisposition leading to Acanthosis, genetic counselling may provide some degree of benefit. As obesity and diabetes are the most common comorbidities of Acanthosis, it is suggested that the patient remain under strict diet control and monitor his/her insulin levels in a regular basis to keep Acanthosis symptoms in control. Supportive counselling may be effective to provide adequate knowledge regarding the significance of diet and exercise and modifications in lifestyle. Obesity and weight management is indispensible in patients with Acanthosis. References Brickman, W. J., Huang, J., Silverman, B. L., Metzger, B. E. (2010). Acanthosis nigricans identifies youth at high risk for metabolic abnormalities.The Journal of pediatrics,156(1), 87-92. Buzsi, K., Spi, Z., Jermendy, G. (2011). Acanthosis nigricans as a local cutaneous side effect of repeated human insulin injections.Diabetes research and clinical practice,94(2), e34-e36. Guran, T., Turan, S., Akcay, T., Bereket, A. (2008). Significance of acanthosis nigricans in childhood obesity.Journal of paediatrics and child health,44(6), 338-341. Hafner, C., Vogt, T. (2008). Seborrheic keratosis.JDDG: Journal der Deutschen Dermatologischen Gesellschaft,6(8), 664-677. Kapoor, S. (2010). Diagnosis and treatment of acanthosis nigricans.Skinmed,8(3), 161-164. Kong, A. S., Williams, R. L., Smith, M., Sussman, A. L., Skipper, B., Hsi, A. C., Rhyne, R. L. (2007). Acanthosis nigricans and diabetes risk factors: prevalence in young persons seen in southwestern US primary care practices.The Annals of Family Medicine,5(3), 202-208. Krawczyk, M., Myka?aCie?la, J., Ko?odziejJasku?a, A. (2009). Acanthosis nigricans as a para neoplastic syndrome.Polskie Archiwum Medycyny Wewn?trznej,119(3), 180-183. Miller, J. H., Rapini, R. P. (2011). Acanthosis nigricans.emedicine. medscape. com/article/1084257-overview. Phiske, M. M. (2014). An approach to acanthosis nigricans.Indian dermatology online journal,5(3), 239. Puri, N. (2011). A study of pathogenesis of acanthosis nigricans and its clinical implications.Indian journal of dermatology,56(6), 678. Romo, A., Benavides, S. (2008). Treatment Options in Insulin Resistance ObesityRelated Acanthosis Nigricans.Annals of Pharmacotherapy,42(7-8), 1090-1094. Sinha, S., Schwartz, R. A. (2007). Juvenile acanthosis nigricans.Journal of the American Academy of Dermatology,57(3), 502-508. Wang, C. H., Lin, W. D., Bau, D. T., Chou, I. C., Tsai, C. H., Tsai, F. J. (2013). Appearance of acanthosis nigricans may precede obesity: an involvement of the insulin/IGF receptor signaling pathway.BioMedicine,3(2), 82-87.