Chapter 36 Disturbances of Pigmentation

1. Chapter 36Disturbances of Pigmentation JoAnne M. LaRow. D.O.

2. Melanin = primary pigment producing brown coloration • Tyrosine – tyrosinase –melanin- this occurs in the melanosomes of melanocytes • Then the melanosomes are transferred from the melanocyte to a group of keratinocytes called the epidermal melanin unit • Variations in skin color is related to the number of melanosomes, the degree of melanization, and the distribution of the epidermal melanin unit

3. Pigmentary Demarcation Lines • Can be divided into five categories: • Group A- lines along the outer upper arms with variable extension across the chest • Group B-lines along the posteromedial aspect of the lower limb • Group C-Paired median or paramedian lines on the chest, with midline abdominal extension • Group D-medial, over the spine • Group E-bilaterally symmetrical, obliquely oriented, hypopigmented macules on the chest

4. Pigmentary Demarcation Lines • More than 70% of blacks have one or more lines • These are much less common in whites • Type B lines often appear for the first time during pregnancy

5. Normal Pigmentation • Normal skin pigmentation is influenced by: -the degree of vascularity -the amount & location of melanin -the presence of carotene -the thickness of the horny layer

6. Melanin Production • The amount produced is dependent on: -genetics -the amount and the wavelengths of ultraviolet light received -the amount of melanocyte-stimulating hormone(MSH) secreted - the effect of melanoccytestimulatingg chemicals like furocoumarins (psoralens)

7. Hemosiderin Hyperpigmnetation • Pigmentation due to deposits of hemosiderin occurs in: -purpura -hemochromatosis -hemorrhagic diseases -stasis ulcers ** difficult to distinguish from postinflammatory dermal melanosis clinically

8. Postinflammatory Hyperpigmentation • Any inflammatory condition can cause either hypopigmentation or hyperpigmentation • Also may be a complication of chemical peels, dermabrasion, laser therapy, or liposuction • Histologically, there is melanin in the upper dermis and around upper dermal vessels, located primarily in macrophages (melanophages)

9. Postinflammatory hyperpigmenation • Postinflammatory hyperpigmentation following resolution of lymphocytoma cutis on the cheek of a black child

10. Industrial Hyperpigmentation • Occurs in coal miners, anthracene workers, pitch workers, etc • Pigmentation of the face may occur from the incorporation in cosmetics of derivatives of coal tar, petrolatum, or picric acid, mercury, lead, bismuth, or furocoumarins (psoralens)

11. Systemic Diseases • Syphilis, malaria, pellagra, and diabetes • Addison’s disease- diffuse melanosis pronounced in the axillae and palmar creases, and nipples and genitals, and buccal mucosa • Diabetes produces diffuse bronzing of the skin • ** patients with virilizing adrenal tumors usually develop hyperpigmentation and hypertrichosis

12. Nelson’s syndrome (a pituitary MSH-producing tumor) Pheochromocytoma Hemochromatosis Amyloidosis Scurvy Pregnancy Menopause Porphyria cutanea tarda Vitamin B12 deficiency Kwashiorkor Vitamin A deficiency Primary biliary cirrhosis (triad= hyperpigmentation, pruritis, xanthomas) Systemic Diseases

13. Characterized by: Gray-brown mucocutaneous hyperpigmentation Diabetes mellitus hepatomegaly Usually are present: Cirrhoisis Hypogonadism Liver cirrhosis Hemochromatosis

14. Skin pigmentaion is usually generalized But, more pronounced on face, extensor aspect of the forearms, backs of the hands, and the geniocrural area Iron is deposited in the skin Iron is present as granules around blood vessels and sweat glands and within macrophages The actual pigmentation is caused by increased basal-layer melanin Mucous memebranes are pigmented in up to 20% of patients Koilonychia is present in 50% Localized ichthyosis in 40% Alopecia is common Hemochromatosis

15. Occurs mostly in men in their sixties Women who have genetic hemochromatosis can have full phenotypic expression Extremely rare in the young Neonatal hemochromatosis has been associated with intrauterine infections ie cytomegalovirus Adults with hemochromatosis are susceptible to Yersinia enterocolitica Dx: Elevated plasma iron and IBP High serum ferritin without an obvious cause should prompt investigation for both hemochromatosis and PCT Etiology is either an inborn error of metabolism or excessive number of blood transfusions AR gene for heredity hemochromatosis is linked to the HLA-A locus on chromosome 6p Hemochromatosis

16. Phlebotomy until satisfactory iron levels are found Extracorporeal chelation has also been used successfully Associated DM requires medical tx Long-term complications are cirrhosis and then hepatomas Hemochromatosis-tx

17. Brown patches, sharply demarcated, typically on the malar prominences and forehead The three clinical patterns are: centrofacial, malar, mandibular Increased pigment may simultaneously occur around the nipples and external genitalia Tends to affect the darker-complected It may also be found on the forearms Occurs at pregnancy and at menopause It may also be seen in ovarian disorders and other endocrine disorders Most frequently 90% of the time seen in women, 10% in men Melasma

18. Strong association with the use of birth control pills or dilantin Discontinuing the contraceptives rarely clears the pigmentation, and it may last for years after discontinuing them. Melasma of pregnancy usually clears within a few months of delivery Tx- avoid sunlight, and a complete sun block with broad-spectrum UVA coverage should be used daily Kligman’s formula (Triluma) > then 4% hydroquinone may be needed Side effects of this is ochronosis and satellite pigmentation Jessner’s solution, glycolic acid peels,azelaic acid, kojic acid, and cystamine and buthionine sulfoximine are other options Melasma

19. Melasma

20. Melasma

21. Melasma

22. AKA acropigmentation A progressive pigmentary disorder first described in a Japanese infant Characterized by diffuse black pigmentation on the dorsum of all the fingers and toes Pigmentation became progressively more widespread and more pigmented By age 4 or 5 the perineum, extremities, and areas of the head and neck were involved Epileptiform seizures occurred History revealed consanguinity Acromelanosis Progressiva

23. Acropigmentation of Dohi Found to affect individuals from Europe, India, Caribbean First described in Japan in 12 patients AKA dyschromatosis symmetrica hereditaria or symmetrical dyschromatosis of the extremities Patients develop progressive pigmented & depigmented macules Often mixed in is a reticulate pattern Many believe this to be a variation of acropigmentation of Kitamura Pigmented Anomalies of the Extremities

24. A rare pigmentary adult-onset disorder AKA Dowling-Degos disease or dark dot disease Should be considered whenever acanthosis nigricans is in the differential & pt is not obese and is known not to have any internal malignancy Clinically it looks smooth Pigmententation is reticular; at the periphery, discrete, brownish black macules surround the partly confluent central pigmented area Typically, axillae, inframmary folds, and intercrural folds are involved There are frequently pits, sometimes pigmented , about the mouth Reticular Pigmented Anomaly of the Flexures

25. It begins age 20 to 30 yrs and progresses gradually Unknown etiology AD with variable penetrance and expressivity, and delayed onset Many authors believe it is a spectrum of reticulate acropigmentation of Kitamura Another manifestation of this disorder is familial-rocacea-like dermatitis with warty keratotic plaques on the trunk and limbs There is no treatment Reticular Pigmented Anomaly of the Flexures

26. Distinctive elongation, tufting, and deep hyperpigmentation of therete ridges, with protrusion of similar tufts even from the sides of the follicles Histology

27. AD Characterized by linear palmar pits and pigmented macules 1-4 mm in diameter on the volar and dorsal aspects of the hands and feet One report of a pt with bony abnormalities consisting of absence of terminal phalanges of the second, third, and fourth toes Some tx success has been reported using axelaic acid ointment Reticulate Acropigmentation of Kitamura

28. Consists of a triad of generalized reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy Other associations: adermatoglyphia, hypohidrosis or hyperhidrosis, palmoplantar hyperkeratosis, and nonscarring blisters on dorsa of hands and feet. An autosomal dominant inheritance pattern has been reported. Dermatopathia Pigmentosa Reticularis

29. Dermatopathia Pigmentosa Reticularis

30. Infants develop 2- 3mm macules, pustules, and ruptured pustules at birth, predominantly involving the face Pigmentation may last for weeks or months after the pustules are healed Histologically, there are intracorneal or subcorneal aggregates of predominantly neutrophils, but eosinophils may also be found Dermal inflammation is composed of an admixture of neuts and eos Differential dx: ETN, neonatal acne, & acropustulosis of infancy Transient Neonatal Pustular Melanosis

31. Transient Pustular Neonatal Melanosis

32. Transient Neonatal Pustular Melanosis

33. Characterized by hyperpigmented macules on the lips and oral mucosa and polyposis of the small intestine Dark brown or black macules appear typically on the lips, especially the lower lip, in infancy or childhood Similar lesions may appear on buccal mucosa, tongue, gingiva, and genital mucosa Macules may also occur around the mouth, on the central face, backs of the hands, especially the fingers, and on the toes and tops of the feet. Associated polyposis involves the small intestine preferencely But, hamartomatous polyps of the stomach and colon may occur Symptoms of hamhartomas of the small intestine may cause repeated bouts of abdominal pain and vomiting, and intussusception Peutz-Jeghers

34. Cosmetic tx of labial macules has been accomplished with the use of a 694-mm ruby laser incidence of malignancy within the polyps is 2-3% Incidence of GI malignancy is low, but increased incidence of other kinds of cancer-breast, and gynecologic malignancies in women Syndrome is inherited and transmitted as a simple mendelian dominant trait Sporadic noninherited cases may occur The gene (STK11) has been localized to 19p13.3 19p13.3 is believed to be a tumor suppressor gene Peutz-Jeghers Syndrome

35. Cronkhite-Canada syndrome should be considered in dx Characterized by melanotic macules on the fingers and gastrointestinal polyposis Also generalized , uniform darkening of the skin, extensive alopecia, and onychodystrophy The polys that occur are usually benign adenomas and may involve the whole GI tract A protein-losing enteropathy may develop and is associated with the degree of intestinal polyposis Onset is after age 30 yrs Sporaically occurring, benign condition Hypogeusia is the dominant initial symptom Diarrhea and ectodermal changes may follow 75% of cases have been reported in Japan Peutz-Jeghers Syndrome

36. Peutz-Jeghers syndrome • Lip lentigenes in an adolescent with Peutz-Jeghers syndrome

37. P-J syndrome

38. Pathology

39. Photosensitivity, phototoxic dermatitis Begins with pruritis, erythema, and pigmentation, gradually spreads, then becomes stationary Melanosis occurs mostly in women and develops over months Characteristic feature is spotty light to dark brown pigmentation Most intense on the forehead, malar regions, behind the ears, on the sides of the neck, on other sun-exposed areas Also circumscribed telangiectasia and temporary hyperemia Reihl’s Melanosis

40. Sun exposure following perfume or cream A photocontact dermatitis One report of a positive patch test results to lemon oil, geraniol, and hydroxycitronellal Has been reported in patients with AIDS and Sjogren’s syndrome No good treatments The cause of the sensitivity needs to be determeined Hyperkeratosis and pigmentation disappear spontaneously pathogenesis

41. An occupational dermatosis occurring among tar handlers after years of exposure Severe, widespread itching develops, followed by reticular pigmentation, telangiectases, and a shiny appearance of the skin There is a tendency for hyperhidrosis Small, dark, lichenoid, follicular papules become profuse on the extremities, namely the forearms Bullae are sometimes observed Represents a photosensitivity or phototoxicity induced by tar Tar Melanosis

42. Characterized by patches of hyperpigmentation, present at birth, increasing in size and number with age Hyperpigmentation appears in the conjunctivae and the buccal mucosa over time Eventually large portions of skin and mucous membranes become involved AD inheritance Histologically- increase in melanin in the basal cell layer, especially at the tips of the rete ridges Pigmented granules are scattered diffusely throughout the epidermal layers Differentiated from other hyperpigmentations by presence of bizarre, sharply marginated patterns of hyperpigmented skin Familial Progressive Hyperpigmentation

43. Ruiz-Maldonado reported a case of a Mexican child, born white, who progressively became black Developed pigmentation of the palms, soles, mucous membranes EM showed a negroid pattern in the melanosomes of the epidermal melanocytes and keratinocytes Melanocytes were not increased in number Universal Acquired Melanosis(Carbon Baby)

44. Alimurung et al reported an unusual pattern of hyperpigmentation in a black male infant with congenital defects (ASD, dextrocardia, auricualr atresia, deafness. And growth retardation) Hyperpigmenation was linear and symmetrical, involving the trunk and extremities Increased number of melanocytes in the bands of hyperpigmentation Pigmentary anomaly fades with time spontaneously May be a varient of incontinentia pigmenti Zebralike Hyperpigmentation

45. 1.) Familial periorbital melanosis (AD) Usually involves all four eyelids, may extend to involve the eyebrows and cheeks 2.) Erythema dyschromicum perstans is a rare cause 3.) Familial dark circles around the eyes, frequently seen in individuals of Mediterranean ancestry Periorbital Hyperpigmentation

46. Metallic Discolorations • Pigmentation from deposition of fine metallic particles in the skin • Metal may be carried to skin from the blood stream or may permeate into it from surface applications

47. Localized or widespread slate-colored pigmentation Due to silver in the skin Most noticeable in parts exposed to sunlight Tissue silver may stimulate melanocytes Initially discoloration is hardly perceptible, having only a faint blue color, but a slate-gray color develops with time Local tx with a silver-containing product may produce argyria Examples: conjunctivae, from eye drops; a wound from sulfadiazine cream, earlobes from silver earings; and from silver acupuncture needles Can also occur from occupational exposure, usually siversmiths In localized exposures, the appearance may be separated by many years from the exposure Argyria

48. Histology • Systemic and localized argria have the same features • Normal appearing skin under low power • Fine black granules in the basement zone of the sweat glands,blood vessel walls, d-e junction, and arrector pili muscles • Unstained biopsy section by darkfield illumination demonstrates silver granules outlining basement membrane of the epidermis and the eccrine sweat glands

49. Bismuth • Rarely associated with deposition of metallic particles in gums when used IM or orally • Also known as the bismuth line • Presence of stomatitis or peridontitis increased the risk • Generalized cutaneous discoloration, in addition to oral mucous membrane and conjunctival pigmentation resembling argyria has occurred but has not be reported in the last 50 years

50. Lead • Chronic lead poisoning can produce a “lead hue” with lividity and pallor • Deposit of lead in the gums may occur and is known as the “lead line”