Chronic Blistering Dermatoses Part 2 and Nutritional Diseases Adam Wray, D.O. May 9, 2006

Chronic Blistering Chronic Blistering Dermatoses Part 2 Dermatoses Part 2

and Nutritional Diseasesand Nutritional Diseases

Adam Wray, D.O.Adam Wray, D.O.

May 9, 2006May 9, 2006

Pregnancy- Related Pregnancy- Related DermatosesDermatoses

Intrahepatic Cholestasis of PregnancyIntrahepatic Cholestasis of Pregnancy Polymorphic Eruption of PregnancyPolymorphic Eruption of Pregnancy Herpes (pemphigoid) gestationisHerpes (pemphigoid) gestationis Pruritic Urticarial Papules and Plaques Pruritic Urticarial Papules and Plaques

of Pregnancy (PUPPP)of Pregnancy (PUPPP) Papular Dermatitis of PregnancyPapular Dermatitis of Pregnancy Pruritic Folliculitis of PregnancyPruritic Folliculitis of Pregnancy

Intrahepatic Cholestasis of Intrahepatic Cholestasis of PregnancyPregnancy

Generalized pruritus and jaundiceGeneralized pruritus and jaundice No primary skin lesions, secondary No primary skin lesions, secondary

excoriationsexcoriations Caused by cholestasis, occurs late in Caused by cholestasis, occurs late in

pregnancy, resolves after deliverypregnancy, resolves after delivery Increased incidence of fetal comp.Increased incidence of fetal comp. 0.5% of pregnancies0.5% of pregnancies Tx: ursodeoxycholic acid more effective Tx: ursodeoxycholic acid more effective

than S-adenosyl-L-methioninethan S-adenosyl-L-methionine

Pruritic Urticarial Papules Pruritic Urticarial Papules and Plaques of Pregnancy and Plaques of Pregnancy

(PUPP)(PUPP) First reported in 1979First reported in 1979 Erythematous papules and plaques Erythematous papules and plaques

that begin as 1-2 mm lesions within that begin as 1-2 mm lesions within the abdominal striaethe abdominal striae

Spread over the course of a few days Spread over the course of a few days to involve the abdomen, buttocks, to involve the abdomen, buttocks, thighsthighs

Upper chest, face, and mucous Upper chest, face, and mucous membranes sparedmembranes spared

PUPPPPUPPP

Primigravidas 75% of the time, Primigravidas 75% of the time, usually does not recur with usually does not recur with subsequent pregnanciessubsequent pregnancies

Begins late in third trimester and Begins late in third trimester and resolves with deliveryresolves with delivery

May be associated with increase May be associated with increase weight gain weight gain More common in those carrying More common in those carrying

twins/tripletstwins/triplets

PUPPPPUPPP

Histology: Histology: perivascular perivascular infiltrate in upper infiltrate in upper and mid dermis, and mid dermis, epidermis normalepidermis normal

DIF negativeDIF negative Tx: topical or oral Tx: topical or oral

steroidssteroids

Papular Dermatitis of Papular Dermatitis of PregnancyPregnancy

Controversial entityControversial entity Pruritic generalized eruption of 3-5 mm Pruritic generalized eruption of 3-5 mm

erythematous papules surmounted by a erythematous papules surmounted by a small, firm, central crust small, firm, central crust

May erupt at any time during pregnancy May erupt at any time during pregnancy and resolve with deliveryand resolve with delivery

Marked elevation of 24 hr urine HCGMarked elevation of 24 hr urine HCG Tx: oral steroids, may recur in subsequent Tx: oral steroids, may recur in subsequent

pregnanciespregnancies

Prurigo Gestationis Prurigo Gestationis (Besnier)(Besnier)

Pruritic, excoriated Pruritic, excoriated papules of the papules of the proximal limbs and proximal limbs and upper trunkupper trunk

Onset is 20-34 weeks Onset is 20-34 weeks gestationgestation

Clears in postpartum Clears in postpartum period and does not period and does not recurrecur

Tx: topical steroids Tx: topical steroids

Pruritic Folliculitis of Pruritic Folliculitis of PregnancyPregnancy

22ndnd or 3 or 3rdrd trimester trimester Small follicular pustules scattered Small follicular pustules scattered

widely over the trunkwidely over the trunk May be a type of hormonally induced May be a type of hormonally induced

acneacne

Impetigo HerpetiformisImpetigo Herpetiformis

Form of severe pustular psoriasis Form of severe pustular psoriasis occurring in pregnancyoccurring in pregnancy

Acute, usually febrile onset of grouped Acute, usually febrile onset of grouped pustules on an erythematous base pustules on an erythematous base

Begins in the groin, axillae, and neckBegins in the groin, axillae, and neck Increased WBC, hypocalcemia Increased WBC, hypocalcemia Recurs with pregnancy, fetal death due to Recurs with pregnancy, fetal death due to

placental insufficiencyplacental insufficiency Tx: prednisone 1mg/kgTx: prednisone 1mg/kg

Cicatricial Pemphigoid Cicatricial Pemphigoid (Benign Mucosal (Benign Mucosal

Pemphigoid)Pemphigoid) Vesicles which quickly rupture, leaving Vesicles which quickly rupture, leaving

erosions and ulcers with scarringerosions and ulcers with scarring Primarily occur on mucous membranes, Primarily occur on mucous membranes,

conjunctiva (66%) and oral mucosa (90%)conjunctiva (66%) and oral mucosa (90%) Oral mucosa may be the only affected site Oral mucosa may be the only affected site

for years; desquamative gingivitis of for years; desquamative gingivitis of buccal mucosa buccal mucosa

Ocular complications: bilateral, flaccid Ocular complications: bilateral, flaccid vesicles on conjuntivia, xerosis, vesicles on conjuntivia, xerosis, symblepharon, and blindness may result.symblepharon, and blindness may result.

Generally confined to head and neckGenerally confined to head and neck

Cicatricial PemphigoidCicatricial Pemphigoid

Tends to affect middle-aged to elderly Tends to affect middle-aged to elderly women 2:1 female/malewomen 2:1 female/male

Ddx; oral lichen planus (biopsy and IF)Ddx; oral lichen planus (biopsy and IF) Chronic disease that may lead to slowly Chronic disease that may lead to slowly

progressive shrinkage of the ocular progressive shrinkage of the ocular mucous membranes and blindnessmucous membranes and blindness

Also occurs in pharynx, esophagus, larynx, Also occurs in pharynx, esophagus, larynx, nose, penis, vagina, anal mucosa, nose, penis, vagina, anal mucosa, deafnessdeafness


Cutaneous lesions in 25%; tense bullaeCutaneous lesions in 25%; tense bullae Bullae heal with or without scarring, occur on the Bullae heal with or without scarring, occur on the

face, scalp, neck, and inguinal region and face, scalp, neck, and inguinal region and extremitiesextremities

Some pts may have antibodies targeted against Some pts may have antibodies targeted against classic bullous pemphigoid antigens and should classic bullous pemphigoid antigens and should be classified as “mucosal predominate bullous be classified as “mucosal predominate bullous pemphigoid”pemphigoid”

Chronic course, pts health not usually affectedChronic course, pts health not usually affected IgA antibodies may explain mucosal scarring IgA antibodies may explain mucosal scarring

tendencytendency


Little tendency to remission (unlike Little tendency to remission (unlike bullous pemphigoid)bullous pemphigoid)

Subtypes include types that target Subtypes include types that target basement membrane zone antigens basement membrane zone antigens (laminin, glycoproteins,)(laminin, glycoproteins,) Intracellular C-terminal domain of BP-180Intracellular C-terminal domain of BP-180 Laminin 5 (antiepiligrin cicatricial Laminin 5 (antiepiligrin cicatricial

pemphigoid)pemphigoid) Beta4 subunit of alpha6beta4 integrinBeta4 subunit of alpha6beta4 integrin


Direct IF testing C3 and IgG at the Direct IF testing C3 and IgG at the lamina lucida in 80-95%lamina lucida in 80-95%

Tx: mild cases topical steroids Tx: mild cases topical steroids (Temovate/Orabase), intralesional (Temovate/Orabase), intralesional triamcinolone every 2-4 weekstriamcinolone every 2-4 weeks

Tx: Dapsone, prednisone, Tx: Dapsone, prednisone, Azathioprine or cyclophosphamide, Azathioprine or cyclophosphamide, cyclosporine, TCNcyclosporine, TCN

Epidermolysis Bullosa Epidermolysis Bullosa AcquisitaAcquisita

Antibodies to Type VII collagenAntibodies to Type VII collagen Skin fragility, healing with scarsSkin fragility, healing with scars Bullous eruption, scaring, miliaBullous eruption, scaring, milia Histo: epidermal necrosis, subepidermal Histo: epidermal necrosis, subepidermal

blister, dermal necrosis, lack of blister, dermal necrosis, lack of inflammation until lesions become older.inflammation until lesions become older.

IgG deposition on dermal side of salt-splitIgG deposition on dermal side of salt-split Associations: myeloma, granulomatous Associations: myeloma, granulomatous

colitis, diabetes, lymphoma, leukemia, colitis, diabetes, lymphoma, leukemia, amyloidosis, and carcinomaamyloidosis, and carcinoma

EBAEBA

IgG on floor of blister, in contrast to pemphigoid.

EBA criteria proposed in 1971 EBA criteria proposed in 1971 by Roenigkby Roenigk

1) clinical lesions of EBA1) clinical lesions of EBA 2) adult onset2) adult onset 3) lack of a family hx of EB3) lack of a family hx of EB 4) exclusion of all other bullous dz4) exclusion of all other bullous dz 5) IgG at BMZ by DIF5) IgG at BMZ by DIF 6) blister beneath basal lamina6) blister beneath basal lamina 7) deposition of IgG beneath basal 7) deposition of IgG beneath basal

laminalamina

Epidermolysis Bullosa Epidermolysis Bullosa AcquisitaAcquisita

Tx; unsatisfactory, steroids, Tx; unsatisfactory, steroids, dapsone, colchicine, IV dapsone, colchicine, IV Immunoglobulin, CyclosporinImmunoglobulin, Cyclosporin

Dermatitis HerpetiformisDermatitis Herpetiformis

Chronic, relapsing, severely pruritic dzChronic, relapsing, severely pruritic dz Grouped symmetrical, polymorphous, Grouped symmetrical, polymorphous,

erythematous-based lesionserythematous-based lesions May be papular, papulovesicular, May be papular, papulovesicular,

vesiculobullous, bullous, or urticarialvesiculobullous, bullous, or urticarial Linear petechial lesions on palms, fingersLinear petechial lesions on palms, fingers Pigmented spots over lumbosacral regionPigmented spots over lumbosacral region

Itching and burning are intenseItching and burning are intense Spontaneous remissions lasting a weekSpontaneous remissions lasting a week


Laryngeal lesions Laryngeal lesions hoarseness hoarseness

Premenstrual flares Premenstrual flares may occurmay occur

Oral iodides may Oral iodides may flare dzflare dz


Very few patients with DH ever have Very few patients with DH ever have diarrhea although DH is associated with diarrhea although DH is associated with Gluten-sensitive-enteropathy (GSE)Gluten-sensitive-enteropathy (GSE)

87% of pts with DH and IgA deposits in the 87% of pts with DH and IgA deposits in the skin are HLA-B8 positive (like GSE)skin are HLA-B8 positive (like GSE)

Gluten is a protein found in cereals except Gluten is a protein found in cereals except for rice, oats, and cornfor rice, oats, and corn

IgA antibodies are formed in the jejunum, IgA antibodies are formed in the jejunum, may deposit in the skin may deposit in the skin


Associated with; Thyroid disorders, Associated with; Thyroid disorders, small bowel lymphoma, non-small bowel lymphoma, non-Hodgkins lymphomaHodgkins lymphoma

70-100% of pts have abnormalities of 70-100% of pts have abnormalities of the jejunal mucosathe jejunal mucosa

Gluten-free diet decreases Dapsone Gluten-free diet decreases Dapsone dose requirements after 3-4 monthsdose requirements after 3-4 months


Ddx: pemphigoid, EM, scabies, Ddx: pemphigoid, EM, scabies, contact dermatitis, atopic dermatitis, contact dermatitis, atopic dermatitis, eczema, insect bites, pruigo eczema, insect bites, pruigo nodularisnodularis

IgA in a granular pattern in the IgA in a granular pattern in the dermal papillae in normal skin is dermal papillae in normal skin is specific and pathognomonic for specific and pathognomonic for DHDH


IgA deposits may be focal, so IgA deposits may be focal, so multiple biopsies may be needed.multiple biopsies may be needed.

Deposits of the antibody are more Deposits of the antibody are more often seen in previously involved skin often seen in previously involved skin or normal appearing skin adjacent to or normal appearing skin adjacent to involved skin involved skin


Equal male:femaleEqual male:female Onset between 20 to 40 yearsOnset between 20 to 40 years Tx: Dapsone 50-300mg daily (hemolytic Tx: Dapsone 50-300mg daily (hemolytic

anemia, methemoglobinemia, check anemia, methemoglobinemia, check G6PD prior to tx) monitor Hct,WBCs, G6PD prior to tx) monitor Hct,WBCs, LFTsLFTs

Tx: Sulfapyridine 0.5g QID to 2-4g/dayTx: Sulfapyridine 0.5g QID to 2-4g/day Gluten-free diet will decrease need for Gluten-free diet will decrease need for

meds or allow pt to go off themmeds or allow pt to go off them

Linear IgA Bullous Linear IgA Bullous DermatosisDermatosis

Subepidermal blisters, a neutrophillic Subepidermal blisters, a neutrophillic infiltrate, circulating IGA infiltrate, circulating IGA antibasement membrane zone antibasement membrane zone antibodyantibody

Deposition of IgA antibody at the Deposition of IgA antibody at the dermoepidermal junction by direct IFdermoepidermal junction by direct IF

Linear IgA Bullous Linear IgA Bullous Dermatosis Adult FormDermatosis Adult Form

Acquired autoimmune blistering diseaseAcquired autoimmune blistering disease Clinical pattern similar to dermatitis Clinical pattern similar to dermatitis

herpetiformis, or with vesicles and bullae in herpetiformis, or with vesicles and bullae in a bullous pemphigoid-like appearancea bullous pemphigoid-like appearance

50% mucous membrane involvement50% mucous membrane involvement Oral and conjunctival lesions may be Oral and conjunctival lesions may be

scarringscarring No association with enteropathy or with No association with enteropathy or with

HLA-B8HLA-B8 Tends to remit over several yearsTends to remit over several years

Linear IgA Bullous Linear IgA Bullous Dermatosis Dermatosis Adult FormAdult Form

Linear IgA dermatosis can occur as a drug-Linear IgA dermatosis can occur as a drug-induced disease:induced disease:

Self-limited, less mucosal involvement, Self-limited, less mucosal involvement, usually does not have circulating usually does not have circulating autoantibodyautoantibody

IgA is usually deposited in the subbasal IgA is usually deposited in the subbasal lamina arealamina area

Vanco, Lithium, amiodarone, carbamazapine, Vanco, Lithium, amiodarone, carbamazapine, captopril, PCN, PUVA, lasix, dilantin, captopril, PCN, PUVA, lasix, dilantin, oxaprozin, statins, tea tree oil, and others oxaprozin, statins, tea tree oil, and others

Linear IgA Bullous Linear IgA Bullous Dermatosis Adult FormDermatosis Adult Form

Histo: papillary dermal microabscess with Histo: papillary dermal microabscess with neutrophils, subepidermal bullae may be seen neutrophils, subepidermal bullae may be seen with neutrophils and eosinophilswith neutrophils and eosinophils

Direct IF: homogeneous linear deposition of IgA Direct IF: homogeneous linear deposition of IgA is present at the BMZis present at the BMZ

Indirect IF: few will have circulating IgA Indirect IF: few will have circulating IgA autoantibody with anti-BMZ specificityautoantibody with anti-BMZ specificity

On salt-split, deposition of IgA may be on the On salt-split, deposition of IgA may be on the roof, base, or a combination of both.roof, base, or a combination of both.

Tx: Dapsone, topical steroidsTx: Dapsone, topical steroids

Linear IgA Bullous Linear IgA Bullous Dermatosis Childhood FormDermatosis Childhood Form Chronic Bullous Disease of Childhood: Chronic Bullous Disease of Childhood:

acquired, self-limited bullous disease acquired, self-limited bullous disease Onset by 2 or 3, remits by age 13Onset by 2 or 3, remits by age 13 Bullae develop on erythematous or normal Bullae develop on erythematous or normal

appearing skinappearing skin Trunk, buttocks, genitalia, and thighsTrunk, buttocks, genitalia, and thighs Perioral and scalp lesions are common, oral Perioral and scalp lesions are common, oral

lesions not uncommonlesions not uncommon Bullae arranged in a rosette or annular Bullae arranged in a rosette or annular

array “cluster of jewels”array “cluster of jewels”

Linear IgA Bullous Linear IgA Bullous Dermatosis Childhood FormDermatosis Childhood Form Histo: subepidermal bullae filled with Histo: subepidermal bullae filled with

neutrophils, eosinophils may predominateneutrophils, eosinophils may predominate Direct IF: linear deposition of IgA at the BMZDirect IF: linear deposition of IgA at the BMZ Indirect IF: positive for circulating IgA antibodies Indirect IF: positive for circulating IgA antibodies

in 50%in 50% Tx: Sulfapyridine or dapsone, topical steroids Tx: Sulfapyridine or dapsone, topical steroids In contrast to adults, children show increased In contrast to adults, children show increased

frequency of B8, DR3, and DQ2 HLA antigens.frequency of B8, DR3, and DQ2 HLA antigens.

Transient Acantholytic Transient Acantholytic DermatosisDermatosis

Over age 50, strong male Over age 50, strong male predominacepredominace

Fragile vesicles, limited Fragile vesicles, limited extent, sparse, limited extent, sparse, limited durationduration

Rapid crusting, keratotic Rapid crusting, keratotic erosion <1cmerosion <1cm

Usually chest, shoulder girdle, Usually chest, shoulder girdle, and/or upper abdomenand/or upper abdomen

Patients at strict bedrest Patients at strict bedrest higher incidence.higher incidence.

Direct IF is negativeDirect IF is negative Tx: topical steroids, Tx: topical steroids,

isotretinoin, dapsone, PUVAisotretinoin, dapsone, PUVA

Nutritional Diseases Nutritional Diseases Andrews Chapter 22Andrews Chapter 22

Nutritional DiseasesNutritional Diseases

Caused by insufficiency or excess of Caused by insufficiency or excess of dietary essentialsdietary essentials

Common in underdeveloped countries, Common in underdeveloped countries, infants and childreninfants and children

Often pts have features of several Often pts have features of several disorders if diet is generally restricteddisorders if diet is generally restricted

Alcoholism is the main cause in developed Alcoholism is the main cause in developed countriescountries Postoperative pts, psychiatric pts (anorexia Postoperative pts, psychiatric pts (anorexia

nervosa, bulimia), surgical or inflammatory nervosa, bulimia), surgical or inflammatory bowel dysfunction, Crohn’s bowel dysfunction, Crohn’s

Hypovitaminosis A Hypovitaminosis A (Phrynoderma) (Phrynoderma)

Vitamin A: fat soluble found in milk, fish Vitamin A: fat soluble found in milk, fish oil, liver, eggs, and as carotenoids in oil, liver, eggs, and as carotenoids in plantsplants

Common in children in developing worldCommon in children in developing world Developed countries found in diseases of Developed countries found in diseases of

fat malabsorption; Crohn’s, celiac, cystic fat malabsorption; Crohn’s, celiac, cystic fibrosis, cholestatic liver disease, bowel fibrosis, cholestatic liver disease, bowel bypass surgery for obesity.bypass surgery for obesity.

Vitamin A required for keratinization of Vitamin A required for keratinization of mucosal surfacesmucosal surfaces

Hypovitaminosis AHypovitaminosis A

Abnormal keratinization leads to increased Abnormal keratinization leads to increased mortality from inflammatory disease of the mortality from inflammatory disease of the gut and lung ie; diarrhea and pneumoniagut and lung ie; diarrhea and pneumonia

PhrynodermaPhrynoderma or “toadskin” resembles or “toadskin” resembles keratosis pilaris. keratosis pilaris.

Keratotic papules over extremities and Keratotic papules over extremities and shoulders arising from pilosebaceous shoulders arising from pilosebaceous folliclesfollicles

Hypovitaminosis A Hypovitaminosis A Ocular Findings Ocular Findings

Major cause of blindness in children in the Major cause of blindness in children in the

developing world!developing world! Earliest finding is delayed adaptation to Earliest finding is delayed adaptation to

the dark (nyctalopia)the dark (nyctalopia) Night blindness, xeropthalmia, xerosis Night blindness, xeropthalmia, xerosis

corneae, keratomalaciacorneae, keratomalacia Bitot’s Spots;Bitot’s Spots; circumscribed areas of circumscribed areas of

xerosis of the conjuctiva lateral to the xerosis of the conjuctiva lateral to the corneacornea

Hypovitaminosis AHypovitaminosis A

Diagnosis: based on eye findings, Diagnosis: based on eye findings, serum Vitamin A level.serum Vitamin A level.

Tx: 300,000 IU Vitamin A followed by Tx: 300,000 IU Vitamin A followed by the recommended dietary the recommended dietary requirementrequirement

Hypervitaminosis AHypervitaminosis A

Skin findings similar to side effects of Skin findings similar to side effects of Retinoid therapy. Children are at greater Retinoid therapy. Children are at greater risk as well as dialysis patients. risk as well as dialysis patients.

Loss of hair and coarseness, loss of Loss of hair and coarseness, loss of eyebrows, exfoliation and pigmentation of eyebrows, exfoliation and pigmentation of skin, clubbing, hepatosplenomegaly, skin, clubbing, hepatosplenomegaly, anemia, increased LFTs, pseudotumor anemia, increased LFTs, pseudotumor cerebri with papilledema, premature cerebri with papilledema, premature closure of epiphyses closure of epiphyses

Hypervitaminosis A Hypervitaminosis A AdultsAdults

Early signs are dryness of the lips and Early signs are dryness of the lips and anorexia. Followed by bone and joint anorexia. Followed by bone and joint pains, follicular hyperkeratosis, brawny pains, follicular hyperkeratosis, brawny desquamation of the skin, loss of scalp desquamation of the skin, loss of scalp hair and eyebrows, dystrophy of the nails.hair and eyebrows, dystrophy of the nails.

Fatigue, myalgia, depression, anorexia, Fatigue, myalgia, depression, anorexia, liver diseaseliver disease

Birth defects with excess Vit A in Birth defects with excess Vit A in pregnancy pregnancy

Vitamin DVitamin D

Deficiency of Vitamin D causes Deficiency of Vitamin D causes alopecia, osteomalaciaalopecia, osteomalacia

Vitamin D overdose can cause Vitamin D overdose can cause hypercalcemia and calcinosis.hypercalcemia and calcinosis.

Vitamin E DeficiencyVitamin E Deficiency

Most common in infants of low birth Most common in infants of low birth weightweight

Peripheral edema, progressive Peripheral edema, progressive neuromyopathy, and neuromyopathy, and ophthalmoplegiaophthalmoplegia

Vitamin K DeficiencyVitamin K Deficiency

Dietary deficiency of vitamin K, a fat Dietary deficiency of vitamin K, a fat soluble vitamin, does not occur in adults soluble vitamin, does not occur in adults because it is synthesized by bacteria in because it is synthesized by bacteria in the large intestinethe large intestine

Liver and biliary disease, cystic fibrosis, Liver and biliary disease, cystic fibrosis, and anorexia nervosa causes deficiencyand anorexia nervosa causes deficiency

Drugs: coumadin, salicylates, Drugs: coumadin, salicylates, cholestyramine, and possibly cholestyramine, and possibly cephalosporinscephalosporins

Vitamin K DeficiencyVitamin K Deficiency

Decrease in the vitamin K-dependent Decrease in the vitamin K-dependent clotting factor II, VII, IX, and X.clotting factor II, VII, IX, and X.

Purpura, hemorrhage, and Purpura, hemorrhage, and ecchymosis.ecchymosis.

Tx: 5 to 10 mg/day IM Vit K for 2-3 Tx: 5 to 10 mg/day IM Vit K for 2-3 daysdays

Vitamin B1 DeficiencyVitamin B1 Deficiency

Thiamine deficiency results in Thiamine deficiency results in Beriberi Beriberi

Edema, and peripheral neuropathyEdema, and peripheral neuropathy


Riboflavin deficiency is Riboflavin deficiency is seen most often in seen most often in alcoholics.alcoholics.

Phototherapy for neonatal Phototherapy for neonatal icterus, boric acid icterus, boric acid ingestion, hypothyroidism, ingestion, hypothyroidism, chlorpromazinechlorpromazine

Oral-ocular-genital Oral-ocular-genital Syndrome: Syndrome: angular angular chelitis, atrophic tongue, chelitis, atrophic tongue, photophobia, blepharitis, photophobia, blepharitis, confluent dermatitis of confluent dermatitis of scrotumscrotum

Tx: 5mg Riboflavin qdTx: 5mg Riboflavin qd

Vitamin B6- Pyridoxine Vitamin B6- Pyridoxine

Deficiency: occurs in uremia and cirrhosisDeficiency: occurs in uremia and cirrhosis Seborrheic dermatitis, glossitis, chelitis, Seborrheic dermatitis, glossitis, chelitis,

conjunctivitis, confusion, neuropathyconjunctivitis, confusion, neuropathy Somnolence, confusion, and neuropathySomnolence, confusion, and neuropathy Excess: subepidermal vesicular Excess: subepidermal vesicular

dermatosis, peripheral sensory dermatosis, peripheral sensory neuropathyneuropathy

Vitamin B12 Deficiency Vitamin B12 Deficiency CyanocobalaminCyanocobalamin

Absorbed through the distal ileum after Absorbed through the distal ileum after binding to gastric intrinsic factor in an acid binding to gastric intrinsic factor in an acid ph.ph.

Deficiency caused by: decreased intrinsic Deficiency caused by: decreased intrinsic factor, achlorhydria, malabsorption factor, achlorhydria, malabsorption syndromes (pancreatic, sprue)syndromes (pancreatic, sprue)

Because of large body stores in adults, Because of large body stores in adults, deficiency occurs 3 to 6 years after onset deficiency occurs 3 to 6 years after onset of GI disease! of GI disease!


Glossitis, hyperpigmentation Glossitis, hyperpigmentation accentuated in exposed areas accentuated in exposed areas resembling Addison’s diseaseresembling Addison’s disease

Megaloblastic anemia, weakness, Megaloblastic anemia, weakness, paresthesias, ataxiaparesthesias, ataxia

Tx: IM B12, neuro defects may not Tx: IM B12, neuro defects may not improveimprove

Folic Acid DeficiencyFolic Acid Deficiency

Diffuse hyperpigmentation, glossitis, Diffuse hyperpigmentation, glossitis, chelitis, and megaloblastic anemiachelitis, and megaloblastic anemia

Scurvy Scurvy Vitamin C DeficiencyVitamin C Deficiency

Most common vitamin deficiency dxd Most common vitamin deficiency dxd by dermalologistsby dermalologists

Elderly alcoholics and psychiatric ptsElderly alcoholics and psychiatric pts

Scurvy Scurvy “ “The Four H’s”The Four H’s”

Hemorrhagic signsHemorrhagic signs Hyperkeratosis of the hair folliclesHyperkeratosis of the hair follicles HypochondriasisHypochondriasis Hematologic abnormalitiesHematologic abnormalities

ScurvyScurvy

Perifollicular petechiae and ecchymoses, Perifollicular petechiae and ecchymoses, subungual, subconjunctival, intramuscular, subungual, subconjunctival, intramuscular, and intraarticular hemorrhageand intraarticular hemorrhage

““Corkscrew hairs”; hairshafts are curled in Corkscrew hairs”; hairshafts are curled in follicles capped by keratotic plugsfollicles capped by keratotic plugs

Hemorrhagic gingivitis; bleeding gums, Hemorrhagic gingivitis; bleeding gums, epistaxis, anemiaepistaxis, anemia

ScurvyScurvy

Dx: serum ascorbic acid levelDx: serum ascorbic acid level Tx: ascorbic acid 1000mg qd x 1 Tx: ascorbic acid 1000mg qd x 1

week; maintenance of 100 mg/dayweek; maintenance of 100 mg/day

Niacin Deficiency Niacin Deficiency PellagraPellagra

Nicotinic acid, vitamin Nicotinic acid, vitamin B3, niacin or its B3, niacin or its precursor tryptophan is precursor tryptophan is associated with a diet associated with a diet entirely composed of entirely composed of corn, millet or sorghumcorn, millet or sorghum

Other vitamin Other vitamin deficiencies or deficiencies or malnutrition coexistmalnutrition coexist

Most cases are alcoholics Most cases are alcoholics in developed countriesin developed countries

Pellagra Pellagra CausesCauses

Carcinoid tumors, which divert tryptophan to Carcinoid tumors, which divert tryptophan to serotoninserotonin

Hartnup dz (impaired absorption of tryptophan)Hartnup dz (impaired absorption of tryptophan) Intestinal parasites esp; hookwormIntestinal parasites esp; hookworm GI diseases ie Crohn’s and GI surgeryGI diseases ie Crohn’s and GI surgery IV alimentationIV alimentation Anorexia nervosaAnorexia nervosa Meds; Isoniazid, azathioprine, 5-FU, HydantoinsMeds; Isoniazid, azathioprine, 5-FU, Hydantoins

PellagraPellagra

Chronic disease affecting Chronic disease affecting GI tract, CNS, skinGI tract, CNS, skin

““3 D’s”; diarrhea, 3 D’s”; diarrhea, dementia, dermatitisdementia, dermatitis

Dermatitis: Dermatitis: photosensative eruption, photosensative eruption, perineal lesions, perineal lesions, thickening and thickening and pigmentation over boney pigmentation over boney prominences, seborrheic prominences, seborrheic dermatitis-like eruption dermatitis-like eruption on faceon face

PellagraPellagra

Photosensitive eruption Photosensitive eruption on face, neck, cheston face, neck, chest

(Casal’s necklace), (Casal’s necklace), eruption may be eruption may be vesicular or bullous vesicular or bullous (wet pellagra)(wet pellagra)

After several After several phototoxic events the phototoxic events the skin shows skin shows hyperpigmentation, hyperpigmentation, scaling, a copper huescaling, a copper hue

Scrotal and perineal Scrotal and perineal erosions, fissures, erosions, fissures, angular cheilitis angular cheilitis

PellagraPellagra

CNS and GI symptoms CNS and GI symptoms may occur without may occur without skin changes; apathy, skin changes; apathy, muscle weakness, muscle weakness, paresthesias, paresthesias, dizziness, psychosisdizziness, psychosis

Disease is Disease is progressive, majority progressive, majority of pts die in 4-5 years of pts die in 4-5 years if untreated if untreated

Pellagra Pellagra Diagnosis and TreatmentDiagnosis and Treatment

Diet: Animal proteins, eggs, milk, Diet: Animal proteins, eggs, milk, vegetablesvegetables

100mg nicotinamide qid100mg nicotinamide qid Skin lesions begin to resolve within Skin lesions begin to resolve within

24 hours of tx24 hours of tx Alcoholism should be addressed and Alcoholism should be addressed and

treatedtreated

Biotin DeficiencyBiotin Deficiency

Biotin is universally available and is Biotin is universally available and is produced by intestinal bacteriaproduced by intestinal bacteria

Deficiency is rare, can occur in short gut, Deficiency is rare, can occur in short gut, malabsorption, long term antibx, ingestion malabsorption, long term antibx, ingestion of avidin (found in raw egg white), and of avidin (found in raw egg white), and valproic acid treatment in childrenvalproic acid treatment in children

Dermatitis is perioral; patchy, red, eroded Dermatitis is perioral; patchy, red, eroded lesions on the face and groin. May lesions on the face and groin. May resemble Zn deficiency.resemble Zn deficiency.

Candida overgrowth of lesions occursCandida overgrowth of lesions occurs

BiotinBiotin

Alopecia including loss of eyebrows and Alopecia including loss of eyebrows and eyelasheseyelashes

Neuro: depression, lethargy, paresthesiasNeuro: depression, lethargy, paresthesias Infants: hypotonia, lethargy seizures, Infants: hypotonia, lethargy seizures,

developmental delaysdevelopmental delays Inherited form: detecting organic Inherited form: detecting organic

aminoaciduria with 3-hydroxyisovaleric acidaminoaciduria with 3-hydroxyisovaleric acid Tx: 10mg Biotin qd Skin lesions resolve Tx: 10mg Biotin qd Skin lesions resolve

rapidly, but neuro damage may be rapidly, but neuro damage may be permanent permanent

Zinc DeficiencyZinc Deficiency

Inherited or AquiredInherited or Aquired Inherited: Acrodermatitis Inherited: Acrodermatitis

enteropathicaenteropathica Premies at risk due to inadequate body Premies at risk due to inadequate body

zinc storeszinc stores Weaning from breast milk precipitates Weaning from breast milk precipitates

clinical zinc deficiencyclinical zinc deficiency Parental nutrition without adequate Parental nutrition without adequate

zinc content may contributezinc content may contribute

ZincZinc

Acquired: alcoholics, bowel disease, Acquired: alcoholics, bowel disease, anorexia, AIDSanorexia, AIDS

Zinc requirements increase with Zinc requirements increase with metabolic stressmetabolic stress

Diets containing mainly cereal grains Diets containing mainly cereal grains are high in phytate, which binds zinc, are high in phytate, which binds zinc, Middle East, North AfricaMiddle East, North Africa

ZincZincDermatitisDermatitis

Pustular and bullous, acral and perioralPustular and bullous, acral and perioral Patchy, red, dry, scaling with Patchy, red, dry, scaling with

exudation and crusts. Angular cheilitis exudation and crusts. Angular cheilitis and stomatitisand stomatitis

Nail dystrophy, alopeciaNail dystrophy, alopecia Diarrhea, growth retardation, CNSDiarrhea, growth retardation, CNS Histo: vacuolation of the keratinocytes Histo: vacuolation of the keratinocytes

of the upper stratum malpighii of the upper stratum malpighii

Zinc Deficiency Zinc Deficiency Diagnosis and TreatmentDiagnosis and Treatment

Characteristic skin findings, acral or perioral Characteristic skin findings, acral or perioral dermatitis dermatitis

Chronic diaper rash with diarrhea in an infant Chronic diaper rash with diarrhea in an infant should lead to evaluation for zinc deficiency should lead to evaluation for zinc deficiency

Diagnosis: low serum zinc, alkaline Diagnosis: low serum zinc, alkaline phosphatase phosphatase

Tx: zinc sulfate 1-2 mg/kg/dayTx: zinc sulfate 1-2 mg/kg/day Tx: acrodermatitis enteropathica is lifelong Tx: acrodermatitis enteropathica is lifelong

and recommend 3mg/kg of Zn. Caution: may and recommend 3mg/kg of Zn. Caution: may lead to low serum copper levelslead to low serum copper levels

Essential Fatty Acid Essential Fatty Acid DeficiencyDeficiency

Lbw infants, bowel disease, alimentation, Lbw infants, bowel disease, alimentation, cystic fibrosiscystic fibrosis

Dermatitis similar to zinc def : xerosis, Dermatitis similar to zinc def : xerosis, EFA’s constitute 25% of the fatty acids of EFA’s constitute 25% of the fatty acids of the stratum corneumthe stratum corneum

Widespread erythema, intertriginous Widespread erythema, intertriginous weeping eruption, infection, alopeciaweeping eruption, infection, alopecia

Decrease in linoleic acid and an increase Decrease in linoleic acid and an increase in palmitoleic and oleic acidsin palmitoleic and oleic acids

EFA DeficiencyEFA Deficiency

Ratio of eicosatrienoic acid to Ratio of eicosatrienoic acid to arachidonic acid of >0.4 is diagnosticarachidonic acid of >0.4 is diagnostic

Tx: Intralipid 10% IVTx: Intralipid 10% IV

Iron DeficiencyIron Deficiency

Common in menstruationCommon in menstruation Mucocutaneous; glossitis, angular Mucocutaneous; glossitis, angular

chelitis, pruritus, telogen effluviumchelitis, pruritus, telogen effluvium Plummer-Vinson syndrome:Plummer-Vinson syndrome:

microcytic anemia, dysphagia, microcytic anemia, dysphagia, glossitis (middle aged women) thin glossitis (middle aged women) thin lips, narrow mouth, koilonychia in 50%lips, narrow mouth, koilonychia in 50%

Post-cricoid esophageal webPost-cricoid esophageal web

Iron DeficiencyIron Deficiency

Diagnosis: serum iron (Fe+)Diagnosis: serum iron (Fe+) Tx: iron sulfate 325 mg tidTx: iron sulfate 325 mg tid

Selenium DeficiencySelenium Deficiency

IV alimentation, poor soil selenium IV alimentation, poor soil selenium content, lbw infantscontent, lbw infants

Children: hypopigmentation of skin Children: hypopigmentation of skin and hair (psuedoalbinism), and hair (psuedoalbinism), leukonychialeukonychia

Cardiomyopathy, muscle pain, Cardiomyopathy, muscle pain, elevated muscle enzymes (cpk)elevated muscle enzymes (cpk)

Tx: 3 ug/kg/day selenium Tx: 3 ug/kg/day selenium

Protein-energy MalnutritionProtein-energy Malnutrition

Spectrum of diseases: marasmus, Spectrum of diseases: marasmus, kwashiorkor, and marasmic kwashiorkorkwashiorkor, and marasmic kwashiorkor

Endemic in developing worldEndemic in developing world Marasmus; def of protein and calories, Marasmus; def of protein and calories,

children < 60% of IBW without edemachildren < 60% of IBW without edema Kwashiorkor; protein def, 60-80% of Kwashiorkor; protein def, 60-80% of

IBW with edema or hypoproteinemia IBW with edema or hypoproteinemia

Marasmus/ KwashiorkorMarasmus/ Kwashiorkor

Cystic fibrosis, dietary restrictionsCystic fibrosis, dietary restrictions Marasmus: skin is dry, wrinkled, looseMarasmus: skin is dry, wrinkled, loose ““Monkey facies”;Monkey facies”; due to lose of buccal due to lose of buccal

fat pad, no edemafat pad, no edema Kwashiorkor; edema, potbelly, hair and Kwashiorkor; edema, potbelly, hair and

areas of skin are hypopigmented, hair is areas of skin are hypopigmented, hair is red, gray to white red, gray to white

KwashiorkorKwashiorkor

Africans call them Africans call them “Red Children”“Red Children” ““Flag Sign”; Flag Sign”; alternating bands of alternating bands of

pale and dark hair along a single pale and dark hair along a single strand correspond to periods of good strand correspond to periods of good and poor nutritionand poor nutrition

““Mosaic skin”; areas of Mosaic skin”; areas of hyper/hypopigmentation resemble hyper/hypopigmentation resemble peeling paint peeling paint

Carotenemia and Carotenemia and LycopenemiaLycopenemia

Excessive ingestion of : carrots, oranges, Excessive ingestion of : carrots, oranges, squash, spinach, turnips, corn, beans, butter, squash, spinach, turnips, corn, beans, butter, eggs, pumpkins, sweet potatoes, papayaeggs, pumpkins, sweet potatoes, papaya

Yellowish discoloration of skin, palms, soles, Yellowish discoloration of skin, palms, soles, central facecentral face

Carotenemia occurs in vegetariansCarotenemia occurs in vegetarians Lycopenemia; red foods, beets, tomatoes, Lycopenemia; red foods, beets, tomatoes,

chili beans (flatulence), berries leads to chili beans (flatulence), berries leads to reddish discoloration of skin aka “reddish discoloration of skin aka “K.C. K.C. Chiefs’ syndromeChiefs’ syndrome

Documents

Chronic Blistering Dermatoses Part 2 and Nutritional Diseases Adam Wray, D.O. May 9, 2006