Chronic Blistering Dermatoses

Chronic Blistering Dermatoses Part 2
By:David M. Bracciano, D.O.

Pregnancy- Related Dermatoses
* Intrahepatic Cholestasis of Pregnancy
* Polymorphic Eruption of Pregnancy
* Herpes (pemphigoid) gestationis
* purity Urticarial Papules and Plaques of Pregnancy (PUPPP)
* Papular Dermatitis of Pregnancy
* purity Folliculitis of Pregnancy

Intrahepatic Cholestasis of Pregnancy
* Generalized purities and jaundice
* No primary skin lesions, secondary excoriations
* Caused by cholestasis, occurs late in pregnancy, resolves after delivery
* 0.5% of pregnancies
* Tx; oral steroids

Polymorphic Eruption of Pregnancy
* Classification of all purity inflammatory dermatoses of pregnancy:
* Toxemic rash of pregnancy
* Pruigo annularis
* EM gestationis
* PUPPP
* purity Folliculitis of Pregnancy

Polymorphic Eruption of Pregnancy
* Pruritic inflammatory dermatoses of pregnancy occur in 1 of every 120 to 240
* Treatment and prognosis is similar in subtypes

Pruritic Urticarial Papules and Plaques of Pregnancy (PUPP)
* First reported in 1979
* Erythematous papules and plaques that begin as 1-2 mm lesions within the abdominal striae
* Spread over the course of a few days to involve the abdomen, buttocks, thighs
* Upper chest, face, and mucous membranes spared

PUPPP
* Lesions coalesce to form urticarial plaques
* Intense pruritis is characteristic
* Primigravidas 75% of the time, usually does not recur with subsequent pregnancies
* Begins late in third trimester and resolves with delivery
* May be associated with increase weight gain
* Histology: perivascular infiltrate in upper and mid dermis, epidermis normal
* Tx: topical or oral steroids

Papular Dermatitis of Pregnancy
* Pruritic generalized eruption of 3-5 mm erythematous papule surmounted by a small, firm, central crust
* May erupt at any time during pregnancy and resolve with delivery
* Marked elevation of urine HCG
* Tx; oral steroids, may recur in subsequent pregnancies

Prurigo Gestationis (Besnier)
* purity, excoriated papules of the proximal limbs and upper trunk
* Onset is 20-34 weeks gestation
* Clears in postpartum period and does not recur
* Tx: topical steroids

Pruritic Folliculitis of Pregnancy
* 2nd or 3rd trimester
* Small follicular pustules scattered widely over the trunk
* May be a type of hormonally induced acne

Impetigo Herpetiformis
* Form of severe pustular psoriasis occurring in pregnancy
* Acute, usually febrile onset of grouped pustules on an erythematous base
* Begins in the groin, axillae, and neck
* Increased WBC, hypocalcemia
* Recurs with pregnancy, fetal death due to placental insufficiency
* Tx; prednisone 1mg/kg

Cicatricial Pemphigoid (Benign Mucosal Pemphigoid)
* Vesicles which quickly rupture, leaving erosions and ulcers with scarring
* Primarily occur on mucous membranes, conjunctiva (66%) and oral mucosa (90%)
* Oral mucosa may be the only affected site for years; desquamative gingivitis of buccal mucosa
Cicatricial Pemphigoid
* Tends to affect middle-aged to elderly women 2:1 female/male
* Ddx; oral lichen planus (biopsy and IF)
* Chronic disease that may lead to slowly progressive shrinkage of the ocular mucous membranes and blindness
* Also occurs in pharynx, esophagus, larynx, nose, penis, vagina, anal mucosa, deafness
* Cutaneous lesions in 25%; tense bullae
* Bullae heal with or without scarring, occur on the face, scalp, neck, and inguinal region and extremities
* Some pts may have antibodies targeted against classic bullous pemphigoid antigens and should be classified as “mucosal predominate bullous pemphigoid”
* Chronic course, pts health not usually affected
* IgA antibodies may explain mucosal scarring tendency
* Little tendency to remission (unlike bullous pemphigoid)
* Subtypes include types that target basement membrane zone antigens (laminin, glycoproteins, )
* Direct IF testing C3 and IgG at the lamina lucida in 80-95%
* Tx: mild cases topical steroids (Temovate/Orabase), intralesional triamcinolone every 2-4 weeks
* Tx: Dapsone, prednisone, Azathioprine or cyclophosphamide

Epidermolysis Bullosa Acquisita
* Antibodies to Type VII collagen
* Skin fragility, healing with scars
* Bullous eruption, scaring, milia
* Need to exclude all other bullous diseases: porphyria cutanea tarda, pemphigoid, pemphigus, dermatitis herpetiformis, and bullous drug eruption

Epidermolysis Bullosa Acquisita
* Tx; unsatisfactory, steroids, dapsone, colchicine, IV Immunoglobulin, Cyclosporin

Dermatitis Herpetiformis
* Chronic, relapsing, severely purity disease
* Grouped symmetrical, polymorphous, erythematous-based lesions
* May be papular, papulovesicular, vesiculobullous, bullous, or urticarial
* Itching and burning are intense
* Spontaneous remissions lasting a week

Dermatitis Herpetiformis
* Eruption usually symmetrical
* Scalp, nuchal area, posterior axillary folds, sacral region, buttocks, knees, forearms
* Pruriginous papules are a common feature
* Vesicles are more common than bullae; however all types of these lesions may be present in one patient
* Course of the disease is generally lifelong, with prolonged remissions being rare

Dermatitis Herpetiformis
* Very few patients with DH ever have diarrhea although DH is associated with Gluten-sensitive-enteropathy (GSE)
* 87% of pts with DH and IgA deposits in the skin are HLA-B8 positive (like GSE)
* Gluten is a protein found in cereals except for rice, oats, and corn
* IgA antibodies are formed in the jejunum, may deposit in the skin
* Associated with; Thyroid disorders, small bowel lymphoma, non-Hodgkins lymphoma
* 70% of pts have abnormalities of the jejunal mucosa
* Gluten-free diet decreases Dapsone dose requirements after 3-4 months
* Ddx: pemphigoid, EM, scabies, contact dermatitis, atopic dermatitis, eczema, insect bites, pruigo nodularis
* IgA in a granular pattern in the dermal papillae in normal skin is specific and pathognomonic for DH
* IgA deposits may be focal, so multiple biopsies may be needed.
* Deposits of the antibody are more often seen in previously involved skin or normal appearing skin adjacent to involved skin
* Equal male:female
* Onset between 20 to 40 years
* Tx: Dapsone 50-300mg daily (hemolytic anemia, methemoglobinemia, check G6PD prior to tx) monitor Hct,WBCs, LFTs
* Tx: Sulfapyridine 0.5g QID to 2-4g/day
* Gluten-free diet will decrease need for meds or allow pt to go off them Celiac Society

Linear IgA Bullous Dermatosis
* Subepidermal blisters, a neutrophillic infiltrate, circulating IGA antibasement membrane zone antibody
* Deposition of IgA antibody at the dermoepidermal junction by direct IF

Linear IgA Bullous Dermatosis Adult Form
* Acquired autoimmune blistering disease
* Clinical pattern similar to dermatitis herpetiformis, or with vesicles and bullae in a bullous pemphigoid-like appearance
* 50% mucous membrane involvement
* Oral and conjunctival lesions may be scarring
* No association with enteropathy or with HLA-B8
* Tends to remit over several years

Linear IgA Bullous Dermatosis Adult Form
* Linear IgA dermatosis can occur as a drug-induced disease:
* Self-limited, less mucosal involvement, usually does not have circulating autoantibody
* IgA is usually deposited in the subbasal lamina area
* Vanco, Lithium, amiodarone, captopril, PCN, lasix, dilantin, and others
* Histo: papillary dermal microabscess with neutrophils, subepidermal bullae may be seen with neutrophils and eosinophils
* Direct IF: homogeneous linear deposition of IgA is present at the BMZ
* Indirect IF: few will have circulating IgA autoantibody with anti-BMZ specificity
* Tx: Dapsone, topical steroids

Linear IgA Bullous Dermatosis Childhood Form
* Chronic Bullous Disease of Childhood: acquired, self-limited bullous disease
* Onset by 2 or 3, remits by age 13
* Bullae develop on erythematous or normal appearing skin
* Trunk, buttocks, genitalia, and thighs
* Perioral and scalp lesions are common, oral lesions not uncommon
* Bullae arranged in a rosette or annular array “cluster of jewels”
* Histo: subepidermal bullae filled with neutrophils, eosinophils may predominate
* Direct IF: linear deposition of IgA at the BMZ
* Indirect IF: positive for circulating IgA antibodies in 50%
* Tx: Sulfapyridine or dapsone, topical steroids

Transient Acantholytic Dermatosis
* Over age 50, fragile vesicles, limited extent, sparse, limited duration
* Rapid crusting, keratotic erosion <1cm
* Usually chest, shoulder
* Direct IF is negative
* Tx: topical steroids, isotretinoin

Nutritional Diseases
* Caused by insufficiency or excess of dietary essentials
* Common in underdeveloped countries, infants and children
* Often pts have features of several disorders if diet is generally restricted
* Alcoholism is the main cause in developed countries
* Postoperative pts, psychiatric pts (anorexia nervosa, bulimia), surgical or inflammatory bowel dysfunction, Crohn’s

Hypovitaminosis A (Phrynoderma)
* Vitamin A: fat soluble found in milk, fish oil, liver, eggs, and as carotenoids in plants
* Common in children in developing world
* Developed countries found in diseases of fat malabsorption; Crohn’s, celiac, cystic fibrosis, cholestatic liver disease
* Vitamin A required for keratinization of mucosal surfaces
* Abnormal keratinization leads to increased mortality from inflammatory disease of the gut and lung ie; diarrhea and pneumonia
* Phrynoderma or “toadskin” resembles keratosis pilaris.
* Keratotic papules over extremities and shoulders arising from pilosebaceous follicles
* Eruption begins on thighs or upper arms. Spreads to shoulders, abdomen, back, and buttocks, face and neck
* Skin displays dryness and scaling

Hypovitaminosis A Ocular Findings
* Major cause of blindness in children in the developing world!
* Earliest finding is delayed adaptation to the dark (nyctalopia)
* Night blindness, xeropthalmia, xerosis corneae, keratomalacia
* Bitot’s Spots; circumscribed areas of xerosis of the conjuctiva lateral to the cornea

Hypovitaminosis A
* Diagnosis: based on eye findings, serum Vitamin A level.
* Tx: 300,000 IU Vitamin A

* Skin findings similar to side effects of Retinoid therapy. Children are at greater risk.
* Loss of hair and coarseness, loss of eyebrows, exfoliation and pigmentation of skin, clubbing, hepatosplenomegaly, anemia, increased LFTs, pseudotumor cerebri with papilledema

Hypervitaminosis A Adults
* Early signs are dryness of the lips and anorexia. Followed by bone and joint pains, follicular hyperkeratosis, branny desquamation of the skin, loss of scalp hair and eyebrows, dystrophy of the nails.
* Fatigue, myalgia, depression, anorexia, liver disease
* Birth defects with excess Vit A in pregnancy

Vitamin D
* Deficiency of Vitamin D causes alopecia, osteomalacia
* Vitamin D overdose can cause hypercalcemia and calcinosis.

Vitamin E Deficiency
* Most common in infants of low birth weight
* Peripheral edema, progressive neuromyopathy, and ophthalmoplegia

Vitamin K Deficiency
* Dietary deficiency of vitamin K, a fat soluble vitamin, does not occur in adults because it is synthesized by bacteria in the large intestine
* Liver disease causes deficiency
* Drugs: coumadin, salicylates, cholestyramine
* Decrease in the vitamin K-dependent clotting factor II, VII, IX, and X.
* Purpura, hemorrhage, and ecchymosis.
* Tx: 5 to 10 mg/day IM Vit K for 2-3 days

Vitamin B1 Deficiency
* Thiamine deficiency results in Beriberi
* Edema, and peripheral neuropathy

Vitamin B2 Deficiency
* Riboflavin deficiency is seen most often in alcoholics.
* Phototherapy for neonatal icterus, boric acid ingestion, hypothyroidism, chlorpromazine
* Oral-ocular-genital Syndrome: angular chelitis, atrophic tongue, photophobia, blepharitis, confluent dermatitis of scrotum
* Tx: 5mg Riboflavin qd

Vitamin B6- Pyridoxine
* Deficiency: occurs in uremia and cirrhosis
* Seborrheic dermatitis, glossitis, chelitis, conjunctivitis, confusion, neuropathy
* Excess: subepidermal vesicular dermatosis, peripheral sensory neuropathy

Vitamin B12 Deficiency Cyanocobalamin
* Absorbed through the distal ileum after binding to gastric intrinsic factor in an acid ph.
* Deficiency caused by: decreased intrinsic factor, achlorhydria, malabsorption syndromes (pancreatic, sprue)
* Because of large body stores in adults, deficiency occurs 3 to 6 years after onset of GI disease!
* Glossitis, hyperpigmentation accentuated in exposed areas resembling Addison’s disease
* Megaloblastic anemia, weakness, paresthesias, ataxia
* Tx: IM B12, neuro defects may not improve

Folic Acid Deficiency
* Diffuse hyperpigmentation, glossitis, chelitis, and megaloblastic anemia

Scurvy Vitamin C Deficiency
* Most common vitamin deficiency dxd by dermalologists
* Elderly alcoholics and psychiatric pts

Scurvy “The Four H’s”
* Hemorrhagic signs
* Hyperkeratosis of the hair follicles
* Hypochondriasis
* Hematologic abnormalities
* Perifollicular petechiae and ecchymoses, subungual, subconjunctival, intramuscular, and intraarticular hemorrhage
* “Corkscrew hairs”; hairshafts are curled in follicles capped by keratotic plugs
* Hemorrhagic gingivitis; bleeding gums, epistaxsis, anemia
* Dx: serum ascorbic acid level
* Tx: ascorbic acid 800-1000mg qd x 1 week

Niacin Deficiency Pellagra
* Nicotinic acid, vitamin B3, niacin or its precursor tryptophan is associated with a diet entirely composed of corn, millet or sorghum
* Other vitamin defficiencies or malnutrition coexist
* Most cases are alcoholics in developed countries

Pellegra Causes
* Carcinoid tumors, which divert tryptophan to serotonin
* Intestinal parasites esp; hookworm
* GI diseases ie; Chron’s
* IV alimentation
* Anorexia nervosa
* Meds; Isoniazid, azathioprine, 5-FU, Hydantoins

Pelegra
* Chronic disease affecting GI tract, CNS, skin
* “3 D’s”; diarrhea, dementia, dermatitis
* Dermatitis: photosensative eruption, perineal lesions, thickening and pigmentation over boney prominences, seborrheic dermatitis-like eruption on face

* Photosensitive eruption on face, neck, chest
* (Casal’s necklace), eruption may be vesicular or bullous (wet pellegra)
* After several phototoxic events the skin shows hyperpigmentation, scaling, a copper hue
* Scrotal and perineal erosions, fissures, angular chelitis
* CNS and GI symptoms may occur without skin changes; apathy, muscle weakness, parasthesias, dizziness, psychosis
* Disease is progressive, majority of pts die in 4-5 years if untreated

Pellegra Diagnosis and Treatment
* Diet: Animal protiens, eggs, milk, vegetables
* 100mg nicotinamide qid
* Skin lesions begin to resolve within 24 hours of tx

Biotin Deficiency
* Biotin is universally available and is produced by intestinal bacteria
* Deficiency is rare, can occur in short gut or malabsorption
* Dermatitis is perioral; pathcy, red, eroded lesions on the face and groin
* Candida overgrowth of lesions occurs
* Alopecia including loss of eyebrows and eyelashes
* Neuro: depression, lethargy, parasthesias
* Infants: hypotonia, lethagry seizures, developmental delays
* Inherited form: detecting organic aminoaciduria with 3-hydroxyisovaleric acid
* Tx: 10mg Biotin qd Skin lesions resolve rapidly, but neuro damage may be permenant

Zinc Deficiency
* Inherited or Aquired
* Inherited: Acrodermatitis enteropathica
* Premies at risk due to inadequate body zinc stores
* Weaning from breast from breast milk precipitates clinical zinc deficiency
* Parental nutrition without adequate zinc content may contribute

Zinc
* Acquired: alcoholics, bowel disease, anorexia, AIDS
* Zinc requirements increase with metabolic stress
* Diets containing mainly cereal grains are high in phytate, which binds zinc, Middle East, North Africa

Zinc Dermatitis
* Pustular and bullous, acral and perioral
* Patchy, red, dry, scaling with exudation and crusts. Angular chelitis and stomatitis
* Nail dystrophy, alopecia
* Diarrhea, growth retardation, CNS
* Histo: vacuolation of the keratinocytes of the upper stratum malpighii

Zinc Deficiency Diagnosis and Treatment
* Characteristic skin findings, acral or perioral dermatitis
* Chronic diaper rash with diarrhea in an infant should lead to evaluation for zinc deficiency
* Diagnosis: low serum zinc, alkaline phosphatase
* Tx: zinc sulfate 1-2 mg/kg/day
* Tx: acrodermatitis enteropathica is lifelong

Essential Fatty Acid Defficiency
* Lbw infants, bowel disease, alimentation
* Dermatitis similar to zinc def : xerosis, EFA’s constitute 25% of the fatty acids of the stratum corneum
* Widespread erythema, intertriginous weeping eruption, infection, alopecia
* Decrease in linoleic acid and an increase in palmitoleic and oleic acids
* Ratio of eicosatrienoic acid to arachidonic acid of >0.4 is diagnostic
* Tx: Intralipid 10% IV

Iron Deficiency
* Common in menstration
* Mucocutaneous; glossitis, angular chelitis, pruitus, telogen effluvium
* Plummer-Vinson syndrome: microcytic anemia, dysphagia, glossitis (middle aged women) thin lips, narrow mouth, koilonchia in 50%
* Post-cricoid esophageal web
* Diagnosis: serum iron (Fe+)
* Tx: iron sulfate 325 mg tid

Selenium Deficiency
* IV alimentation, poor soil selenium content, lbw infants
* Children: hypopigmentation of skin and hair (psuedoalbinism), leukonychia
* Cardiomyopathy, muscle pain, elevated muscle enzymes (cpk)
* Tx: 3 ug/kg/day selenium

Protein-energy Malnutrition
* Spectrum of diseases: marasmus, kwashiorkor, and marasmic kwashiorkor
* Endemic in developing world
* Marasmus; def of protein and calories, children < 60% of IBW without edema
* Kwashiorkor; protein def, 60-80% of IBW with edema or hypoproteinemia

Marasmus/ Kwashiorkor
* Cystic fibrosis, dietary restrictions
* Marasmus: skin is dry, wrinkled, loose
* “Monkey facies”; due to lose of buccal fat pad, no edema
* Kwashiorkor; edema, potbelly, hair and areas of skin are hypopigmented, hair is red, gray to white
* Africans call them “Red Children”
* “Flag Sign”; alternating bands of pale and dark hair along a single strand correspond to periods of good and poor nutrition
* “Mosaic skin”; areas of hyper/hypopigmentation resemble peeling paint

Carotenemia and Lycopenemia

* Excessive ingestion of : carots, oranges, squash, spinach, turnips, corn, beans, butter, eggs, pumpkins, sweet potatoes, papaya (seen in Kirksville)
* Yellowish discoloration of skin, palms, soles, central face
* Carotenemia occurs in vegitarians
* Lyconpenemia; red foods, beets, tomatoes, chili beans (flatulence), berries leads to reddish discoloration of skin aka “K.C. Chiefs’ syndrome


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Abnormalities In Dermal Connective Tissue

Abnormalities In Dermal Connective Tissue
By: Erik Austin, D.O., M.P.H.

Elastosis perforans serpiginosa – Serpiginous arrangement of confluent, keratotic papules on the arms, face/neck, legs

Keratotic papules of EPS
Typical site affected = neck
Elastosis perforans serpiginosa
EPS
* MC in young adults with a M:F ratio of 4:1
* Runs a variable course of 6 mos to 5 years with spontaneous resolution
* Associated with: Down Syndrome, Ehlers-Danlos, osteogenesis imperfecta, Marfan’s, Rothmund-Thomson, acrogeria, systemic sclerosis
* Tx = LN2, Penicillamine
* Annular plaques of EPS
* Atrophic scars often form
* Hyperelastic epidermis that clutches the increased dermal elastic fibers like a claw
* Transepidermal elimination of neutrophils and elastic fibers from the dermis through a channel in the epidermis

Reactive perforating collagenosis (RPC)
Keratotic papules on upper extremity, face or buttocks

Reactive perforating collagenosis
RPC
* Rare, familial, non-pruritic skin disorder
* Lesions begin in 2nd decade
* Involution occurs after 6-8 weeks, with new crops appearing for years
* May be a reaction to trauma
* Acquired form may be assoc. w/systemic dz
* TX = treat underlying disease

Pseudoxanthoma elasticum (PXE)
* Yellow papules, calcified plaques, sagging skin; chicken skin
* Inherited disorder of the skin, eyes, and cardiovascular system
* Has recessive and dominant inheritance
* Exaggerated nasolabial folds is characteristic
* Involvement of the cardiovascular system occurs with a propensity to hemorrhage

Mucosal lesions
* Retinal change = Angioid streaks; in up to 85%
* Mitral valve prolapse, 71% of 14 pts
* Young pt w/hypertension = r/o PXE
* Histo: mid-dermis w/elastic fibers that are swollen and granular - “raveled wool”
* No distinctive therapy
* Limit dietary calcium and phosphorus

Histopathology of PXE
* A. calcium deposits on elastic fibers in advanced PXE
* B. irregularly clumped elastic fibers, Verhoeff van Giesson

Perforating calcific elastosis
* Acquired, localized disorder
* Frequently found in obese, multiparous, middle-aged women
* Yellowish, lax, well circumscribed, reticulated or cobblestones plaques occur in the periumbilical region with keratotic papules
* Shares features with PXE, without systemic features
* Trauma of pregnancy, obesity or surgery promote elastic fiber degeneration
* No effective therapy

Ehlers-Danlos syndromes
* A group of genetically distinct disorders characterized by excessive stretchability and fragility of the skin
* Tendency toward easy scar formation, calcification of the skin to produce, pseudotumors, and hyperextensibility of the joints

Clinical features of Ehlers-Danlos syndrome
* Two types of growths seen with EDS
* Molluscum pseudotumor = a soft fleshy nodule seen in areas of trauma
* Spheroids = hard subcutaneous nodules that become calcified, ?Result of fat necrosis
* Types I, II, III and one subtype each of types of IV, VII and possibly VIII = AD
* One subtype of IV, VI, VII, and X = AR
* Type V = X-linked inheritance
* Treatment is supportive
* Avoidance of trauma

Marfan syndrome
* AD
* Skeletal, cardiovascular, and ocular involvement
* Important abnormalities include: tallness, loose-joints, a dolichocephalic skull, high arched palate, arachnodactyly, pigeon breast, pes planus, poor muscular tone, large deformed ears
* Ascending aortic aneurysm and mitral valve prolapse are commonly seen
* Ectopic lentis and striae
* Gene defect = chromosome 15
* Abnormal elastic tissue in fibrillin 1 and fibrillin 2

Cutis Laxa – loose, hanging skin – usually entire integument is involved
Cutis laxa (generalized elastosis)
* AD = primarily cutaneous, good prognosis
* AR = significant internal involvement, die young
* X-linked recessive = occipital horn syndrome
* Nonfamilial forms have been described
* May be associated with an underlying disease or inflammatory skin process
* Mid-dermal elastosis is an acquired, nonfamilial condition affecting primarily young women, cause unknown
* Tx = disappointing; surgery is unsuccessful

Cutis laxa (generalized elastosis)
* Premature aging, severe pulmonary emphysema, and fragmentation of dermal elastic fibers

Blepharochalasis
* Lax eyelid skin due to swelling of lids
* Uncommon
* AD
* Lack of elastic fibers, and abundant IgA deposits have been demonstrated
* Ascher Syndrome = progressive enlargement of the upper lip and blepharochalasis / treatment is surgical

Anetoderma (macular atrophy)
* A group of disorders characterized by looseness of the skin due to loss of elastic tissue
Anetoderma – macular atrophy and atrophic plaques – buttonhole sign. Typical location: trunk, arms, shoulders, thighs
* Anetoderma: decreased elastic fibers in the papillary and reticular dermis
Striae rubra, striae alba: depressed lines or bands

Striae distensae
* Can occur secondary to pregnancy or after sudden weight gain or muscle mass
* Associated with Cushing’s syndrome and
* Prolonged application of topical steroids
* Overtime striae become less noticeable
* Tx = topical tretinoin; vascular lasers

Linear focal elastosis (elastotic striae)
* Asymptomatic, palpable, striaelike yellow line of the middle and lower back
* Distinguished from striae in that there is no depression

Acrodermatitis chronica atrophicans
* Acquired diffuse thinning of the skin
* Reddish appearance on extensor surfaces
* Progresses to smooth , soft, atrophic skin
* Results from infection with Borrelia

Osteogenesis imperfecta
* Affects: bones, joints, eyes, ears, and skin
* types I-IV, I and IV = AD
* II and III = AD/AR
* 50% are type I
* type II is lethal within 1st week of life
* Brittle bones, fractures occur early in life, sometimes in utero
* Loose-jointedness and dislocations
* Blue sclera
* Deafness
* Thin skin; atrophic scars
* EPS has associated
* Defect is abnormal collagen synthesis, resulting in type I collagen of abnormal structure
* Major causes of death = respiratory failure and head trauma
* Type I and IV have a normal life span
* TX = Pamidronate

Homocystinuria
Inborn error in the metabolism if methionine
* Homocystine in the urine and CT abnormalities
* cystathionine synthetase deficient
* Genu valgum, kyphoscoliosis, pigeon breast, frequent fractures
* Facial skin has a characteristic flush
* Other skin is blotchy red
* Hair is fine, sparse and blonde
* Teeth are irregularly aligned
* Downward dislocations of lens
* TX = hydroxocobalamin and cyanocobalamin – variable results

ERRORS IN METABOLISM
SYSTEMIC AMYLOIDOSIS primary systemic amyloidosis
* Involves mesenchymal tissue, the tongue, heart, gastrointestinal, and skin
* Cutaneous manifestations in 40%
* Amyloid fibril proteins are composed of AL
* Derived from immunoglobulin light chains
* 90% will have fragment in urine and serum
* Waxy, firm, flat-topped or spherical papules
* Coalesce to form nodules and plaques
* Eyes, nose, mouth, and mucocutaneous junctions are commonly involved
* Purpuric lesions and ecchymosis (15%)
* Results from amyloid infiltration of vessels
* Glossitis with macroglossia (20%)
* May cause dysphagia
* Bullous disease is rare and scarring
* Subepidermal: DDx PCT and EBA
* Systemic findings: peripheral neuropathies, arthropathy, GI bleeding, cardiac disease
* Prognosis is poor, median survival 13 mos, 5 mos in myeloma associated cases
* Treatment is difficult = melphalen, prednisone, hematopoietic stem cell transplantation
* Macroglossia with dental impression of the tongue
* Periorbital ecchymosis, “raccoon sign”
Secondary systemic amyloidosis
* Amyloid involvement of adrenals, liver spleen, and kidney as a result of some chronic disease (TB, leprosy, etc.)
* Skin is not involved
* Amyloid fibrils are designated AA, protein component is unrelated to immunoglobulin
* Treat the underlying condition

CUTANEOUS AMYLOIDOSIS primary cutaneous amyloidosis
* Divided into macular and lichen amyloid
* Asian , Hispanic, and Middle Eastern
* Amyloid deposition contains keratin
* Histologic picture is similar for both
* Differ only in size of amyloid deposits
* Absence of amyloid deposits around blood vessels excludes systemic involvement
* Macular Amyloidosis: pruritic, brown macules with a rippled pattern

Lichen amyloidosis
* Pruritic, keratotic, hyperigmented plaques on the legs
* Tx = high potency corticosteroids, oral retinoids, cyclophosphamide, dermabrasion and occlusion
Extremities, trunk, genitals and face with localized nodules

* Lesions contain numerous plasma cells, amyloid is immunoglobulin-derived AL
* TX = physical removal or destruction

Secondary cutaneous amyloidosis
* Following PUVA therapy and in benign and malignant cutaneous neoplasms, deposits of amyloid may be found
* Most frequently associated neoplasms are NMSC and SKs
* In all cases, this is keratin-derived amyloid

Familial syndromes associated with amyloidosis (heredofamilial amyloidosis)
* Muckle-Wells syndrome
* MEN IIA
* Most present with neurologic disease and are now designated familial amyloidotic polyneuropathy
* Four types identified FAP I through IV
* AD inherited

PORPHYRIAS
* Porphyrinogens are the building blocks of hemoproteins
* Produced primarily in the liver, bone marrow and erythrocytes
* Each form is associated with a deficiency in the metabolic pathway of heme synthesis
* Absorption of UV radiation in the Soret band (400-410 nm) by the increased porphyrins leads to photosensitivity
* Activated porphyrins form reactive oxygen species that causes tissue damage

Current grouping of the porphyrias is based on the primary site of increased porphyrin production
* Erythropoietic forms
o Congenital erythropoietic porphyria (CEP)
o Erythropoietic protoporphyria (EPP)
o Erythropoietic coproporphyria ECP
* Hepatic forms
o Acute intermittent porphyria (AIP)
o ALA dehydrogenase deficiency
o Hereditary coproporphyria (HCP)
o Variegate porphyria (VP)
o Porphyria cutanea tarda

Porphyria cutanea tarda
* Most common porphyria
* Photosensitivity leads to bullae, which leads to ulcers, scarring, milia and dyspigmentation
* Hypertrichosis, fragility and skin thickening
* Alcoholism is common; Hep C in 94%
* Associated with DM, LE, HIV, and

estrogen therapy
* Multiple erosions with hemorrhagic crusts, as well as an intact blister on the lateral fourth finger

PCT in chronic renal failure
* Deficiency = uroporphyrinogen decarboxylase
* Most common = sporadic nonfamilial form, (80%), abnormal enzyme activity
* Presents in midlife
* Familial type = AD; deficiency in liver and RBCs
* Nonfamilial = acquired toxic; associated with exposure to hepatotoxins
* Diagnosis = suspected on clinical grounds
* Coral red fluorescence of urine
* 24 hour urine
* Uroporphyrins to coproporphyrins 3:1 to 5:1
* DIF shows IgG and C3 at the DEJ, and in the vessel walls in a linear pattern

Histologic features of PCT
* Subepidermal blister with minimal dermal inflammatory infiltrate. Festooning of dermal papillae.

treatment
* Remove environmental exposures
* Sunscreens
* Phlebotomy / uroporphyrinogen decarboxylase is inhibited by iron
o 500 ml at 2 week intervals, hemoglobin 10 g/dL
o Several months, 6-10 phlebotomies
* Antimalarials / full doses may produce severe hepatotoxic reaction
* Remission may last for years
* Iron chelation
* May respond to transplant in renal failure
* May improve with treatment if assoc. with Hep C

pseudoporphyria
* Skin and Histo similar to PCT
* Normal urine and serum porphyrins
* No hypertrichosis, dyspigmentation or cutaneous sclerosis
* Commonly caused by NSAIDs, naproxen, sunbed use, hemodialysis

treatment
* Sun protection
* Discontinue inciting medication
o May resolve over several months

Hepatoerythropoietic porphyria
* Very rare form / AR
* Deficiency of uroporphyrinogen decarboxylase, 10% of normal in both the liver and erythrocytes
* Dark urine at birth
* Vesicles, scarring, hypertrichosis, pigmentation, red fluorescence of teeth
* Abnormal urinary porphyrins as in PCT
* Elevated erythrocyte protoporphyrins
* Increased coproporphyrins

Hepatoerythropoietic porphyria
Acute intermittent porphyria
* Second most common form
* Characterized by periodic attacks of abdominal colic, gastrointestinal disturbances, paralyses, and psychiatric disorders
* No skin lesions are seen
* AD / deficiency in porphobilinogen deaminase
* Only 10 % develop disease, all are at risk for primary liver cancer
* Severe abdominal colic +/- NVDC
* Elevated urinary porphobilinogen
* Increased dALA in plasma and urine
* No specific treatment
* Avoid precipitating factors
* Glucose loading
* Hematin infusions
* Pain management
* Oral contraceptives may prevent attacks in women with premenstrual symptoms

Hereditary coproporphyria HCP
* Rare, AD
* Deficiency of coproporphyrinogen oxidase
* One third are photosensitive
* Prone to GI attacks
* Fecal coproporphyrin is always increased
* Urinary coproporphyrin, ALA, and PBG are only increased during attacks

Variegate porphyria VP
* AD
* Decreased activity of protoporphyrinogen oxidase
* Majority of relatives have silent VP
* Characterized by skin lesions of PCT and the GI and neurologic disease of AIP
* Suspect VP when finding indicate both PCT and AIP, esp. with history of South African ancestry
* Fecal coproporphyrins and protoporphyrins are always elevated
* During attacks, urine porphobilinogen and ALA are elevated
* Urinary coproporphyrins are increased over uroporphyrins
* A finding in the plasma of “X porphyrin,” fluorescence at 626 nm is characteristic and distinguishes this form from others
* Symptomatic treatment as for PCT and AIP

Erythropoietic protoporphyria EEP
* AD and AR forms
* Ferochelatase activity is 10 to 25% of normal in affected persons
* Typically presents in childhood, 2-5 years
* Burning of the skin upon sun exposure
* Elevated protoporphyrin IX absorbs both the Soret band and also at 500-600 nm
* Severe liver disease in 10%
* Excessive porphyrins are deposited in liver
* Diagnosis on clinical grounds
* Urine porphyrin levels are normal
* Erythrocyte protoporphyrin is elevated
* Erythrocyte, plasma, and fecal protoporphyrin can be assayed to confirm the diagnosis
* Skin biopsy confirms diagnosis
* Tx = sun protection
* Beta carotene, phototherapy, cysteine
* Transfusions for anemia

Erythropoietic protoporphyria
* Subtle scarring
Erythropoietic protoporphyria
* Erythema and hemorrhagic crusts
Congenital erythropoietic porphyria, CEP
* Gunther’s disease
* AR; defect of uroporphyrinogen III synthase
* Presents after birth with red urine
* Severe photosensitivity
* Blistering, scarring, ectropion and corneal damage
* Mutilating scars, hypertrichosis, profuse eyebrows, long eyelashes, “monkey face”
* Growth retardation, hemolytic anemia, thrombocytopenia, porphyrin gallstones, osteopenia
* Suspect in an infant with dark urine and photosensitivity

Congenital erythropoietic porphyria
* Erythrodontia
* Severe mutilation
* Fluorescence of circulating red blood cells, CEP with UVA
* Vs. transient fluorescence in EPP
* High amounts of uroporphyrin I and coproporphyrin I are found in the urine, stool and red cells
* Treatment – strict avoidance of sunlight and sometimes splenectomy for the hemolytic anemia
* Oral activated charcoal
* Repeated transfusions to maintain hematocrit level at 33% - turns off demand for heme
* Bone marrow transplantation
Transient erythroporphyria of infancy (purpuric phototherapy-induced eruption)

* Report of seven infants exposed to 380 to 700 nm blue lights, for the treatment of indirect hyperbilirubinemia, who developed marked purpura on the exposed skin
* All infants had received transfusions
* Elevated plasma coproporphyrins and protoporphyrins were found in 4
* Pathogenesis is unknown

Abnormalities In Dermal Connective Tissue.ppt

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Cardiac Assist Devices

Cardiac Assist Devices
By: Wayne E. Ellis, Ph.D., CRNA

Types
Pacemakers
AICDs
VADs

History
* First pacemaker implanted in 1958
* First ICD implanted in 1980
* Greater than 500,000 patients in the US population have pacemakers
* 115,000 implanted each year

Pacemakers Today
* Single or dual chamber
* Multiple programmable features
* Adaptive rate pacing
* Programmable lead configuration

Internal Cardiac Defibrillators (ICD)
* Transvenous leads
* Multiprogrammable
* Incorporate all capabilities of contemporary pacemakers
* Storage capacity

Temporary Pacing Indications
* Routes = Transvenous, transcutaneous, esophageal
* Unstable bradydysrhythmias
* Atrioventricular heart block
* Unstable tachydysrhythmias
* *Endpoint reached after resolution of the problem or permanent pacemaker implantation

Permanent Pacing Indications
* Chronic AVHB
* Chronic Bifascicular and Trifascicular Block
* AVHB after Acute MI
* Sinus Node Dysfunction
* Hypersensitive Carotid Sinus and Neurally Mediated Syndromes
* Miscellaneous Pacing Indications

Chronic AVHB
* Especially if symptomatic

Pacemaker most commonly indicated for:
* Type 2 2º
o Block occurs within or below the Bundle of His
* 3º Heart Block
o No communication between atria and ventricles

Chronic Bifascicular and Trifascicular Block
* Differentiation between uni, bi, and trifascicular block
* Syncope common in patients with bifascicular block
* Intermittent 3º heart block common

AVHB after Acute MI
* Incidence of high grade AVHB higher
* Indications for pacemaker related to intraventricular conduction defects rather than symptoms
* Prognosis related to extent of heart damage

Sinus Node Dysfunction
* Sinus bradycardia, sinus pause or arrest, or sinoatrial block, chronotropic incompetence
* Often associated with paroxysmal SVTs (bradycardia-tachycardia syndrome)
* May result from drug therapy
* Symptomatic?
* Often the primary indication for a pacemaker

Hypersensitive Carotid Sinus Syndrome
• Syncope or presyncope due to an exaggerated response to carotid sinus stimulation
• Defined as asystole greater than 3 sec due to sinus arrest or AVHB, an abrupt reduction of BP, or both

Neurally Mediated Syncope
* 10-40% of patients with syncope
* Triggering of a neural reflex
* Use of pacemakers is controversial since often bradycardia occurs after hypotension

Miscellaneous
* Hypertrophic Obstructive Cardiomyopathy
* Dilated cardiomyopathy
* Cardiac transplantation
* Termination and prevention of tachydysrhythmias
* Pacing in children and adolescents

Indications for ICDs
* Cardiac arrest due to VT/VF not due to a transient or reversible cause
* Spontaneous sustained VT
* Syncope with hemodynamically significant sustained VT or VF
* NSVT with CAD, previous MI, LV dysfunction and inducible VF or VT not suppressed by a class 1 antidysrhythmic

Device Selection
* Temporary pacing (invasive vs. noninvasive)
* Permanent pacemaker
* ICD

Pacemaker Characteristics
• Adaptive-rate pacemakers
•Single-pass lead Systems
• Programmable lead configuration
• Automatic Mode-Switching
• Unipolar vs. Bipolar electrode configuration

ICD selection
* Antibradycardia pacing
* Antitachycardia pacing
* Synchronized or nonsynchronized shocks for dysrhythmias
* Many of the other options incorporated into pacemakers

Approaches to Insertion
Mechanics
Unipolar Pacemaker
Bipolar Pacemaker
Indications
1. Sick sinus syndrome (Tachy-brady syndrome)
2. Symptomatic bradycardia
3. Atrial fibrillation
4. Hypersensitive carotid sinus syndrome
* Second-degree heart block/Mobitz II


Complete heart block
* Sinus arrest/block
* Tachyarrhythmias
Supraventricular, ventricular
To overdrive the arrhythmia
Atrial Fibrillation
1. Asynchronous/Fixed Rate
2. Synchronous/Demand
3. Single/Dual Chamber
4. Programmable/nonprogrammable
Synchronous/Demand
Examples of Demand Pacemakers
DDI
VVI/VVT
AAI/AAT
Disadvantage: Pacemaker may be fooled by interference and may not fire

Dual Chamber: A-V Sequential
Facilitates a normal sequence between atrial and ventricular contraction
Provides atrial kick + ventricular pacing
Atrial contraction assures more complete ventricular filling than the ventricular demand pacing unit
A-V Sequential
Disadvantage: More difficult to place
More expensive
Contraindication: Atrial fibrillation, SVT
Developed due to inadequacy of “pure atrial pacing”
Single Chamber
Atrial
Ventricular
“Pure Atrial Pacing”
Problems with Atrial Pacing
Electrode difficult to secure in atrium
Tends to float

Ventricular
Programmability
Table of Pacer Codes
Types of Pulse Generators
Examples
Other Information
Undersensing: Failure to sense ... much more in 105 slides

Cardiac Assist Devices.ppt

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