DCNP - Systemic Diseases, Genodermatoses, Granulomatous & Neutrophilic Disorders Flashcards
ichthyosis
Family of skin disorders of cornification characterized by scaling with various severity* Most are hereditary and present at birth or shortly after* There are some acquired which may be associated with underlying nutritionaldeficiency, malignancy, infection, autoimmune disorders or unknown etiology* Pathogenesis from increased cohesiveness, abnormal proliferation and keratinization* Most common types of ichthyosis are ichthyosis vulgaris and x-linked ichthyosis
ichthyosis vulgaris
Most common type
Mutation in filaggrin gene, semi-dominant (incomplete penetrance)
Not present at birth, onset in infancy or childhood association with atopic triad and keratosis pilaris
Occlusive agents - prevent evaporation reduce transepidermal water loss
Petrolatum, vegetable oils; sterols (ceramides); wax esters, animal fats (lanolin); silicones (dimethicone); and, hydrocarbons (mineral oil, petrolatum). Humectants- attract and bind water (best when used in combination with occlusive moisturizer)
Urea (also promotes desquamation of corneocytes & incr. penetration of topical medications). Helps with itch
Alpha-hydroxy acids
Glycerin- can also help with barrier repair
Hyaluronic acid
Propylene glycol
Honey
x-linked recessive ichthyosis
Mutation of STS gene, loss of steroid sulfatase* A deficiency in STS means that cholesterol sulfate accumulates in the stratum corneumand prevents proteases that degrade corneodesmosomes >impaired desquamationleading to increased corneocyte cohesion and retention* Male offspring of asymptomatic carrier mother
Usually presents in neonatal period with fine scale and generalized peeling* Larger plate-like scale in adults, sparing antecubital fossa, popliteal areas and face, butaffects axillae and neck (“dirty neck” appearance). Also spares palms and soles* Higher risk of cryptorchidism and testicular cancer. Less commonly neurologic,development and cognitive abnormalities.* Higher risk of asymptomatic corneal opacities in 50% adults* Increased risk of atopic dermatitis
If mother is carrier, the risk of disorder:** 25% healthy boy* 25% boy with disease* 25% healthy girl* 25% girl carrier w/o disease
can be detected prenatally during serum screening for Downs syndrome (elevatedserum estriol)
Skin care similar to IV above including exfoliation* Avoid overheating (thick scale impedes normal sweating)* Adults with severe disease, consider systemic retinoids (off label) including isotretinoinand acitretin.o MOA- anti-keratinizing properties, modulation of keratinocyte proliferation &differentiation* Also, topical retinoids like tazarotene
palmoplantar keratodermas
Group of inherited or acquired, considerable clinical and genetic heterogeneity* Non-syndromic and syndromic* Excessive epidermal thickening
Diffuse, focal, striate or punctate* Presence/absence of transgrediens hyperkeratosis (contiguous extension ofhyperkeratosis beyond the palmar and/or plantar skin)* Characteristics of hyperkeratosis (desquamative, fissures, waxy, large/small)* Presence of palmoplantar hyperhidrosis* Pain* Involvement hair, nails or mucosa surfaces* Extracutaneous findings (ophthalmology, MS, renal, ENT, etc.)
Regular bathing and exfoliation regularly* Multidisciplinary approach (i.e. podiatry)* Prevention of secondary infections* If painful or disability, like inherited pachyonychia congenita, address the thickness ofnails and lesions (keratolytics, exfoliants, paring, etc.)* Footwear and foot care, orthotics, assistive devices* Hand care, and prevention of trauma and infection* Oral hygiene if teeth are involved.* Topical therapieso Softening skin w/keratolytics- urea, lactic acid, salicylic acid, propylene glycolo Exfoliative- keratolytics w/higher % like urea 20-40% and combinationso Topical retinoids off-label- tazarotene (o.o5% or o.1% cr) or tretinoino Caution in children d/t systemic absorptions* Systemico Retinoids off-label- acitretin and isotretinoin (gain control and taper off)
neurofibromatosis type 1
Autosomal dominant* Cutaneous, neurologic, skeletal and ocular tumors (benign & malignant)* Mutation in NF1 gene* The majority of individuals can be diagnosed by age 3 yrsNIH diagnostic criteria for NF1Includes at least two of the following features:1) ≥ 6 café -au-lait macules (with largest diameter >0.5cm in prepubertal individuals or>1.5cm in post-pubertal individuals,2) axillary or inguinal freckling (Crowe sign),3) ≥ 2 neurofibromas (any type) or one plexiform neurofibroma,4) ≥ 2 more iris hamartomas (Lisch nodules),5) distinctive bony lesion (i.e. sphenoid wing dysplasia or long bone cortical thinning w/ orw/o pseudoarthrosis6) a first degree relative with NF1
Genetic testing is indicated for prenatal testing, preimplantation genetic diagnosis, andfor confirmation in individuals with suspected NF1* Annual physical exams incl. fundoscopic until age 7 yrs* Monitor for malignant peripheral nerve sheath tumors which can metastasis (routineimaging not recommended)* Risks: optic gliomas, cognitive deficits/learning disabilities, epilepsy, MPNST (10%lifetime risk), cosmetic deformities from dermal and plexiform neurofibromas,neurologic deficits. Other complications based on involvement of organs. Othermalignancies.Management* Referral to multidisciplinary team of specialists.* Off-label and investigational tx with thalidomide, VEGFR inhibitors, tipifarnib, rapamycin
neurofibromatosis type 2
Autosomal dominant* Cutaneous, neurologic, skeletal and oculartumors (benign & malignant)* Mutation in NF2 gene* The majority of individuals can be diagnosed byage 3 yrs BUT is usually delayed (not recognized).Most are dx in 2nd decade of life
Schwannomas are nerve sheathtumors arising in the cranialnerves, spinal roots or peripheralnerves.
Cutaneous tumors: schwannomas and neurofibromaso Plaques (+/- hyperpigmented and sometimes w/terminal hairs); subcutaneousnodules along the nerve sheatho Neurofibromas similar to patients with NF1 (many are actually schwannomas)* Unilateral hearing loss, +/- tinnitus, and problems with balance* Mononeuropathy (usually facial nerve like Bell’s palsy symptoms)* Malignant transformation of schwannomas into malignant peripheral nerve sheathtumors (10-fold higher if history of radiation therapy)* CNS tumors (most common are meningiomas and often multiple)* Ophthalmologic abnormalities (cataracts, optic nerve meningiomas and hamartomas)* Diagnosis requires one of following:o Bilateral acoustic neuromasOro First degree relative with NF2 plus, either:▪ Unilateral eight nerve mass or▪ Two neurofibromas, schwannomas, optic glioma, meningioma, posteriorsubcapsular opacity.
tuberous sclerosis
Mutation TSC1 or TSC2, autosomal dominant (rare to be De novo), highly variableexpression* Neurocutaneous disorder involving multiple systems* Named after the appearance of cerebral cortical lesions* Tuberous Sclerosis Alliance organization’s diagnostic criteriao 2 major or 1 major + 2 minor features
MajorFacial angiofibromas or forehead plaque,nontraumatic ungual or periungual fibroma,≥ 3 hypomelanotic macules (‘ash leaf spots’),connective tissue nevus (‘Shagreen patch’),multiple retinal nodular hamartomas,cortical tuber, subependymal nodule, giantcell astrocytoma, single or multiple cardiacrhabdomyoma, lymphangioleiomyomatosis,and renal angiomyolipoma
MinorMultiple dental enamel pits, hamartomatousrectal polyps,bone cysts, cerebral white matter radialmigration lines, gingivalfibromas, nonrenal hamartomas, retinalachromic patch, cutaneoussymmetric hypopigmented macules(‘confetti’ macules), and multiplerenal cysts
Ash-leaf spots- hypopigmented macules* Angiofibromas –bilateral face* Shagreen patches- connective tissue nevi. Usually on lowertrunk* Forehead fibrous plaques- yellowish/tan plaques (samehistology as angiofibromas)* Ungual fibromas- adjacent or under nail plate* Extracutaneous- brain lesions, dental abnormalities,cardiac, ocular, pulmonary, hepatic and renalmanifestations
Angiofibromas (usu. appearing around 5 yrs old)- destructive lasers)* Genetic testing & counseling (esp. perinatal to prepare for immediate neonatalassessment and treatment* Multidisciplinary approach, especially neurology* Screening family
ehlers-danlos syndrome
Group of genetic disorders characterized by defect in collagen synthesis & metabolism* Characterized by: hyperextensibility, joint mobility & tissue fragility
Multidisciplinary approach coordinated by PCP* Genetic testing counseling based upon the type of EDS Pregnancy and fertilitycounseling* Early recognition of symptoms* Education and prevention of skin fragility, wound healing and easy bruising* Joint protection and function but also address musculoskeletal pain* Physical therapy* Patient education and psychosocial support* Recommend urgent referral if:* Sudden onset of pain, bleeding, dyspnea, chest pain, visual loss, orthostatic hypotension
DARIER’S DISEASE (Darier White or keratosis follicularis)
Autosomal dominant; M=F; onset puberty; chronic* Mutation ATP2A with variable expression* Histology is acantholysis and dyskeratosis
Keratotic, red/brown, papules coalescing into plaques* Crusted and greasy characteristics; malodorous* Favors seborrheic dermatitis distribution; worse insummer or humidity* Nails have longitudinal redness and ridging and “v”shaped nicking and distal edge* Secondary infections are common
Genetic and fertility counseling* Light weight clothing and avoid humidityTopicalso Retinoids (off-label)o Antibacterial washes, emollients, topical antifungalso Corticosteroids (incr. risk for secondary infection)Systemicso Retinoids (acitretin or isotretinoin-both off-label) with appropriate monitoringDestructive methodso Laser, surgical, dermabrasion
Hailey-Hailey
Autosomal dominant, mutation of ATP2C1* Also called benign familial pemphigus* Chronic and relapsingClinical Presentation* Blisters (flaccid), erosions, maceration of flexural area with erythema* Involving intertriginous areas (clinical appearance similar to intertrigo)* Worsened by friction or pressure* High risk for secondary infections* Can develop crusting and malodorous* Wax and waneManagement* Avoidance of heat, moisture and friction (loose clothing)* Weight loss
Bleach baths or chlorhexidine washes to decrease colonization* First-line:o Topical anti-bacterials if needed: clindamycin 1%, gentamycin 0.1% or mupirocin2% for 2-4 weekso Topical ketoconazole 2% cream for suspected secondary fungal infectionso Topical corticosteroids- short course of mid- to high potency for flareo Topical calcineurin inhibitor, tacrolimus 0.1 (off-label), for long term use* Second-line for severe diseaseo Oral anti-bacterials or antifungals guided by cultures and sensitivitieso Botulinum toxin type A (off-label) for excessive sweating that trigger thesymptomso Severe disease: consider CsA, Mtx, acitretino Only as last option, destructive methods including surgical excision, CO2 laser
xanthomas/xanthelasma
Xanthelasma is most common type* Deposition of lipids in the skin* Usually Fhx hyperlipidemia or other factors contributing to dyslipidemiaClinical Presentation* Yellowish flat papules/plaques most often upper eyelids (trunk, neck, axillae)* Between digits (esp. 1st/2nd) hallmark for familial hypercholesterolemia* Rare subtype diffuse symmetrical eruption w/o dyslipidemia> ?hematologic DOs
Address underlying conditions included lipid lower tx (may improve)* Cosmetic destruction:o Trichloroacetic acid 70%o Cryotherapyo CO2 or Q-switched Nd:YAG laser**does not prevent recurrence
Postherpetic neuralgia
Reactivation of latent varicella zoster virus in somatic sensory* ≥ 4 months after resolution of skin eruption* Usually precede by nonspecific symptoms (fever, malaise)* Post-herpetic itch more often in facial than truncal distribution* Sharp, burning, stabbing pain; constant or intermittent* Treatment-o First-line: gabapentin or pregabalin (except if renal insufficiency)o Mild- topical capsaicin or lidocaine for short term reliefo Moderate/severe: carbamazepine, antidepressants amitriptyline, desipramine,fluoxetine or paroxetine
Notalgia paresthetica
Usually from vertebral column disease or may be trauma, DM or endocrine neoplasia* Circumscribed area of back, usu. scapular border midback, hyperpigmentation* Treatment- capsaicin cr or patches, gabapentin, TCAs or botulinum toxin Type Ainjections
Brachioradial pruritus
Spinal cord or cervical radiculopathies (i.e. spinal stenosis)* Dorsolateral forearm-corresponding C5/6 (+/- shoulders)* Itching, burning, tingling* “ice pack sign” symptoms worsen w/heat and improve with cold* Treatment- topical capsaicin, gabapentin, fluoxetine, amitriptyline, doxepin
Neuropathic anogenital pruritus
High suspicion if no primary rash* 80% have underlying lumbar radiculopathy (nerve/root compression)* Treatment similar tx as above and steroid or lidocaine nerve block