The lecture has been given on Apr. 10th, 2011 by Dr. Faraedon Kaftan.

1. Dermatologic Signs of Systemic Diseases5th yearLecture By Dr. FaraedonKaftanConsultant DermatologistCollege of MedicineUniversity of Sulaimani April. 10th2011

2. The skin is often a window to systemic disease. By recognizing cutaneous manifestations of systemic diseases, the internist can often determine the appropriate diagnosis and therapy or the need for referral to a dermatologist. 1- Common cutaneous disorders (Seb D, Seb K, Urt,EM, V, EN) 2- Blistering diseases (P, Pd, EBA) 3- Internal malignancies (Cut. Metastases, Pag. Dis, AN, Amyloid) 4- Cardiovascular disease (PXE, EDS) 5- Pulmonary disease (Sarcoidosis) 6- Rheumatic disease (Ps. A, LE, Sclerod., DM ) 7- Gastrointestinal disease (DH, ACE, LP …) 8- Renal disease (Nephrogenicfibrosingdermopathy) 9- Endocrine and metabolic disease (Porphyria and Diabetes Mellitus-Related Skin Conditions)

3. 1- Common cutaneous disorders Seborrheic dermatitis may be associated with systemic disease, such as 1-Parkinson's disease 2- (HIV: Human immunodeficiency virus) infection. 3- (CVA: cerebrovascular accident ) can develop unilateral seborrheic dermatitis on the scalp corresponding to the affected hemisphere, (The pathophysiology of this phenomenon is not completely understood.)

4. SeborrheicKeratoses the most common benign cutaneous neoplasms, are warty, age-related hyperkeratotic papules and plaques that appear anywhere on the body, most commonly the trunk. (Sign of Leser-Trélat):Rarely, if seborrheickeratoses appear suddenly in great numbers indicate an underlying adenocarcinoma of the GI tract

5. Urticaria or Hives are pruritic, edematous, evanescent wheals that resolve within 24 hours. Acute urticaria typically lasts less than 6 weeks. is most often caused by: 1- Medication (commonly penicillin or other antibiotics, sulfa drugs, aspirin) 2- Food (shellfish, nuts, chocolate), 3- infection: less often

6. ErythemaMultiforme (EM) Is a cutaneous hypersensitivity reaction characterized by Iris (Target) lesions on the face, hands and feet. is usually caused by: 1- Infection (herpes simplex virus or Mycoplasmapneumoniae) 2- and less commonly by drug sensitivity (sulfonamides, barbiturates, antibiotics).

7. Vitiligo commonly occurs in periorificial areas (mouth, orbits, vagina, anus) or at sites of trauma (hands, elbows, knees). Vitiligo is often associated with: 1- Autoimmune thyroid disease, 2- diabetes mellitus (Insulin-dependent) 3- Pernicious anemia, or 4- Addison's disease.

8. ErythemaNodosum (EN) Painful, erythematous nodules on the shins and occasionally elsewhere, in young women, between 20 and 40 years, lasting an average of 3 to 6 weeks. Causes of EN: 3 S + Tb 1- Streptococcal pharyngitis is the most common . 2- Tuberculosis, 3- (GI) infections with Yersinia, Salmonella, or Shigella, and 4- Systemic fungal infections. 5- Less common causes: drug sensitivity (sulfonamides, salicylates, iodides, oral contraceptives or hormone replacement therapy), and a variety of systemic diseases, most often inflammatory bowel disease (Crohn's disease more than ulcerative colitis) and sarcoidosis.

9. 2- Blistering diseasesPemphigusVulgaris painful mucosal erosions and flaccid skin blisters (bullae) that become erosive. occurs in the 40th to 60th of life, Mortality is significant, even with treatment.

10. BullousPemphigoid characterized by large, tense subepidermal blisters, which are often pruritic. Mucosal disease is rare. in the elderly, 65 and 75 years of age.

11. EpidermolysisBullosaAcquisita: EBA uncommon bullous disease characterized by skin fragility, milia (small cysts), scarring alopecia, and nail dystrophy. primarily on the hands, feet, elbows, and knees. EBA may be associated with other autoimmune diseases, most frequently inflammatory bowel disease.

12. 3- Internal malignancies Cutaneous Metastases Any malignant neoplasm can metastasize to the skin. in men: Cutaneous metastases are from cancers of the lung, large intestine, and kidney. in women: Cutaneous metastases are from cancers of the breast and large intestine. Flesh-colored to violaceous nodules in close proximity to the primary neoplasm; Most common sites are the - Head (scalp), - Neck, and - Trunk.

13. Paget's Disease 1- Mammary Paget's disease: Unilateral eczematous plaque of the nipple and areola. - is strongly associated with an underlying invasive Ca. of the breast 2- Extramammary Paget's disease: * persistent, eczematous plaque of the anogenital or axillary regions: * is often associated with an underlying - adnexal (apocrine gland) carcinoma or - cancer of the genitourinary tract or distal GIT.

14. AcanthosisNigricans (ANs) smooth, velvet-like, hyperkeratotic plaques in intertriginous areas (e.g., groin, axillae, neck). Type I (Malignant AN): is associated with malignancy. May be adenocarcinoma of the GI tract (60% gastric) has a sudden onset and more extensive distribution, including the face, palms, and trunk. Type III AN is associated with obesity and insulin resistance and is the most commonly occurring type. AN can develop following the use of drugs: systemic Cs, nicotinic acid, diethylstilbestrol, and isoniazid (INH).

15. Amyloidosis Purpuric and Ecchymotic Papules on the eyelids and extremities due to amyloid infiltration in the vessels. may be a sign of multiple myeloma.

16. 4- Cardiovascular diseasePseudoxanthomaElasticum: PXE Brittle (Broken)and calcified elastic fibers. Yellow papules over redundant skin folds on the neck, abdomen, and groin, giving the skin the appearance of plucked chicken skin. Angioid streaks in Bruch's membrane of the eye. Associated signs of PXE : 1- Hypertension (HTN) 2- Peripheral vascular and coronary artery disease 3- Retinal and GI hemorrhage 4- Stroke.

18. EDS

19. 5- Pulmonary disease Sarcoidosis is a multisystem, granulomatous disease of the lungs, bones, CNS, lymph nodes, eyes, and skin. more in women and in African Americans. Skin disease, affecting 25-35% of patients, includes (Lupus pernio): Red to purple indurated plaques of the nose midfacial papules annular plaques or nodules on the trunk and extremities. predilection for scars. Erythemanodosumis the most common manifestation.

20. 6- Rheumatic diseasePsoriatic Arthritis: (PsA) Affects 5-10% of patients with psoriasis. Asymmetric fusiform swelling of the distal interphalangeal joints (sausage digits) in 70%.

21. Lupus Erythematosus: DLE, SLE & SCLE (DLE) usually localized to the head or neck, is characterized by atrophic, scarring plaques on sun-exposed areas. 5% of patients develop SLE.

22. SLE cutaneous manifestations include Malarerythema (The butterfly rash): is the most common expression of SLE. Photosensitivity Oral ulcers Discoid plaques Bullae Purpura Calcinosis cutis alopecia.

23. systemic or generalized Scleroderma Are of 2 forms: 1- CREST syndrome: (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). - has a better prognosis 2- Progressive systemic sclerosis.

25. 7- Gastrointestinal disease Dermatitis Herpetiformis (DH) AcrodermatitisEnteropathica (ACE) Necrolytic Migratory Erythema(glucagonoma syndrome) Lichen planus (LP) Hereditary Hemorrhagic Telangiectasia (HHT) Peutz-Jeghers Syndrome PyodermaGangrenosum

26. Dermatitis Herpetiformis (DH) is a chronic, intensely pruritic blistering disease Most patients have an asymptomatic gluten-sensitive enteropathy less commonly thyroid disease.

27. AcrodermatitisEnteropathica (ACE) Is an inherited or acquired condition due to zinc deficiency. Acral and periorificial: pustules, bullae and scaling. Most patients have diarrhea. Treatment is zinc supplementation.

28. Necrolytic Migratory Erythema(glucagonoma syndrome) is rare, characterized by erythematous, scaly plaques on Acral, Periorificial or Intertriginous areas + hyperglycemia, diarrhea, weight loss, and atrophic glossitis. Is in association with an islet cell tumor of the pancreas. Treatment is rmoval of the tumor.

29. Lichen planus violaceous, flat, polygonal papules on the flexor aspects of the wrists, trunk, medial thighs, genitalia, and oral mucosa. May occur with: - Primary biliary cirrhosis - Hepatitis B virus immunization or - Gold therapy - In hepatitis C patients: Oral erosive lichen planus.

30. Hereditary Hemorrhagic Telangiectasia is an autosomal dominant disorder characterized by numerous telangiectases on the skin and oral mucosa. Recurrent epistaxisis the most common (85 - 90%) presenting manifestation. Telangiectases can involve the lungs, liver, brain, eyes, and GIThemorrhage can occur at any site. Pulmonary arteriovenous fistulae and central nervous system angiomas can also occur.

31. Peutz-Jeghers Syndrome lentigines (Lentigo: a brown pigmented spot ) on the skin (periorbital region, dorsal surfaces of the fingers and toes) and mucosa (lips, buccal mucosa) Associated with hamartomas (polyps) of the stomach, small intestine, and colon.

32. PyodermaGangrenosum painful ulcers with boggy, undermined edges and a border of gray or purple pigmentation. The ulcers often follow trauma (pathergy) and begin as pustules or nodules that ulcerate and extend centrifugally. legs are the most common site for the ulcers. 50% of patients have underlying rheumatoid arthritis or inflammatory bowel disease.

33. 8- Renal diseaseNephrogenic Systemic Fibrosis(Nephrogenicfibrosingdermopathy) Resembles scleroderma. Thick, indurated plaques on the extremities and the trunk. can be progressive, leading to joint contractures. In end-stage renal disease Patients on dialysis. Acute renal failure or After kidney transplantation.

34. 9- Endocrine and metabolic disease Porphyrias: are inherited or acquired disorders of heme biosynthesis. Erythropoietic, Hepatic, or mixed in nature. Porphyriacutaneatarda (PCT): is hepatic & the most common porphyria, Precipitating factors: alcohol ingestion, estrogen administration, certain hepatotoxins (dinitrochlorobenzene, carbon tetrachloride), HIV infection, hemochromatosis, and hepatitis C infection. Manifestations of PCT include: - photosensitivity - skin fragility - bullae and erosions on sun-exposed skin (especially dorsal hands), and hypertrichosis. Treatment includes phlebotomy and antimalarial drugs.

35. Diabetes Mellitus-Related Skin Conditions Cutaneous Manifestations of Diabetes Mellitus: from most to least common. 30-50% of diabetic patients develop skin disease. 1- Diabetic dermopathy (shin spots): Atrophic, hyperpigmentedpapules and plaques on the legs

36. 2- Diabetic thick skin: 3- Acanthosisnigricans: Common with obesity and diabetes 4- Yellow nails and skin (palms and soles): 5- Acquired perforating disorders 6- Calciphylaxis: isvascular calcification, thrombosis and skin necrosis: Painful purpuric plaques with ulceration 7- Necrobiosislipoidicadiabeticorum 8- Diabetic bullae