4  General Dermatology                                                        Priya Swamy Zeikus, MD                      ...
4.23	 Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113                            4.24	...
Committed to Your Future       For practice exam questions and interactive study         tools, visit the Dermatology In-R...
4.1 ACNE         VULGARISKey Pathogenic Factors       •	 Abnormal keratinization (follicular retention hyperkeratosis)    ...
•	 Dioxin (2,3,7,8 tetrachlorobenzodioxin) is a well-known, potent trigger of acneiform       eruptions5   Acneiform Erupt...
•	 Minocycline has been associated with CNS symptoms, including vertigo and headache,       autoimmune hepatitis, drug-ind...
•	 Screen for papilledema if headache, nausea, and vomiting        u TIP        occurs                                    ...
Granulomatous Rosacea     •	 Dozens of brown-red papules or nodules on diffusely reddened skin, frequently involving      ...
Phymas   Rhinophyma    •	 Occurs almost exclusively in men       1.)	 Gnathophyma – chin swelling       2.)	 Metophyma – f...
Guttate (Eruptive) Psoriasis      •	 Small (0.5 to 1.5 cm) lesions over upper trunk and proximal extremities      •	 Early...
   – Infection with HIV may represent another trigger factor      •	 Stress – psoriasis made worse by stress in 30-40% of...
•	 Nausea, dizziness, headache     •	 Photosensitivity during the 8-12 h after ingestion of psoralen, protective eyewear n...
Biologic Agents (see Table 4.1)      •	 Etanercept      •	 Efalizumab      •	 Alefacept      •	 Infliximab      •	 Adalimu...
4.4 Psoriatic         ArthritisFeatures   •	 20-40% of psoriatic patients; higher frequency found in moderate to severe ps...
Few patients present with classic triad, thus can be diagnosed with    •	 Peripheral arthritis  1 month duration    •	 Ass...
4.7 Sneddon-Wilkinson                    Disease                     u TIP                                                ...
Clinical Variants  Configuration  Annular LP    •	 Blacks more commonly affected    •	 On penis and scrotum    •	 Also, la...
Actinic LP    •	 More common in Middle Eastern countries in spring/summer    •	 Affects sun-exposed areas    •	 Typical LP...
Special Forms of LP/Lichenoid Eruption   Drug-induced LP     •	 May be typical or atypical for classic LP, localized or ge...
Associated Conditions   •	 Autoimmune chronic active hepatitis   •	 Primary biliary cirrhosis   •	 Postviral chronic activ...
•	 Orbital darkening      •	 Facial erythema or pallor      •	 Perifollicular accentuation      •	 Course influenced by en...
Foods    •	 Food allergens exacerbate skin rashes in at least a subset of patients with AD, particularly       infants and...
UV Phototherapy     •	 UVB useful adjunct to treatment of chronic recalcitrant AD     •	 High intensity UVA can be fast-ac...
•	 Totalis – total loss of scalp hair   •	 Universalis – 100% loss on scalp, eyebrows, eyelashes, and rest of body   •	 In...
Pseudopelade of Brocq   •	 Scarring alopecia where destruction of the hair follicle produces multiple round, oval, or     ...
4.12 Vitiligo   •	 Half of all cases begin before age 20   •	 Depigmented white patches surrounded by normal or hyperpigme...
4.13 Pityriasis       rubra pilaris   •	 Small follicular papules → salmon-orange to reddish-brown color, pinhead size, an...
Etiology   •	 Autoimmune phenomenon, likely   •	 20% of both men and women have at least one autoimmune disease (vitiligo,...
•	 Papules with central keratotic core representing transepidermal elimination of the      degenerated material in the cen...
Work-up    •	 Pelvic exam: Search for palpable ovarian masses    •	 Radiographic imaging of the pelvis/adrenal glands    •...
Secondary Systemic Amyloidosis   •	 Amyloid in the adrenals, liver, spleen, and kidney as a result of some chronic disease...
Table 4-2.  AmyloidosisTypes               Fibril Protein              Other FeaturesSystemicPrimary		       	   AL (lambd...
4.19 AngioedemaReview of the Complement System    Classic Pathway      •	 C1 binds to Fc fragment of IgM or IgG in immune ...
Diagnosis    •	 Screen with C3 and C4 levels → C4 low, C3 normal in angioedema   •	 C1q level low in acquired, but normal...
•	 Arthritis, psychiatric symptoms, osteoblastic bone lesions     •	 Fibrotic reactions affecting the valves of the heart ...
Treatment   •	 Sun avoidance   •	 Avoid exposure to heat, cold, trauma   •	 Topical corticosteroids (potent) with or witho...
Neonatal LE   •	 Annular scaling erythematous macules and plaques on head and extremities within the      first few months...
Pregnancy and SLE    •	 Miscarriages occur with greater frequency    •	 LE may worsen, or go into remission during pregnan...
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  1. 1. 4  General Dermatology Priya Swamy Zeikus, MD Bruce E. Strober, MD, PhD Katherine L. White, MDC o n t e n t s4.1 Acne Vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 764.2 Rosacea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 794.3 Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 814.4 Psoriatic Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 864.5 Reiter’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 864.6 SAPHO Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 874.7 Sneddon-Wilkinson Disease . . . . . . . . . . . . . . . . . . . . . 884.8 Lichen Planus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 884.9 Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 924.10 Alopecia Areata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 954.11 Alopecia: Other Forms . . . . . . . . . . . . . . . . . . . . . . . . . . 964.12 Vitiligo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 984.13 Pityriasis Rubra Pilaris . . . . . . . . . . . . . . . . . . . . . . . . . . . 994.14 Lichen Sclerosus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 994.15 Granuloma Annulare . . . . . . . . . . . . . . . . . . . . . . . . . . . 1004.16 Hirsutism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1014.17 Amyloidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1024.18 Calciphylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044.19 Angioedema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Carcinoid Syndrome and Flushing Disorders . . . . . 1064.20 4.21 Lupus Erythematosus . . . . . . . . . . . . . . . . . . . . . . . . . . 1074.22 Scleroderma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 (Continued on next page) General Dermatology  73
  2. 2. 4.23 Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 4.24 Sjogren’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 4.25 Connective Tissue Disease: Serology . . . . . . . . . . . . . 115 4.26 Relapsing Polychondritis . . . . . . . . . . . . . . . . . . . . . . . . 117 4.27 Behçet’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 4.28 Livedo Reticularis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 4.29 Leukocytoclastic Vasculitis . . . . . . . . . . . . . . . . . . . . . . 119 Cryoglobulinemia and Cryofibrinogenemia . . . . . . . 122 4.30 4.31 Acanthosis Nigricans . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 4.32 Lipodystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 4.33 Hyperlipoproteinemias . . . . . . . . . . . . . . . . . . . . . . . . . . 125 4.34 Xanthomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 4.35 Vitamin Deficiencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 4.36 Diabetes and Skin Disease . . . . . . . . . . . . . . . . . . . . . . 130 4.37 Langerhans Cell Histiocytosis . . . . . . . . . . . . . . . . . . . . 132 4.38 Cutaneous T-cell Lymphoma . . . . . . . . . . . . . . . . . . . . 133 4.39 Pyoderma Gangrenosum . . . . . . . . . . . . . . . . . . . . . . . . 136 4.40 Sweet’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 4.41 Erythema Annulare Centrifugum . . . . . . . . . . . . . . . . . 138 4.42 Erythema Elevatum Diutinum . . . . . . . . . . . . . . . . . . . . 138 4.43 Erythema Nodosum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 4.44 Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 4.45 Cutaneous Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . 142 4.46 Perforating Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 144 4.47 Elastosis Perforans Serpiginosa . . . . . . . . . . . . . . . . . 144 4.48 Reactive Perforating Collagenosis . . . . . . . . . . . . . . . 145 Cutaneous Features and Disorders of Pregnancy . . 145 4.49 4.50 Pruritus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 4.51 Scleredema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 4.52 Nephrogenic Fibrosing Dermopathy/ Nephrogenic Systemic Fibrosis . . . . . . . . . . . . . . . . . 14974  2011/2012 Dermatology In-Review l Committed to Your Future
  3. 3. Committed to Your Future For practice exam questions and interactive study tools, visit the Dermatology In-Review Online Practice Exam and Study System at DermatologyInReview.com/GaldermaSponsored by
  4. 4. 4.1 ACNE VULGARISKey Pathogenic Factors • Abnormal keratinization (follicular retention hyperkeratosis) • Inflammation • Presence of Propionibacterium Acnes (P. acnes) in sebum • Sebum production, under hormonal control, starting at adrenarchePathogenesis Overview • Precursor lesion of comedonal and inflammatory acne is the microcomedo • Human sebum is rich in triglycerides.1 P. acnes makes an enzymatic lipase which cleaves triglycerides into free fatty acids • Inflammation is triggered by follicular wall rupture and subsequent immune response. P. acnes itself is pro-inflammatory; it can activate complement, and neutrophil chemotaxis and activity • IL-1, a pro-inflammatory cytokine, may promote follicular plugging and microcomedo formation2 • Toll-like receptors (TLR’s) → a large group of receptors that recognize certain bacterial patterns. TLR-2 activation by P. acnes leads to intracellular signal transduction and upregulation of the immune response by stimulating pro-inflammatory cytokines.3 Certain topical retinoids have been shown to downregulate TLR-2 expression4Clinical Variants Acne Vulgaris • Noninflammatory lesions are the microcomedo and the comedo (open and closed) • Inflammatory lesions are papules, pustules and nodules Acne Conglobata • A severe variant characterized by large, often multiple comedones, abscesses with sinus formation, and inflammatory nodules • Seen most frequently in young male patients • Follicular occlusion triad consists of acne conglobata, hidradenitis suppurativa, and dissecting cellulitis of the scalp. Treatment is with high dose isotretinoin Acne Fulminans • A rare, explosive form of severe cystic acne affecting young males • Marked by acute, suppurating nodules and plaques that ulcerate and form blackish eschar • The trunk is affected more severely than the face  • Patients may be systemically ill, with leukocytosis, fever, arthralgias, and myalgias. Lytic changes, indicative of a sterile osteomyelitis, can be seen on x-ray and bone scans. The sternoclavicular joint and the chest wall are most frequently affected • Treatment is with oral prednisone, intralesional steroids, antibiotics, and isotretinoin Miscellaneous Acne Variants Industrial Acne  • Chloracne is a form of industrial acne triggered by workplace exposure to chlorinated compounds •  he malar cheeks and postauricular scalp, as well as the scrotum, are affected. The lesions  T  are characterized by large comedones as well as inflammatory papules, pustules, and cysts • Insoluble cutting oils are the most frequent cause of industrial acne76  2011/2012 Dermatology In-Review l Committed to Your Future
  5. 5. • Dioxin (2,3,7,8 tetrachlorobenzodioxin) is a well-known, potent trigger of acneiform eruptions5 Acneiform Eruptions • Numerous oral agents have been associated with acneiform eruptions, including the halogens bromide and iodide, androgenetic hormones such as testosterone, ACTH, corticosteroids, isoniazid (INH), lithium, erbitux, phenytoin, cyclosporine, and Vitamins B2, B6, and B126Treatment of Acne Vulgaris Topical Retinoids • Tretinoin (all trans-retinoic acid), adapalene, and tazarotene are effective comedolytic agents which normalize follicular epithelial differentiation • Retinoid activity is mediated by retinoid receptors. Two groups exist: RA receptors (RAR) and RX receptors (RXR). Each has three receptor subtypes: α, β, γ. RAR-γ is the most important mediator of retinoid activity in the skin • Tretinoin and adapalene are pregnancy category C drugs; tazarotene is category X. Tretinion activates RAR receptors α, β, γ. Bexarotene selectively binds retinoid X receptors. Adapalene activates RAR β and γ. Tazorac binds RAR α, β, γ but shows selectively for RAR β and RAR γ Topical Antibiotics (Erythromycin and clindamycin)  • Decrease the population of P. acnes on the skin • Increasing antibiotic resistance has discouraged their use as monotherapy Benzoyl Peroxide (BPO) • Bactericidal agent with direct oxidizing effects, and thus no potential for resistance • Irritation, dryness, and bleaching of clothing or hair may occur Combination Products (Clindamycin or Erythromycin and BPO) • Synergistic efficacy and decreased potential for antibacterial resistance • May cause irritation Azelaic Acid • Dicarboxylic acid that has weak activity against P. acnes • Inhibits tyrosinase, and can be helpful in reducing post-inflammatory pigment alteration. Itching, burning or dryness at the initiation of treatment is not uncommon • Pregnancy category B Oral Antibiotics Tetracyclines • Tetracycline, doxycycline, and minocycline • Inhibit RNA-dependent protein synthesis by binding the bacterial 30s ribosomal subunit • Tetracycline is best absorbed on an empty stomach, and its absorption is inhibited by chelation with bi- and trivalent cations (e.g., calcium, bismuth, iron) • Tetracycline can cause permanent brown discoloration of the teeth in children, and is not used routinely for children under the age of eight • Risk of photosensitivity Demecycline Doxycycline Tetracycline Minocyline • Photo-onycholysis has been reported with Tetracycline  • Unlike other tetracyclines, doxycycline is excreted via the GI tract rather than the kidneys, and thus is the tetracycline of choice in renally compromised patients 8 General Dermatology  77
  6. 6. • Minocycline has been associated with CNS symptoms, including vertigo and headache, autoimmune hepatitis, drug-induced anti-histone Ab positive SLE-like syndrome, and hyperpigmentation • Minocycline can cause hyperpigmentation of the skin. Three types are generally  described: - Blue-Black Discoloration: Appearing in areas of prior skin injury, such as acne scars - Blue-Gray Discoloration: Often at the lower anterior legs and forearms - Muddy Brown Discoloration: Found on sun-exposed areas. The least common type of hyperpigmentation • The first two types show staining for both iron and melanin [Fontana Masson stains melanin black; Perls stain stains iron (hemosiderin) blue]. The third type shows increased melanin at the basal layer and within macrophages • Doses of tetracyclines below the minimum inhibitory concentration (MIC) can inhibit neutrophil chemotaxis, pro-inflammatory cytokine cascades, and reduce P. acnes production of lipase Macrolides • Include erythromycin and azithromycin • Inhibit RNA-dependent protein synthesis by binding the 50s ribosomal subunit • Erythromycin can cause gastrointestinal distress and potentially significant drug interactions • Erythromycin inhibits the hepatic cytochrome P450 system and can increase serum levels and potential toxicities of carbamazepine, theophylline, warfarin, digoxin, methylprednisolone Trimethoprim-sulfamethoxazole (TMP-SMX) • Considered second-line therapy for acne, due to increased risk of serious adverse reactions, including hypersensitivity reactions • TMP-SMX inhibits bacterial folic acid synthesis • Drug hypersensitivity syndrome is characterized by fever, skin eruption and internal organ involvement Isotretinoin • Gold standard for treating nodular acne and recalcitrant acne • Reduces sebum production by reducing sebaceous gland size, normalizes follicular keratinization, and indirectly reduces P. acnes and its inflammatory sequelae • A potent teratogen • Half-life of isotretinoin is 10-20 hours13 • Doses range from 0.5-2.0 mg/kg/day for 4 to 6 months (or 120-150 mg/kg total dose) • Patients are monitored monthly for changes in the plasma lipids, liver function tests and complete blood counts. Monthly pregnancy tests for women are also required. The most common laboratory abnormalities are increased triglycerides, followed by elevation of ALT and AST; decreased blood counts are rare; increased exercise can cause elevation of creatinine phosphokinase • Almost all patients experience cheilitis, xerosis, dry nasal mucosa, dry eyes • Other, less common side effects: hair thinning (usually reversible), skin infection, petechiae, abdominal pain, corneal opacities, bone and joint pain, headache, diffuse idiopathic skeletal hyperostosis (DISH)78  2011/2012 Dermatology In-Review l Committed to Your Future
  7. 7. • Screen for papilledema if headache, nausea, and vomiting u TIP occurs aseudotumor cerebri occurs P more often with co-adminis- • Recent reports of serious psychiatric events possibly related tration of a tetracycline to isotretinoin have drawn considerable attention. A large population based study with control groups failed to show an increased risk of depression, suicide attempt and suicide among isotretinoin treated patients14 Hormonal Therapies • May be an important component of acne treatment in the female patient, especially for adult women with a predominance of acne at the lower face • Most common endocrinopathy associated with acne is polycystic ovary syndrome (PCOS), characterized by acne, obesity, hirsutism, amenorrhea and glucose intolerance • Congenital adrenal hyperplasia (CAH) is also associated with acne • Although rare, very high levels of DHEA-S may suggest an adrenal androgen-secreting tumor • A patient whose acne fails to respond to conventional therapy, whose acne flares cyclically, with hirsutism, alopecia or irregular menses warrants an endocrine work-up, including free and total testosterone, LH, FSH, and DHEA-S • Benefit from hormonally-based therapies, such as oral contraceptives (OCPs) • Usually ethinyl estradiol. OCP’s lead to a decrease in free testosterone levels by increasing the adrenal production of sex hormone binding globulin (SHBG) • Spironolactone, commonly dosed between 50 to 200 mg/day → blocks androgen receptors and adrenal androgen synthesis. Side effects include menstrual irregularities, breast tenderness, and intestinal symptoms, which can be mitigated by concomitant OCP use. Hyperkalemia is more likely in the setting of renal failure. Spironolactone is not FDA- approved for the treatment of acne. It is pregnancy category X4.2 Rosacea • Papules and papulopustules in central region of face against a vivid background of telangiectases. Later, diffuse hyperplasia of connective tissue with enlarged sebaceous glands • Localized to nose, cheeks, chin, forehead, glabella; less commonly affected areas include the retroauricular, V-shaped chest area, neck, back, scalp • Flushing and blushing evoked by UV, heat, cold, chemical irritation, strong emotions, alcoholic beverages, hot drinks, and spicesVariants of Rosacea Persistent Edema of Rosacea (Rosacea Lymphedema or Morbihan’s Disease) • Hard, nonpitting edema • Often misdiagnosed as cellulitis Ophthalmic Rosacea • Blepharitis, conjunctivitis, iritis, keratitis (inflammation of cornea) • The treatment of choice for ocular rosacea is oral antibiotics General Dermatology  79
  8. 8. Granulomatous Rosacea • Dozens of brown-red papules or nodules on diffusely reddened skin, frequently involving lower eyelids • Histopathology: perifollicular and perivascular noncaseating epithelioid granulomas • Chronic and unremitting Steroid Rosacea • Rosacea resulting from steroid use • Steroid atrophy with resultant telangiectases • Flaming red, scaling, papule-covered face • Severe pain, discomfort • Withdrawal of steroid accompanied by exacerbation of disease • Slow tapering of steroid over months is required Rosacea Fulminans (Pyoderma Faciale) • Occurs almost exclusively in post-adolescent women; lots of flushing and blushing • Large coalescent nodules and confluent draining sinus occupy most of the face • Prognosis is excellent, and recurrences rare Perioral Dermatitis • May be triggered or exacerbated by topical steroid use • Generally responds well to topical and/or oral antibiotic treatmentTreatment Topical • Antibiotics – often effective – Topical clindamycin and erythromycin – Topical metronidazole active against papules and pustules, but not telangiectasia and flushing – Topical sulfur-based preparations • Azelaic acid • Sunscreens • Green-tinted makeup concealer can neutralize redness Systemic • Antibiotics – generally responds well – Tetracyclines – Erythromycin • Isotretinoin – indicated in phymas; but rosacea often rapidly recurs after discontinuation of isotretinoin Treatment for Rosacea Fulminans • Oral glucocorticoids, 1.0 mg/kg per day for 7-10 days, add isotretinoin, with slow tapering of steroid, for 3-4 months until all inflammatory lesions disappear • Do not incise draining abscesses • Topical steroids (potent) for first two weeks80  2011/2012 Dermatology In-Review l Committed to Your Future
  9. 9. Phymas Rhinophyma • Occurs almost exclusively in men 1.) Gnathophyma – chin swelling 2.) Metophyma – forehead and nose saddle 3.) Otophyma – earlobes 4.) Blepharophyma – eyelids4.3 Psoriasis Psoriasis is an immune dysregulatory disease resulting from persistent T-cell activation andthe resultant release of TH1-based cytokines such as TNF-α and IL-2. These cytokines cause kera-tinocytic proliferation (acanthosis), and increased recruitment of inflammatory cells into the psori-atic skin.Epidemiology • Affects approximately 2% of population of U.S. • Usually begins in 3rd decade of life. Bimodal incidence: peaks at ages 29 and 55 • An early onset predicts more severe disease. Also, early onset more likely with positive family historyInheritance • Increased incidence in offspring of parents in which one or both affected • Monozygotic twin concordance HLA association with • HLA-B13 • HLA-B17 (earlier onset and more serious disease) • HLA-Bw57 • HLA-Cw6 (most definitive associated HLA type) – relative risk 9-15 times normal • Psoriatic arthritis in disequilibrium with HLA-B27, especially if spondylitis presentClinical Features Skin Lesions • Sharply demarcated papules and plaques • Non-coherent silvery scales • Auspitz sign → bleeding upon removal of scale • Koebnerization seen in 20% • Woronoff Ring: Area of blanching around psoriatic plaques secondary to decrease in prostaglandin, PGE2Clinical Patterns Chronic Stationary/Psoriasis Vulgaris • Most frequent • Red, scaly lesions persist for years • Little alteration in shape/distribution of plaques • Areas of predilection: elbows, knees, scalp, retroauricular region, lumbar, umbilicus • When localized in the major skin folds, scaling is absent General Dermatology  81
  10. 10. Guttate (Eruptive) Psoriasis • Small (0.5 to 1.5 cm) lesions over upper trunk and proximal extremities • Early age of onset/young adults  • Streptococcal throat infection frequently precedes eruption Psoriatic Erythroderma • Affects all body sites • Erythema is most prominent feature, scaling less prominent Generalized Pustular Psoriasis  • Von Zumbusch type; acute variant • Usually no other forms on skin at same time  • Fever, lasting several days, with eruption of sterile pustules 2-3 mm diameter paralleling the fever • Distribution: Trunk, extremities including nail beds, palms, and soles • Pustules arise on highly erythematous skin • Fingertips may become anonychic and atrophic  • Hypocalcemia, hypoalbuminemia, leukocytosis Localized Pustular Psoriasis • Systemic symptoms absent • Two distinct conditions 1.) Pustulosis palmaris et plantaris 2.) Acrodermatitis continua of Hallopeau Psoriatic Nail Disease • May be of nail matrix or nail bed origin • Fingernails involved in 50%, toenails in 35% • Nail changes more frequent (80-90%) in patients with arthritis  • Psoriatic nail changes of matrix → pits (the most common nail change of psoriasis and representing focal psoriasis of the proximal matrix) and leuconychia • Pits in psoriasis are generally more randomly distributed than the regular rows of pits seen in alopecia areata • Psoriatic nails changes of nail bed origin include: salmon spots, “oil spots,” onycholysis, subungual hyperkeratosis, and splinter hemorrhages16 Psoriatic Arthritis • Asymmetric oligoarthritis, small joints of hands • Associated onycholysis Trigger Factors • Warmer weather and sunlight reported to be u TIP beneficial a rugs D • Physical trauma – Koebner reaction –  teroids – withdrawal of systemic and S • Infection possibly topical) corticosteroids can result in severe flares – 50% of children exacerbate existing psoriasis – Lithium during 2-3 week interval after URI – Beta-blockers –  cute guttate psoriasis frequently follows an A – Interferons  – ACE inhibitors acute streptococcal infection by 1-2 weeks (56- – Granulocyte-colony stimulating factors17 85%) and streptococcal infections may play a role a ntimalarials and NSAIDS are not elieved to A in exacerbating other forms of psoriasis truly exacerbate psoriasis in most patients82  2011/2012 Dermatology In-Review l Committed to Your Future
  11. 11.  – Infection with HIV may represent another trigger factor • Stress – psoriasis made worse by stress in 30-40% of casesSystemic Associations • Psoriatic arthritis • Crohn’s disease and ulcerative colitis • HTN, obesity, diabetes, and chronic oropharyngeal infections found more frequently in psoriatic patients • Pustular psoriasis associated with HLA-B27, and arthropathy is common • Increased risk of lymphomaKeratinocyte Proliferation • 8-fold shortening of epidermal cell cycle (36 hrs vs. 311 hrs for normal)Treatment Anthralin (topical) • Advantage: lacks long-term side effects • Possesses antiproliferative activity on human keratinocytes • Also, strong anti-inflammatory effects by inhibiting PMNs and monocytes • Irritant reactions, especially after increasing concentration too fast • Can stain hair to purple • Brownish discoloration of surrounding skin—reversible Vitamin D3 Analogues • Calcipotriol, tacalciol, calcitriol • Inhibit keratinocyte proliferation and induce terminal differentiation • Anti-inflammatory • Used for plaque-type psoriasis QD or BID • Calcipotriol inactivated by salicylic acid or lactic acid (Lac-hydrin) • Should be used after UV-light (calcipotriol absorbs UV) • Local irritation Tazarotene • Retinoid • Reduces scaling and plaque thickness, with little effectiveness on erythema • May be beneficial in combination with phototherapy Tar • Unknown activity • 2-5% tar in various bases effective in chronic plaque-type psoriasis Topical Glucocorticoids PUVA • Oral ingestion of a potent photosensitizer such as 8-methoxypsoralen (8-MOP) or trimethoxypsoralen (0.6 mg/kg) and variable doses of UVA, 2 hours after ingestion • Treatments given TIW or QIW • Clearing usually occurs after 19 to 25 treatments • Overdosing results in sunburn, 24-48 hour post-treatment • Psoralens → intercalate with DNA, with energy of UVA covalently cross-link nucleic acids between opposing strands of duplex regions, leads to irreversible photo-inhibition of DNA synthesis and mitosis General Dermatology  83
  12. 12. • Nausea, dizziness, headache • Photosensitivity during the 8-12 h after ingestion of psoralen, protective eyewear needed  • Higher frequency of squamous cell carcinomas, and perhaps malignant melanoma risk, increases after 250 treatments Methotrexate  • Synthetic analog of folic acid that competitively inhibits dihydrofolate reductase • Inhibits S phase of cell cycle (like hydroxyurea) • 10-30 mg once per week PO or IM • Nausea, anorexia, fatigue, headaches, alopecia, stomatitis • Leukopenia and thrombocytopenia indicate overdose → leucovorin rescue required • Careful in kidney dysfunction → renal excretion • Acute interstitial pneumonitis (rare) • Hepatotoxicity; exclude those with liver disease or alcohol abuse; above a cumulative dose of 1.5 g, liver biopsy is often recommended before continuing with therapy • Also effective in treating psoriatic arthritis Cyclosporine  • Inhibits release of cytokines, specifically IL-2, by binding and deactivating calcineurin • Effective in erythrodermic and generalized pustular psoriasis • Start at 2.5 to 4 mg/kg per day, and can go as high as 5.5 mg/kg per day • Renal impairment (often reversible) → reduce dosage by 25% if creatinine increases to 30% or greater of baseline • Hypertension (Treat with ACE-inhibitors) • Elevated triglycerides • Hyperkalemia • Hypomagnesemia • Hepatotoxicity • Hypertrichosis (common), gingival hyperplasia, trichomegaly, nausea, vomiting, diarrhea, arthralgia, myalgia, tremor, acne, sebaceous hyperplasia, and fatigue may occur • Long-term risk of malignancy • Metabolized by P450, thus erythromycin or ketoconazole will increase drug levels Retinoids → Acitretin • Vitamin A derivatives • Effective in pustular and palmoplantar forms of psoriasis • Acitretin is most commonly used, given at 25 mg per day initially • Restrict use in women of childbearing age • Regulate growth and terminal differentiation of keratinocytes; modulate transcription of specific genes through retinoid response elements • Show lower response rates than other systemic modalities for treatment of plaque-type psoriasis → often ineffective as monotherapy for plaque-type psoriasis  • Effective when combined with ultraviolet phototherapy (either UVB or PUVA) • Treatment over 3-4 months necessary • Dose related adverse effects: cheilitis, sicca symptoms of eyes and mouth, generalized pruritus, dry skin, loss of stratum corneum of palms and soles, hair loss • Muscle and joint pain • Elevation in serum lipids, and also LFTs • Monitor liver and kidney function, blood glucose, lipid profile84  2011/2012 Dermatology In-Review l Committed to Your Future
  13. 13. Biologic Agents (see Table 4.1) • Etanercept • Efalizumab • Alefacept • Infliximab • Adalimumab • Ustekinumab Table 4-1. BiologicsDrug Mechanism Labs Pregnancy Other ClassEtanercept Recombinant fusion protein to TNF 50 mg SC injections B receptor; binds soluble TNF-alpha twice weeklyEfaluzimab Humanized antibody that binds CD11a Weekly SC C component of LFA1 which binds to injections ICAM1 on APC and endothelial cellsAdalumimab Antibody towards human TNF-alpha Self administered IM B injection qoweekAlefacept Protein that blocks the interaction of IM injections once CD4 B LFA3 and Fc human IgG, LFA3 is the weekly or once counts receptor for CD2 and increased in weekly IV bolus CD45 Ro T cellsInfliximab Monoclonal antibodies which inhibit IV injections, first B Contraindicated TNF-alpha dose followed by in CHF, may dose at weeks 2, 6, cause drug then dosed 8 weeks induced SLEUstekinumab Human antibody that blocks IL-12 and SC injections once, PPD B IL-23 then in 4 weeks then in 12 weeks Systemic Glucocorticoids • Systemic steroids are very rarely used in the treatment of psoriasis as many better alternative therapies exist • Severe rebound psoriasis can occur after discontinuation • Chronic use leads to well-characterized side effects of systemic corticosteroid use Combination Therapies • Often desirable, as combinations can limit the toxicities of individual therapies; examples: – Topical steroids with UVB or PUVA – Retinoids with PUVA or narrow band UVB – Vitamin D analogues with UVB – Ingram method: coal tar baths, UVB, anthralin – Methotrexate with UVB – Methotrexate with cyclosporine – Etanercept with methotrexate Phototherapy, conventional systemic agents, and biologic agents treating psoriasis are dis-cussed elsewhere in this text. General Dermatology  85
  14. 14. 4.4 Psoriatic ArthritisFeatures • 20-40% of psoriatic patients; higher frequency found in moderate to severe psoriasis patients • Age of onset: 18–50 years • Usually (80%) rheumatoid factor negative (seronegative) • Synovial, serum and lesional levels of TNF-α are increased in psoriasis and psoriatic arthritis18Types of Psoriatic Arthritis • Asymmetric oligoarthritis or polyarthritis (most common) • Symmetric polyarthritis (RA-like) • Spondylitis (axial) • Distal interphalangeal joint (DIP) disease • Arthritis mutilans (least common) • Enthesopathy (inflammation of ligaments and tendons at insertion point on bones)19Clinical • Morning stiffness of joints lasting more than 60 minutes • Inflammation of DIP joints → often with nail involvement (~80%) • Dactylitis: “sausage digits” • Enthesitis/Enthesopathy → Inflammation of tendons or ligaments or at sites of tendon insertion into bone • Spondylitis/sacroiliitis and axial disease • Reduced range of motion of shoulders, neck, and lower back • 80% of patients present with skin disease firstRadiographic Features of Psoriatic Arthritis • “Sausage digits” • Large eccentric erosions • Pencil-in-cup deformities—erosive changes of the joint: phalangeal distral tip is pencil on an eroded cuplike joint space • Tuft resorption: (acroostcolysis) • Periostitis: inflammation of the periosteum • SacroileitisTherapy for Psoriatic Arthritis • NSAIDs • Sulfasalazine • Methotrexate • Etanercept (FDA-approved therapy) • Ustekinumab (awaiting FDA approval)4.5 Reiter’s Syndrome Chronic inflammatory disease similar to psoriasis with psoriatic arthritis. • Urethritis • Conjunctivitis • Arthritis86  2011/2012 Dermatology In-Review l Committed to Your Future
  15. 15. Few patients present with classic triad, thus can be diagnosed with • Peripheral arthritis 1 month duration • Associated urethritis (or cervicitis) Occurs in young men of HLA-B27 genotype. Rarely occurs in women.Clinical • Any one of triad • Fever, weakness, and weight loss • Nonbacterial urethritis with painful and bloody urination and pyuria • May involve gastroenteritis • Cystitis, prostatitis, seminal vesiculitis • Keratitis may lead to corneal ulceration • Iritis common • Arthritis is asymmetric • Endocarditis, pericarditis, myocarditis, aortic insufficiency • Erythema nodosumSkin Lesions • Multiple small, yellowish vesicles that break, become confluent, and form superficial erosions → frequently on genitals and palms • Crusted, hyperkeratotic papules and plaques on plantar surfaces → keratoderma blennorrhagicum • Penile lesions: Perimeatal balanitis; circinate lesions; similar lesions seen on vaginal mucosa of affected women • Buccal, palatal, and lingual mucosa may show painless, shallow, red erosions, and severe stomatitis • Nails become thick and brittle with heavy subungual hyperkeratotic depositsEtiology • Chlamydia trachomatis associated with cases involving infection of GU tract • HLA-B27 in 80% of cases u TIPTreatment a • Topical steroids Shigella flexneri (most common) of nonurethral form of Reiters, • NSAIDs Salmonella spp., Yersinia spp., • Methotrexate Ureaplasma urealyticum, Borrelia • Acitretin burgdorferi, Cryptosporidia, Campylobacter fetus • Cyclosporine • TNF-inhibiting biologics such as etanercept • Course of disease marked by exacerbation and remission. A chronic deforming arthritis occurs in 20%4.6 SAPHO Syndrome • Synovitis • Acne (Acne fulminans or conglobata) • Pustulosis (pustular psoriasis) • Hyperostosis • Osteomyelitis General Dermatology  87
  16. 16. 4.7 Sneddon-Wilkinson Disease u TIP a ssociation with IgA monoclonal A • Subcorneal pustular dermatosis gammopathy • Middle-aged women • Superficial pustules in annular and serpiginous patterns • Abdomen, axillae, groin • Pustules are sterileHistology • Pustules form below stratum corneum without acantholysis • Contains many neutrophilsTreatment • Dapsone • Acitretin • Narrow band UVB Chronic condition, possibly related to psoriasis, with remissions of variable duration.4.8 Lichen Planus Inflammatory disorder that affects the skin, mucous membranes, nails, and hair. • Purple, polygonal, pruritic, papule, planar • Scaling is not as prominent as other papulosquamous diseases • Prevalence: 1%, no racial preference • 2/3 cases between ages of 30 and 60Etiology and Pathogenesis Classification Scheme • Idiopathic (classic) • Drug associated • Associated with other diseases (Ulcerative Colitis, Alopecia Areata, Vitiligo, Dermatomyositis, Myasthenia Gravis)Role of Infection • Hepatitis C implicated in triggering LP • Association with syphilis, HSV2, HIV, amebiasis and chronic bladder infectionsClinical Manfiestations • Erythematous to violaceous, flat-topped, polygonal papule, with occasional small central umbilication • Thin, transparent, adherent scale atop the lesion • Wickham’s striae – fine, whitish reticulated networks on surface of well-developed plaques • LP begins as erythematous macules that evolve over weeks; initial lesions always appear on the extremities • Generalized eruption develops over one to four months • Symmetrically involves flexural areas of wrists, arms, legs; also, oral mucosa and genitalia • Inverse LP: Axillae, groin, inframammary areas • LP is usually pruritic; oral involvement generally asymptomatic, unless erosive → extremely painful • Koebnerization (isomorphic response) occurs88  2011/2012 Dermatology In-Review l Committed to Your Future
  17. 17. Clinical Variants Configuration Annular LP • Blacks more commonly affected • On penis and scrotum • Also, larger lesions reach 2-3 cm in diameter and become hyperpigmented with raised outer rim Linear LP • Secondary to trauma, often Hypertrophic LP • Shins, interphalangeal joints • Most pruritic • Heals with scar formation and hyper/hypopigmentation Atrophic LP • Rare • White, bluish papules or plaques with central superficial atrophy • Most common lower extremities and trunk • Resembles lichen sclerosus et atrophicus Vesiculobullous LP • Rare • Vesicles and bullae within lesions of LP • Bullae arise from papules of LP, not normal skin • Subepidermal separation Erosive Ulcerative LP • Chronic and painful bullae and ulcerations on feet • Usually associated with more typical LP lesions of nails, mucosal surfaces and skin • Loss of toenails and alopecia common u TIP  • SCC may develop in lesions of ulcerative LP, a therefore biopsy may be indicated Erosive mucous membrane disease more • In oral LP, oral mucosa, gingiva and tongue may be common in patients with Hepatitis C infection affected. Desquamative gingivitis may occur • Histology of mucosal LP differs from LP of the skin in that parakeratosis rather than orthokeratosis is seen, secondary to the lack of granular layer on mucosal surfaces21 Follicular LP (lichen planopilaris) • Individual keratotic and follicular papules and studded plaques • Trunk and medial aspects of proximal extremities • Affects scalp – cicatricial alopecia  • Graham-Little-Piccardi-Lassueur syndrome: triad of 1.) Follicular LP of skin and/or scalp 2.) ultifocal cicatricial alopecia of scalp M 3.) onscarring alopecia of axillary and pubic areas N Lichen Planus Pigmentosus • Uncommon • Hyperpigmented, dark brown macules in sun-exposed areas and flexural folds • Occurs in darker-pigmented people • Similar to erythema dyschromicum perstans General Dermatology  89
  18. 18. Actinic LP • More common in Middle Eastern countries in spring/summer • Affects sun-exposed areas • Typical LP may be seen over extremities • Pruritus and scaling minimalSites of Involvement LP of the Scalp • Lichen planopilaris or follicular LP: individual keratotic papules that coalesce and merge to form patches • Women men • Uni- or multifocal hair loss • End-stage: scarring alopecia • Pseudopelade of Brocq: scarring alopecia and fibrosis; end stage of follicular fibrosis caused by primary inflammatory dermatosis such as LP, LE, pustular scarring forms of folliculitis, favus, scleroderma, and sarcoidosis Mucosal LP • Affects mouth, vagina, esophagus, conjunctiva, urethra, anus, nose, and larynx • 60-70% patients with LP • Only manifestation of LP in 20-30% • Forms: reticular, plaque-like, atrophic, papular, erosive-ulcerative, and bullous forms • Male genitalia: 25% of cases, glans penis most common site (annular lesions, frequently) • Female genitalia: leukoplakia/erythroplakia, erosive, or generalized desquamative vaginitis • Vulvar and gingival LP can exist together – erythema and erosions of gingivae and tongue and white reticulated plaques • Conjunctival LP: cicatricial conjunctivitis LP of the Nails • 10-15% of cases • Usually in combination with other LP lesions on skin • 20-nail dystrophy (trachyonychia) can be seen, but trachyonychia is not diagnostic of LP • Thinning, longitudinal ridging, and distal splitting of nail plate (onychoschizia) • Also, oncholysis, longitudinal striation (onychorrhexis), subungual hyperkeratosis, or anonychia • Classic finding: dorsal pterygium or forward growth of the eponychium with adherence of proximal nail plate; also “tenting” sign as nail plate elevated with longitudinal splitting • Pits common Inverse LP • Rare • Occurs in flexural areas such as axilla, under breast, groin • Reddish-brown, discrete papules Palmoplantar LP • Yellowish, compact keratotic papules and papulonodules on lateral margins of fingers and hand surfaces90  2011/2012 Dermatology In-Review l Committed to Your Future
  19. 19. Special Forms of LP/Lichenoid Eruption Drug-induced LP • May be typical or atypical for classic LP, localized or generalized • Typically manifest postinflammatory hyperpigmentation, alopecia, without Wickham’s striae • Symmetric eruption on trunk and extremities—photodistribution common with these drugs: 5-FU, carbamazepine, chlorpromazine, diazoxide, ethambutol, quinine/quinidine, tetracyclines, thiazides and furosemide • Mucous membrane involvement often associated with specific drugs and chemicals— amalgam containing mercury; gold more common LP–Lupus Overlap • Classic lesions of LP not usually seen • Photosensitivity, pruritus, follicular plugging also uncommon • Lesions on extremities, commonly: atrophic plaques and patches with hypopigmentation and a livid red-to-blue violet color with telangiectasia and minimal scaling; bullae may develop • May progress to SLE • Prolonged course • Histo: Lichenoid reaction and histologic features of LE seen in same biopsy Lichen Planus Pemphigoides u TIP • Tense blisters atop lesions of LP, or development of vesicle a ichenoid drug eruptions have L de novo on uninvolved skin been associated with β-blockers, antimalarials, captopril, gold, peni- • Differentiate from bullous LP, where blisters in lesions cillamine, HCTZ, NSAIDs of longstanding LP as a result of intense lichenoid inflammation and extensive liquefaction degeneration of u TIP basal keratinocytes a ichenoid contact dermatitis L • Histologically like LP, with linear deposition of IgG and C3 at – color film developers, dental restorative materials, musk DE junction ambrette, nickel, aminoglyco- • Circulating IgG autoantibodies react to 180/200 kDa antigen sides, gold within BM zone Keratosis Lichenoides Chronica (Nekam Disease) • Violaceous papular and nodular lesions; hyperpigmented and hyperkeratotic, covered with gray scales • Often, linear and reticulate pattern on the dorsal hands and feet, extremities and buttocks • Very refractory to treatment LP and Malignant Transformation • Risk is very low to none at all • Risk increased by longstanding disease, erosive or atrophic types of LP, and tobacco use • Most common sites for malignant transformation are tongue, gingiva and buccal mucosa • Most patients developing SCC in cutaneous LP had a history of either arsenic or X-ray exposure Lichenoid Keratosis (Lichen Planus-like Keratosis) • Brown to red scaling papule or plaque found on sun-exposed skin of extremities • Histological features of LP with additional finding of parakeratosis • Frequently occur with solar lentigo, seborrheic keratosis, and actinic keratosis General Dermatology  91
  20. 20. Associated Conditions • Autoimmune chronic active hepatitis • Primary biliary cirrhosis • Postviral chronic active hepatitis • HCV in some populationsTreatment • Spontaneous remissions and exacerbations • Oral/Mucosal LP– replacement of gold or amalgam dental restorations • Topical high potency steroids for mucosal and limited cutaneous disease • Topical immunomodulators such as tacrolimus ointment for oral/genital disease • Topical anesthetics for oral pain • Intralesional TAC • Systemic steroids for refractory cases • PUVA photochemotherapy successful in generalized LP • Oral retinoidsCourse and Prognosis • Typically persists 1-2 years • May follow chronic, relapsing course • Spontaneous remission on average after 15 months • Lichen planopilaris most chronic and progressive with little potential for hair regrowth • Hypertrophic LP follows protracted unremitting course • Oral LP does not usually spontaneously regress4.9 ATOPIC DERMATITISClinical Features Major • Pruritus • Facial and extensor involvement in infants and children • Flexural lichenification in adults • Chronic or relapsing dermatitis • Personal/family history of atopy Associated Features • Xerosis • Cutaneous infection • Nonspecific dermatitis of hands/feet • Ichthyosis, palmar hyperlinearity, keratosis pilaris • Pityriasis alba • Nipple eczema • White dermatographism and delayed blanch response • Anterior subcapsular cataracts, keratoconus • Elevated serum IgE levels • Positive immediate-type allergy skin tests • Early age of onset • Dennie-Morgan infraorbital folds92  2011/2012 Dermatology In-Review l Committed to Your Future
  21. 21. • Orbital darkening • Facial erythema or pallor • Perifollicular accentuation • Course influenced by environmental and/or emotional factorsGenetics • Stronger correlation between siblings than between siblings and parents • Exposure to environmental factors during childhood is likely to be the major factor • Seen in families with atopic dermatitis, asthma, and allergic rhinitis • Filaggrin gene mutations are known risk factorClinical Manifestations • Typically begins in infancy → 50% in first year of life, and an additional 30% between 1 and 5 years • Most children with AD eventually develop allergic rhinitis or asthma later in childhood Infancy • AD generally more acute and primarily involves the face, scalp, and the extensor surfaces of the extremities • Diaper area spared Older Children • Patient develops the chronic form of AD with lichenification and localization of the rash to the flexural folds of the extremities • Subsides as patient grows older, leaving adult with skin that is prone to itching and inflammation • Chronic hand eczema may be the primary manifestation of adults with ADComplications Ocular Problems • Eyelid dermatitis and blepharitis • Atopic keratoconjunctivitis • Keratoconus: conical deformity of cornea • Cataracts Infections • Frequently complicated by recurrent skin infections: u TIP – Kaposi’s varicelliform eruption → herpes simplex → results in annate antimicrobial peptides I eczema herpeticum → incubation of 5-12 days, multiple, itchy, include human β-defensin (HBD) and cathelicidins, such vesiculopustular lesions erupt in a disseminated pattern → as LL 37. Ong et al found a often become hemorrhagic and crusted deficiency of HBD-2 and LL – Molluscum contagiosum 37 in lesions from patients with atopic dermatitis com- – HPV pared to those with psoriasis. – Superficial fungal infections—Trichophyton rubrum and This decreased expression of Pityrosporum ovale innate antimicrobial peptides – S. aureus – found in over 90% of AD skin lesions. Honey may explain the increased sus-  ceptibility to colonization and colored crusting, folliculitis, and pyoderma are indicators of skin infection with S. aureus in secondary bacterial skin infection. Regional lymphadenopathy patients with atopic dermatitis4 common. Deep-seated S. aureus infections may indicate hyper-IgE syndrome General Dermatology  93
  22. 22. Foods • Food allergens exacerbate skin rashes in at least a subset of patients with AD, particularly infants and young children • Eggs, milk, peanuts, soybeans, tree nuts, fish, and wheat are the most common allergens implicated in AD • Following positive oral food challenges in children with AD, histamine concentration increases in the plasma  • Most AD patients do NOT have food allergyImmunohistochemistry • Lymphocytes are CD3+, CD4+, and CD45RO+ memory T helper cells • Langerhans cells and macrophages infiltrating into AD skin lesions have surface-bound IgE • Activated eosinophils are present in significantly greater numbers in chronic as compared to acute AD lesions Immunologic Abnormalities in AD • Increased synthesis of IgE • Increased expression of CD23 (low affinity IgE receptor) on B cells and monocytes • Increased basophil histamine release • Impaired DTH response • Decreased CD8 suppressor/cytotoxic T-cell number and function • Increased secretion of IL-4 and IL-5 by TH2 cells • Decreased secretion IFN-gamma by TH1 cells An Immunologic Aside • TH1 cells → produce IL-2, IFN-γ, and TNF-β, associated with cell-mediated immunity • TH2 cells → produce IL-4, IL-5, IL-6, IL-10, and IL-13, associated with antibody mediated immune responsesManagement Allergens • Dust mites, molds, animal dander, pollens • Avoidance of triggering foods • Infants and young children more likely to have food allergies; older children and adults sensitive to environmental aeroallergens Infectious Agents • Anti-staphylococcal antibiotics helpful in those colonized • HSV: Antiviral treatment very important to prevent disseminated disease; IV treatment may be necessary for disseminated eczema herpeticum • Molluscum contagiosum → topical imiquimod, liquid nitrogen, topical salicylic acid, or no therapy Pruritus • Antihistamines → use sedating antihistamine at night Systemic Glucocorticoids • Rarely indicated, and risk of rebound flare after discontinuation • Short courses can be done while other modalities are started, and tapering dosage is critical94  2011/2012 Dermatology In-Review l Committed to Your Future
  23. 23. UV Phototherapy • UVB useful adjunct to treatment of chronic recalcitrant AD • High intensity UVA can be fast-acting and effective with acute exacerbations of AD Systemic Cyclosporine or Tacrolimus • Oral cyclosporine or tacrolimus can help severe AD that is refractory to topical steroids • Discontinuation of treatment may result in rapid relapse of skin disease Probiotics • The utility of probiotics in primary prevention of atopic dermatitis has been studied • Lactobacillus GG cultures were given to pregnant women with a history of atopy to assess the effect of potentially beneficial gut flora on the prevention of atopic disease in their children • Frequency of atopic dermatitis in the probiotic group was half that in the placebo group at two years of lifePrognosis • Disease more severe and persistent in young children • Periods of remission grow longer as patient ages • Mild disease at infancy: Spontaneous resolution occurs in 40% of patients after age 5 • Poor prognostic factors – Widespread AD in childhood – Associated allergic rhinitis or asthma – Family history of AD – Early age of onset4.10 Alopecia AreataGenetics • High frequency of family history, especially in patients with early onset (37%) • Twin concordance = 55% (identical twins)Immunologic Factors • Major associations: Vitiligo and thyroid disease (10%), with increased prevalence of antithyroid antibodies and thyroid microsomal antibodies in AA • Other autoimmune diseases shown to be associated: pernicious anemia, diabetes, LE, myasthenia gravis, RA, polymyalgia rheumatica, ulcerative colitisEmotional Stress • May be precipitating factor in some casesClinical Features u TIP a ATTERNS of alopecia areata: patchy (most common); • Prevalence: 0.1-0.2%, with lifetime risk of 1.7% P reticulated; ophiasis (parietal/temporal/occipital); • Affects men and women equally ophiasis inversus (sisapho – bandlike pattern in fronto • 60% present before age 20 parietotemporal scalp); diffuse • Pull test may be positive at margins, indicating early disease • Usually asymptomatic, but some patients perceive pruritus, tenderness, burning, or pain preceding hair loss • Areata – partial loss of scalp hair General Dermatology  95
  24. 24. • Totalis – total loss of scalp hair • Universalis – 100% loss on scalp, eyebrows, eyelashes, and rest of body • Initial regrowth is white, followed by repigmentation • Nail dystrophy (10-66%), seen in one, some, or all nails, preceding, coinciding, or occurring after hair disease → pitting with irregular pattern or in organized rows; trachyonychia: longitudinal striations resulting in sandpaper appearance; Beau’s lines; onychorrhexis; thinning or thickening; koilonychia; red-spotted lunula; punctate or transverse leukonychiaPrognosis • Unpredictable course and pattern • Most patients see complete regrowth within one year without treatment • 10% develop severe chronic form • Predictors for poor prognosis: atopic dermatitis, childhood onset, widespread involvement, ophiasis, duration for longer than five years, onychodystrophyTreatment • All local treatments help treated areas, but do not prevent further spread • Spontaneous recovery is extremely common, with most showing regrowth within 1 year • First line: IL steroids concentration of 5 mg/cc maximum of 3 cc per visit → 0.1 cc per site, approximately 1 cm apart; after 6 months and no response, d/c • Topical steroids as monotherapy generally ineffective • Minoxidil 5%: stimulates follicular DNA synthesis and regulates hair physiology independently of blood flow influences; effective with alopecia areata involving 20-99% involvement in 25-50% of patients → initial hair regrowth in 12 weeks • Anthralin 0.25-1.0% • Squaric acid dibutyl or DNCB or DPCP (diphenylcyclopropenone) – aim is to maintain low- grade tolerable erythema, scaling, and pruritus, with weekly applications • PUVA, with either topical or systemic psoralen therapy; relapse after discontinuation occurs • Cyclosporine works, but systemic use associated with adverse effects and high recurrence rate4.11 Alopecia: Other Forms u TIPTrichotillomania a iopsy shows high B • Practice of plucking or breaking hair from the scalp or eyelashes number of catagen • Areas of alopecia characteristically contain hairs of varying length hairs, pigmentary defects and casts, • Girls under age of 10 trichomalacia, and • Treat with psychotherapy and antidepressant hemorrhageHot Comb Alopecia • African American women who straightened their hair with hot combs • Characteristically on the crown and spreads peripherally to form a large oval area of partial hair loss • Thermal damage to follicle by hot petrolatum, leading to destruction of hair follicle and follicular scar • May be same as follicular degeneration syndrome/central centrifugal scarring alopecia96  2011/2012 Dermatology In-Review l Committed to Your Future
  25. 25. Pseudopelade of Brocq • Scarring alopecia where destruction of the hair follicle produces multiple round, oval, or irregularly shaped cicatricial patches of varying sizes • No pustules, crusts, or broken-off hairs are present • Onset is insidious • Female:male = 3:1 • Alopecia permanent • No inflammation with decreased or absent sebaceous glands, normal or atrophic epidermisTraction Alopecia • Prolonged tension on the hair from braiding, ponytails, rolling curlers, twisting with fingersPressure Alopecia • Occipital areas of babies lying on their backs • In adults, prolonged pressure on the scalp during general anesthesia or after prolonged bedrest • People with chronic illness after prolonged bed rest in one position • Likely related to pressure-induced ischemiaLoose Anagen Syndrome • Anagen hairs pulled from the scalp with little effort • Blonde girls • Usually improves with ageFollicular Mucinosis • Deposition of mucin in the outer root sheath and sebaceous glands • Most commonly on scalp and beard area • Secondary type associated with CTCL with widespread and chronic lesions, and patients are olderMeralgia Paresthetica • May have alopecia of the anesthetic area of the outer thighHypothyroidism • Hair coarse, dry, brittle, and sparse • Telogen hairs 3x more prevalentHyperthyroidism • Hair becomes extremely fine and sparseAlopecia Neoplastica • Hair loss from metastatic tumors • Usually breast carcinoma General Dermatology  97
  26. 26. 4.12 Vitiligo • Half of all cases begin before age 20 • Depigmented white patches surrounded by normal or hyperpigmented border • Trichrome vitiligo: intermediate tan zones halfway between the normal skin color and the depigmentation • Hairs in vitiliginous areas become whiteFour Types 1.) Localized or focal (includes segmental) 2.) Generalized (most common) 3.) Universal 4.) AcrofacialGeneralized • Symmetrical • Face, upper chest, dorsal hands, axillae, groin • Skin around all orifices • Areas of trauma (knees and elbows)Focal • Asymmetric • Treatment resistant • 5% of adult, 20% of childhood cases of vitiligoUniversal • Entire body surface depigmentedAssociations • Insulin-dependent diabetes • Pernicious anemia • Hashimoto’s thyroiditis • Grave’s disease • Addison’s disease • Alopecia areataGenetics • Multifactorial • 30% of vitiligo patients have an affected relativeTreatment • Topical corticosteroids • Ultraviolet phototherapy (Narrow band UVB and Psoralen with UVA) • Laser (308 nm excimer) • Topical tacrolimus • Re-pigmented surgery with punch minigrafts, dermoscopic dermal grafts98  2011/2012 Dermatology In-Review l Committed to Your Future
  27. 27. 4.13 Pityriasis rubra pilaris • Small follicular papules → salmon-orange to reddish-brown color, pinhead size, and topped with scaly plug • Yellowish pink scaling patches, often begins on scalp • Solid confluent palmoplantar hyperkeratosisProgresses to: • Sides of the neck and trunk • Extensor surfaces of the extremities • Any portion of the body can be affectedClinical Features • Involvement generally symmetrical and diffuse, with characteristic small islands of normal skin within the affected areas • Palms and soles will be hyperkeratotic with fissuring • Nails: dull, rough, thickened, brittle, and striated; may crack and break; no pittingTreatment • Topical keratolytics • Systemic retinoids • Vitamin A 500,000 units daily • Systemic steroids for short term management • Methotrexate • Azathioprine • Cyclosporine4.14 Lichen sclerosus • Presents from childhood to old age, and occurs in all races • Females predominate at all agesClinical • White, polygonal, and flat-topped papules or plaques surrounded by erythematous to violaceous halo • Later, lesions coalesce into large atrophic patches, becoming smooth, slightly wrinkled, and white • Bullae may arise in patches • Pruritus can be severe, especially in anogenital area, where erosions and fissuring can occur • In women, normal anatomic structures may be obliterated • Balanitis xerotica obliterans → male involvement of the glans penis; hemorrhage is common in the glans • Extragenital lesions most frequent on the upper back, chest, and breasts, and are usually asymptomatic • + KoebnerizationCancer Risk • Increased risk of genital SCC in both men and women • Lifetime risk for women less than 5% General Dermatology  99
  28. 28. Etiology • Autoimmune phenomenon, likely • 20% of both men and women have at least one autoimmune disease (vitiligo, alopecia areata, or thyroid disease), and a larger proportion have circulating antibodies • Trauma can induce lesions, and boys do better after circumcisionChildhood LS • Onset in childhood in 10-15% of cases • Girls outnumber boys 10:1 • Genital disease represents 90% of childhood LS • In girls: Symptoms include difficulty with defecation, dysuria, perineal pruritus, and perineal skin lesions • In boys: Phimosis is most common presenting sign • May resolve spontaneously, especially around puberty (50% of girls, after circumcision in boys)Treatment • Superpotent topical steroids twice daily to be tapered in either strength or frequency over time • Topical tacrolimus ointment or pimecrolimus cream, sometimes effective • Oral retinoids may work with anogenital lichen sclerosus in both men and women4.15 Granuloma annulareLocalized GA • Young adults • Lateral or dorsal surfaces of fingers, hands, elbows, feet, ankles • White, pink, flat-topped papules that spread peripherally • Never ulcerate and heal without scarring • 75% clear within 2 yearsGeneralized GA • Diabetes in 20% • Diffuse papules • May be pruritic or asymptomatic • Lasts three months to four yearsMacular GA • Flat or slightly palpable lesions over feet, ankles, and upper medial thighs • Small papules can be felt in some casesSubcutaneous GA • Most common in children • Often a history of trauma to area • Multiple lesions may be present • Generally asymptomaticPerforating GA • Dorsum of hands100  2011/2012 Dermatology In-Review l Committed to Your Future
  29. 29. • Papules with central keratotic core representing transepidermal elimination of the degenerated material in the center of GA lesions4.16 Hirsutism u TIPAndrogens in Women a rugs → Hirsutism without D Virilization/Defeminization • Dehydroepiandrosterone (DHEA), adrenal • Androstenedione–adrenal, ovary •  Phenytoin •  Minoxidil • Testosterone–ovary, adrenal, extraglandular conversion of •  Diazoxide androstenedione and dehydroepiandrosterone •  Cyclosporine – Adrenal androgen regulated by adrenocorticotropin •  Hexachlorobenzene – Ovarian androgen regulated by luteinizing hormone – The hair follicle requires conversion of testosterone to dihydrotestosterone for expression of androgen actionTumors → Rapid Onset of Hair Growth with or without Accompanying Virilization • Adrenal adenomas and carcinomas • Arrhenoblastoma • Kruckenberg tumors of ovaryPolycystic Ovarian Disease • Most common cause of ovarian hyperandrogenism • Manifestations: Hirsutism, amenorrhea, virilizationCongenital Adrenal Hyperplasia Congenital adrenal hyperplasia (defects in adrenal steroidogenesis) can occur at any point in life. • 21-hydroxylase deficiency • 11β-hydroxylase deficiency • 3β-hydroxysteroid dehydrogenase isomerase deficiency (3β-hsd)Idiopathic Hirsutism • Women with evidence of androgen excess but with normal menses, normal-sized ovaries, no evidence of tumors of adrenal or ovary, and normal adrenal function • Slight elevations of plasma androstenedione and testosterone commonSigns of Virilization Signs of virilization → correlates with androgen overproduction • Deepening of the voice • Temporal balding • Clitoromegaly • Increased muscle mass in the limb girdlesSigns of Cortisol Excess • Plethora • Central obesity • Striae • Dorsocervical/supraclavicular fat pads General Dermatology  101
  30. 30. Work-up • Pelvic exam: Search for palpable ovarian masses • Radiographic imaging of the pelvis/adrenal glands • Laboratory exam: DHEA 8000 ng/ml or serum testosterone 2 ng/ml suggest neoplasm • Plasma testosterone levels in the normal range are difficult to interpret → does not necessarily reflect the free or unbound levels of hormone under conditions when testosterone-binding globulin levels are either increased or decreased • Cushing syndrome, if suspected, should be evaluated with an overnight dexamethasone suppression test • Polycystic ovarian disease: Diagnosis from history and physical exam • Delayed onset adrenal hyperplasia: Short ACTH stimulation test and measurement of plasma 17-hydroxy-progesterone4.17 Amyloidosis • Beta-pleated sheet forms of various host-synthesized moleculesClassification 1.) Primary (often has skin findings) 2.) Secondary (rare skin manifestations) 3.) Primary localized 4.) Secondary cutaneous or tumor associated 5.) Familial syndromesPathology • PAS positive and diastase resistant • Congo-red positive • Purple with crystal violet • Positive with thioflavin T • Secondary systemic amyloid (aa) loses its birefringence after treatment with potassium permanganate, but primary and localized forms do not u TIPPrimary Systemic Amyloidosis arotein AL → derived from Ig P • Involves tongue, heart, GI tract, and skin light chains (lambda subtype); • Involves skin in 40% AL also found in nodular amyloidosis produced by a • Includes myeloma-associated amyloidosis plasmacytomaClinical • Shiny, smooth, firm, flat-topped papules of waxy color that coalesce into nodules or plaques • Commonly around nose, eyes, mouth, and mucocutaneous junctions •  Purpuric lesions result from amyloid infiltration of blood vessels; occurs after trauma (pinch purpura) • Glossitis → may lead to dysphagia; lateral aspects of tongue shows indentations from teeth • Bullous amyloidosis → subepidermal hemorrhagic bullae at areas of trauma • Carpal tunnel syndrome • RA-like arthropathy • Shoulder pad sign → enlarged deltoids • Cardiac arrythmias and chf cause death • Prognosis poor102  2011/2012 Dermatology In-Review l Committed to Your Future
  31. 31. Secondary Systemic Amyloidosis • Amyloid in the adrenals, liver, spleen, and kidney as a result of some chronic disease, such as TB, leprosy, Hodgkin’s, Behçet’s, rheumatoid arthritis, ulcerative colitis, schistosomiasis, or syphilis • Skin not involved u TIPPrimary Cutaneous Amyloidosis a A amyloid fibrils → derived from SAA protein, an A • Keratin is the protein component acute phase reactant • No amyloid around the blood vessels a A also seen in Muckle-Wells (renal amyloidosis, rti- A Macular Amyloidosis caria, fevers, limb pains, and deafness) and familial • Moderately pruritic, brown, rippled Mediterranean fever macules in interscapular region of the a ialysis-related amyloidosis: beta 2-microglobulin is the D back protein component altered by uremia → carpal tunnel • May have associated notalgia paresthetica syndrome, bone cysts, and spondyloarthropathy Lichen Amyloidosis • Bilateral shins • Type IIa MEN • Small, brown, discrete, scaly papules • Treat by reducing friction, occlusion, il steroidsNodular Amyloidosis • Single or multiple nodules on extremities, trunk, genitals, or face • Overlying epidermis may appear atrophic • Numerous plasma cells • AL typeSecondary Cutaneous Amyloidosis • Seen following PUVA therapy and in benign and malignant neoplasms: nonmelanoma skin cancers, seborrheic keratoses, trichoepitheliomas • Also, keratin-derived amyloidFamilial Syndromes Associated with Amyloidosis • Familial Mediterranean fever and Muckel-Wells syndrome → show AA protein • MEN IIa → keratin-derived amyloidFamilial Amyloidotic Polyneuropathy (fap) • Fap I and fap II → mutations in transthyretin • Fap III → apolipoprotein a-1 • Fap IV → gelsolin mutation General Dermatology  103
  32. 32. Table 4-2. AmyloidosisTypes Fibril Protein Other FeaturesSystemicPrimary AL (lambda λ chain) Involves tongue, heart, GI tract, and skin. Petechiae, purpura, waxy skin colored papules, alopecia, car- pal tunnel syndrome, neuropathy, arthropathSecondary AA Result of chronic disease: TB, leprosy, Hodgkin’s, RA, Reiter’s, syphilis No Skin involement Amyloid in the adrenals, liver, spleen, and kidneyLocalizedCutaneousMacular Altered Keratin Rippled brown macules in interscapular region on back, notalgia parestheticaLichen Altered Keratin Brown, scaly papules on bilateral shinsNodular AL chains Single or multiple nodules on extremities, genitals, trunk, or faceHereditaryFamilial AA AR, intermittent fevers, renal amyloidosis,Mediterranean peritonitis, pleurisyFever MEFV gene; marenostrin/pyrin proteinMuckle Wells AA AD, periodic attacks of urticaria, fever, deafness, renal amyloidosisHemodialysis β2 microglobulinAssoicationSenile B amyloid protein Senile or neuritic plaques, Alzheimer’s disease4.18 Calciphylaxis • Painful violaceous eschar-like plaques associated with soft tissue necrosis • Metastatic cutaneous calcification from increased parathyroid hormone (and increased calcium phosphate product) secondary to renal failure • Treatment: Phosphate binding agents, parathyroidectomy104  2011/2012 Dermatology In-Review l Committed to Your Future
  33. 33. 4.19 AngioedemaReview of the Complement System Classic Pathway • C1 binds to Fc fragment of IgM or IgG in immune complexes • C1q does the binding to immunoglobulin • C1s fragment digests C4 and C2, activating them into a C4b, 2a complex, creating C3 convertase, that activates C5 convertase → membrane attack complex Alternative Aathway • Less clear, but C3 activated by a C3-convertase complex consisting of C3b, bb • During inflammation, low levels of C3b bind factor b, that undergoes cleavage by factor d to generate C3b, bb → acts as a C3 convertase C1 Esterase Inhibitor • Protease inhibitor • Inhibits the catalytic subunits of first components of classical pathway (C1r and C1s), kallikrein, plasmin • In absence of C1 esterase inhibitor, activated C1 and plasmin generate activated C2 kinin • C2 kinin mediates angioedema Angioedema u TIP Type I: anherited (Quincke’s edema) (Normal C1q levels) I  • Occurs in setting of lymphoproliferative disease life • Detected in the first or second decade of (low-grade lymphoma, CLL, monoclonal gammo • Autosomal dominant pattern of inheriance pathy of undetermined significance, systemic • Serum C1q normal in inherited form amyloidosis) or rheumatologic illness, where idio • efect in synthesis and/or function of C1 D esterase inhibitor type/anti-idiotype immune complexes consume • ype I: Low amounts of normal C1 sterase T available C1q, and functionally and quantitatively inhibitor lower the amounts of C1 esterase inhibitor • ype II: Normal amounts of dysfuncional C1 T • Can also occur in setting of autoimmunity esterase inhibor directed against the C1 esterase protein aAcquired (Low C1q) • Important point: in both the inherited and • ffects adult or elderly with no family history A acquired forms levels of C2 and C4 are decreased • erum C1q decreased in acquired form S because of the uncontrolled actions of C1sClinical Presentation • Swelling of head, neck, and extremities • Abdominal symptoms • Upper airway symptoms • Recurrent symptoms, with intervening time of weeks to monthsTreatment • Androgen therapy: danazol or stanozolol → bring about dramatic decreases in frequency and severity of attacks • Glucocorticoids, but tapering results in relapse of symptoms • Therapy for underlying disease • Pretreatment with androgens prior to surgical procedures General Dermatology  105
  34. 34. Diagnosis • Screen with C3 and C4 levels → C4 low, C3 normal in angioedema • C1q level low in acquired, but normal in hereditary4.20 Carcinoid Syndrome and Flushing DisordersMenopausal Flushing • Perimenstrual flushing when estrogen levels low • Hot beverages and emotion can exacerbate • Pharmocologic menopause caused by drugs: danazol, tamoxifen, clomophene citrate, decapeptyl, leuprolide, and 4-hydroxyandrostenedione • Tubal ligation or any surgical loss of ovarian function • Clinical manifestations include drenching perspiration, waking episodes during the night, prodromal sensation of overheating before the onset of flushing and sweating • Treat with oral estrogen replacement or clonidine hydrochloride 0.05 mg bidEmotional Flushing • Can treat with biofeedback, hypnosis, and nadolol (40-80 mg qd)Foods • Monosodium glutamate • Scombroid group of fish (tuna and mackerel) • Spicy foodsMastocytosis • See separate section later in this chapterMedications • Nicotinamide, disulfiram, metronidazoleCarcinoid Syndrome • 4% with abdominal carcinoid tumors have the carcinoid syndrome • Presence of syndrome implies hepatic metastases, extraabdominal carcinoid tumor, or large enough tumor burden such that the liver cannot degrade the increased level of hormone • Tumors derived from enterochromaffin (Kulchitsky) cells • Appendix is most common site, followed by the ileum • Ileal tumors are the most common source of the classic carcinoid syndrome, and these tumors metastasize most frequently Clinical • Pellagra-like lesions caused by excessive utilization of tryptophan → hyperkeratosis, xerosis, scaling of legs, forearms, and trunk, angular cheilitis, and glossitis • Rosacea stigmata • Yellow-brown or brown-gray patches on the forehead, back, and wrists • Pruritus • Chronic watery diarrhea in 85% • Abdominal pain, constipation, nausea, vomiting, malabsorption, anorexia, weight loss, small bowel obstruction, and rectal bleeding • Respiratory symptoms of wheezing, stridor, dyspnea, coughing, and bronchospasm106  2011/2012 Dermatology In-Review l Committed to Your Future
  35. 35. • Arthritis, psychiatric symptoms, osteoblastic bone lesions • Fibrotic reactions affecting the valves of the heart Diagnosis • Serotonin overproduction  • Elevated urinary 5-HIAA • Foods and drugs can affect the urinary excretion of 5-HIAA4.21 Lupus ErythematosusClassification Chronic Cutaneous LE • Discoid • Verrucous (hypertrophic) • LE-LP overlap • Chilblain • Lupus Panniculitis Subacute Cutaneous LE • Papulosquamous • Annular • Neonatal • Complement deficiency syndromes Acute Cutaneous LE • Systemic LE with skin lesions → localized or generalized erythema with bullaeDiscoid Lupus • Young adults, women:men 2:1 • Dull red macules with adherent scales extending into patulous follicles • Plugged follicles • Patches heal with atrophy, scarring, dyspigmentation, and telangiectasia Localized • Above neck: scalp, nose, malar, lips, ears • Pruritus and tenderness common • Mucosal involvement of mouth, nose, eyes, vulva common Generalized • Less common than localized • Thorax and upper extremities, in addition to usual sites above the neck • Elevated ESR, positive ANA, or leukopenia more common Course • 95% of cases confined to the skin at outset will remain so • Abnormal labs such as ANA, leukopenia, hematuria, or albuminuria identify those who progress; also, rash above and below the neck • Relapses are common • BCC or SCC occur in scars, and a favored site is the lower lip General Dermatology  107
  36. 36. Treatment • Sun avoidance • Avoid exposure to heat, cold, trauma • Topical corticosteroids (potent) with or without occlusion • IL steroids Antimalarials • First hydroxychloroquine (Plaquenil), then chloroquine, or add quinacrine • Side effects: erythema multiforme, purpura, urticaria, ocular risks are very small, nausea, vomiting, tinnitus, abducens nerve paralysis, toxic psychoses, leukopenia, and thrombocytopenia • Exacerbate PCT • Bleach hair • Quinacrine yellows hair and conjunctivae become yellowOther Forms of Cutaneous LE Verrucous LE (Hypertrophic) • Non-pruritic, papulo-nodular lesions on arms and hands • Resembles KA’s or LP • Treat with IL TAC LE-LP Overlap Syndrome • See LP section Chilblain Lupus Erythematosus • Chronic, unremitting form with lesions on fingertips, ears, calves, and heels • Lesions are due to cold • Treatment is the same as LE LE Panniculitis • Deep dermal and subcutaneous nodules, rubbery-firm, sharply defined, and nontender • Head, face, upper arms, chest, buttocks, thighs • Chronic, in women 20-45 years old • DLE at other sites, commonly • Heals with atrophy and deep depressions • Treat with antimalarials for many months Subacute Cutaneous Lupus • Scaly papules that evolve into either psoriasiform or polycyclic annular lesions (more commonly) • Telangiectasia and dyspigmentation always present • No follicular involvement • No scarring • Occurs on sun-exposed surfaces of face and neck, inner arms, axillae and flanks • Spares knuckles • Photosensitivity in 40% u TIP • Hard palate involved in 40% a ajority positive for anti-Ro M • Concomitant DLE in 20% a rugs that may induce: HCTZ, D • At least half of the patients meet ARA criteria of SLE enicillamine, glyburide, griseofulvin, piroxicam, spironolactone, diltiazem, (usually have arthralgia, arthritis, leukopenia, positive ANA) ACE inhibitors, terbinafine • Disease runs a mild course108  2011/2012 Dermatology In-Review l Committed to Your Future
  37. 37. Neonatal LE • Annular scaling erythematous macules and plaques on head and extremities within the first few months of life in babies born to mothers with LE, rheumatic disease, or other connective tissue disorders • 50% mothers asymptomatic at delivery • Lesions resolve spontaneously by 6 months, healing without scarring • Photosensitivity may be prominent u TIP • 75% of cases involve girls a 0% have congenital heart 5 • Thrombocytopenia and hepatic disease as frequent as cardiac block, which is permanent (this may be the only manifestation disease of disease)Complement Deficiency Syndromes • Most commonly C2 and C4 • Photosensitivity • Annular scle lesions • Ro antibody formationSystemic LE Criteria: 4 Needed • Malar erythema • Discoid LE • Photosensitivity • Oral ulcers • Nonerosive arthritis • Serositis (carditis or pleurisy) • Nephropathy • CNS disorder (seizure or psychosis) • Hematologic disorder • Immunologic disorder (positive LE cell preparation, anti-DNA or Sm, false-positive RPR) • Positive ANA Cutaneous manifestations • Butterfly facial erythema, may be associated with edema → lasts days to weeks and heals without scarring • Bullous lesions, sun-exposed areas → histologically like EBA with antibodies against collagen Type VII, but responds to dapsone (EBA does not) • Fingertips and toetips show puffy erythema, telangiectasias • Periungual telangiectasias • Red lunulae • Erythematous to purplish palms and soles • Telangiectasias on face or elsewhere • Diffuse nonscarring hair loss with short, broken-off hairs in frontal region • Multiple (15) dermatofibromas • Vasculitis secondary to antiphospholipid antibody • Cryoglobulinemia, livedo reticularis, thrombophlebitis, cutaneous infarction • Erythema multiforme-like lesions (Rowell’s syndrome) • Calcinosis cutis • Plaque-like depositions of mucin General Dermatology  109
  38. 38. Pregnancy and SLE • Miscarriages occur with greater frequency • LE may worsen, or go into remission during pregnancy • Fetal death risk increased with anti-cardiolipin or anti-Ro antibodies • Postpartum period shows the highest risk to the patientDrug-induced LE • Usually benign course u TIP • Hydralazine → 14%, with slow acetylators (HLA-DR4) a Hydralazine, procainamide, sulfon- more prone amides, penicillin, anticonvulsants, • Procainamide → 50% of treated patients minocycline, and INH • Anti-histone antibody closely associated with symptomatic a rug-induced LE not usually D disease associated with skin, renal, and CNS manifestations • Penicillamine induces native disease, with anti-dsDNA Ab’s • HCTZ induces SCLE4.22 Scleroderma Chronic disease of unknown etiology affecting the microvasculature and loose connective tissue.Classification Localized Scleroderma • Morphea → most common type • Generalized morphea → morphea, symmetric and bilateral lesions; but absence of Raynaud’s, acrosclerosis, and organ involvement differentiates from SSc • Guttate morphea (LSA) • Nodular morphea • Subcutaneous morphea (morphea profunda) • Linear scleroderma → bandlike lesions that may involve the deeper layers of the skin Systemic Sclerosis • Limited (lSSc): 60%, includes CREST syndrome; 70-80% have anti-centromere antibodies and systemic involvement may not appear for years; patients are older than dSSc and many outlive the disease; better survival rate (50% at 12 years) • Diffuse (dSSc): Abrupt onset of swelling of the hands and feet with Raynaud’s and hidebound changes in the skin; polyarticular symmetric synovitis, tenosynovitis and tendon friction rubs often present; nail fold capillary dilatation and destruction  • arly onset of internal organ involvement; anti-topoisomerase 1 antibodies (SCL-  E 70) in 30%; worse survival rate (15% at 12 years)Epidemiology Localized Scleroderma • Women:men 3:1 • More common in whites Systemic Sclerosis • Women:men 4:1 • More common in black women, with diffuse disease more likely to affect black women • 7-year survival 75%110  2011/2012 Dermatology In-Review l Committed to Your Future

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