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Icthyosis
- 1. ICHTHYOSI PRESENTER: DR ROHINI SONI MODERATOR: DR PASCHAL DSOUZA
- 2. ICHTHYOSIS ▸Derived from the Greek word ‘ichthys’, which means fish. ▸Heterogenous group of inherited disorders of epidermal differentiation featuring excessive scaling. ▸Due to altered cell kinetics of differentiation. ▸Excessive keratin buildup due to a desquamation defect, leading to retention of abnormally formed scale
- 3. TYPES OF ICHTHYOSIS NON‐SYNDR OMIC ICHTHYOSIS SYNDROMI C ICHTHYOSI S CONGENITAL ACQUIRED 1. MALIGNAN CIES 2. METABOLIC DISORDER S 3. CONNECTI VE TISSUE DISORDER S 4. INFECTION S 5. DRUGS
- 4. 2009. J Am Acad Dermatol 2010;63:607–41
- 5. 2009. J Am Acad Dermatol 2010;63:607–41
- 6. ICHTHYOSIS VULGARIS ▸Commonest and also the mildest form ▸Autosomal semidominant inheritance ▸Due to filaggrin mutations (FLG) ▸Results in impaired epidermal barrier formation and a marked reduction of natural moisturizing factors (NMF) which play a critical role in hydration of the stratum corneum
- 7. ▸Presents few months after birth to early childhood (3-12 months) ▸Mild itching, Xerosis Fine, white scales on extensor surfaces coarser on the lower extremities ▸Flexures spared ▸Hyperlinear palms/soles ▸Improves in summers ▸A/w Atopic diathesis keratosis pilaris
- 9. ‣ Laminated orthohyperkeratosis ‣ Markedly accentuated granular layer ‣ On electron microscopy :scarce and crumbly keratohyalin granules. HISTOLOGY
- 10. RECESSIVE X‐LINKED ICHTHYOSIS ▸2nd most common type of ichthyoses ▸X linked recessive ▸Involves extremities, trunk, neck; variable INVOLVEMENT of flexures ▸Sparing of palms/soles
- 11. Mother (with affected fetus): low/absent estrogen in urine/amniotic fluid → labor fails to progress → children are com
- 12. ▸Presents around infancy usually before 3 months of age with mild erythroderma and large translucent scales ▸Evolves into adherent brown “DIRTY” polygonal scales divided by wide splits ▸Associated with Comma-shaped corneal opacities Cryptorchidism Carcinoma of testis (↑risk)
- 13. INVESTIGATIONS ▸HISTOLOGY :hyperkeratosis or parakeratosis normal or slightly thickened granular layer ▸OTHER TESTS: serum lipoprotein electrophoresis (detects accumulation of cholesterol sulfate)
- 16. ▸Harlequin ichthyosis ▸Lamellar ichthyosis (LI) ▸Congenital ichthyosiform erythroderma (CIE) ▸Self‐healing collodion baby (SHCB) ▸Acral self‐healing collodion baby ▸Bathing suit ichthyosis (BSI)
- 17. HARLEQUIN ICHTHYOSIS ▸Most devastating type of ARCI . ▸Neonates are born with armour‐like skin (truncal plates with fissuring). ▸Impaired move- ment and the ability to drink and breath. ▸Bilateral ectropion and eclabium are present and hyperkeratotic skin may result in ears lacking retroaural folds. ▸Autoamputation of digits may occur.
- 19. Only 44% of children may survive. For those who survive, in later life persistent ectropion is a frequent major problem, and often these patients have problems achieving and maintaining normal body weight despite high‐calorie supple- mentation.
- 20. FEATURES ON HISTOLOGY ‣ Marked hyperkeratosis ‣ Parakeratoses ‣ Hypogranulosis Electron microscopy reveals numer- ous abnormal lamellar bodies in the stratum granulosum and accumulation of extruded irregular lamellar bodies as vesicular structures between the epidermal cornified cells.
- 21. LAMELLAR ICHTHYOSIS ▸AR ▸Presents AT BIRTH with collodion membrane encasing the baby which desquamates over the first 2-3 weeks ▸Usually thick large platelike dark (grayish- brown), quadrangular free at edges and adherent at CENTER ▸Flexural involvement ▸Tends to be largest at extremities separated by superficial fissuring arranged in a mosaic pattern resembling FISH SKIN Flexural involvement
- 22. Transglutaminase‐1 critically contributes to the the assembly of the cornified envelope by catalysing calcium‐dependent cross‐ linking of proteins, such as involucrin, loricrin and proline‐ rich proteins and by binding Ω‐hydroxy ceramides to proteins such as involucrin, thus connecting the lipid envelope with the CE
- 25. ASSOCIATIONS ▸NAIL ABNORMALITIES 1. dystrophy 2. nail fold inflammation 3. subungual hyperkeratosis 4. longitudinal or transverse stippling 5. grow 2-3 times the normal rate. ‣ Ectropion, eclabium, scarring alopecia, hypohidrosis, contractures heat intolerance (heat stroke), Involvement of palm and soles: Ranges from minimal hyper-linearity to severe PPK
- 26. ▸MASSIVE orthokeratotic hyperkeratosis ▸Normal or thickened granular layer ▸Acanthosis with increased mitoses ▸Perivascular lymphocytic infiltrate
- 27. CONGENITAL ICHTHYOSIFORM ERYTHRODERMA (CIE) ▸Mild erythema and generalized whitish desquamation ▸AR (some AD) ▸TGM1 gene, few ALOXE3 or ALOX12B gene mutation (encode lipoxygenase 3 and 12R-lipoxygenase, respectively) ▸Presents at birth with collodion membrane → generalized erythroderma and persistent fine white scaling ▸flexures involved ▸PPK ▸no improvement with age ▸Associated with scarring alopecia, ectropion, nail dystrophy (similar to LI but milder), heat intolerance, increased susceptibility to infections
- 28. COLLODION BABY ▸A number of forms of ichthyoses present at birth with infant encased in a glistening tight membrane of adherent keratinocytes, which has been compared to collodion ▸The membrane is then shed, leaving either normal skin (lamellar exfoliation of newborn) or, more often; ▸lamellar ichthyosis ▸Congenital Ichthyosiform Erythroderma ▸Bathing suit ichthyosis ▸X-linked recessive ichthyosis ▸neutral lipid storage disease ▸Gaucher's disease
- 29. BATHING SUIT ICHTHYOSIS ▸Peculiar type of ARCI ▸children are born as collodion babies later develop a lamellar type of ichthyosis that spares the face and the extremities, and follows the distribution pattern of bathing suits. ▸Due to peculiar missense mutations in TGM1that render the enzyme TG1 temperature ▸Shift of optimum temperature from 37C to 31C ▸Digital thermography validated a striking correlation between warmer body areas and the presence of scaling in patients ▸Aggravtes in summer
- 30. KERATINOPATHIC ICHTHYOSES EPIDERMOLYTIC ICHTHYOSIS ICHTHYOSIS BULLOSA SIEMENS ANNULAR EPIDERMOLYTIC ICHTHYOSIS CONGENITAL RETICULAR ICHTHYOSIFORM ERYTHRODERMA ICHTHYOSIS CURTH–MACKLIN
- 31. EPIDERMOLYTIC ICHTHYOSIS MUTATION IN KERATIN 1 &10 Environmental stress, Trauma,Hyperosmotic conditions Keratin aggregates (clumps around nucleus) Losing connections with desmosomes and hemidesmosomes EPIDERMOLYSIS Bullae formation due to seperation of keratinocyte
- 32. ▸AD ▸Presents at birth with initial erythroderma, bullae, denuded skin ▸Evolves into yellowish brown verrucous hyperkeratotic plaques most prominent over joints also scalp, neck and infra-gluteal folds, flexural involvement. ▸Involvement of warmer areas. Thus flexural predominance. ▸The older child and adult patients usually present with marked keratotic lichenification meaning rippled keratotic ridges
- 33. ▸On the knees and the lower legs, patients sometimes present with spiny hyperkeratosis ▸KRT10: mutations, the palms and soles are usually spared ▸KRT1: mutations usually have severe involvement of the palms and soles which can significantly impair walking ‣ Leads to A. recurrent infection B. sepsis C. dehydration & electrolyte imbalances due to compromised skin barrier D. failure to thrive
- 34. HISTOLOGY ▸ Massive orthokeratotic hyperkeratosis ▸ Hypergranulosis ▸ Granular and vacuolar degeneration of spinous and granular cell layers (EPIDERMOLYSIS)
- 35. ICHTHYOSIS BULLOSA SIEMENS ▸A variant of BCIE ▸AD ▸keratin 2e (K2) gene defect ▸Presents at birth with mild erythroderma and mild superficial blistering → evolves into brown hyperkeratotic plaques over joints, flexures, abdomen, dorsal hands and feet spares palms/soles ▸Keratosis is limited to the region around the navel and on the dorsal aspects of the hands and feet or the arm and the axillary region
- 36. ▸ Mauserung phenomenon (Mauserung is German for "moulting" and was first described by H.W.Siemens). ▸These are small patches of bare, apparently normal peeled skin
- 37. ANNULAR EPIDERMOLYTIC ICHTHYOSIS ▸Mild variant of EI ▸Shares a similar onset at birth, but later greatly improves ▸can feature bouts of disease activity associated with the development of numerous annular and polycyclic hyperkeratotic lesions especially on the trunk and extremities. ▸On histology : epidermoysis
- 38. CONGENITAL RETICULAR ICHTHYOSIFORM ERYTHRODERMA ▸AD ▸KRT10 mutations ▸Initially display generalized erythema and scaling with subsequent localized spontaneous healing which manifest with small pale white spots. ▸Ichthyosis en confettis
- 40. ▸AD ▸KRT 1 mutation ▸Extensive spiny hyperkeratosis (‘hystrix’‐like) covering the entire body and involving the palms and soles ▸Porcupine man
- 41. OTHERS: ERYTHROKERATODERMA VARIABILIS ‣ Migrating polycyclic erythematous lesions accompanied by hyperkeratosis ‣ Mutation in GJB3 gene encoding for connexins ‣ Fixed well‐demarcated keratotic and erythematous plaques, often bizarrely shaped, which show a predilection for extensor surfaces, lateral trunk and buttocks and extend and regress in area thickness and degree of erythema ‣ Transient erythematous, polycyclic or comma‐shaped macular lesions occurring at any site
- 43. CONRADI-HU ̈NERMANN-HAPPLE SYNDROME (CDPX2) ▸XD,only in females ▸At birth ▸Ichthyosiform erythroderma may be severe ▸CIE clears up after few months, lifelong hyperkeratosis distributed in linear, blotchy pattern, follicular atrophoderma ▸Discrete IV-like scaling ▸Patchy areas of cicatricial alopecia ▸Stippled calcifications of enchondral bone formation, chondrodysplasia punctata, short stature, asymmetric shortening of legs, kyphoscoliosis, dysplasia of hip joints, sectorial cataracts, asymmetric facial appearance as result of unilateral hypoplasia, flattened nose bridge
- 44. IFAP SYNDROME ▸ XR ▸ At birth ▸ Mild collodion skin, congenital atrichia ▸ Development of generalized follicular keratosis that can be severe or improves during first year of life ▸ Whitish scales with mild erythema ▸ SCALP :Follicular keratoses, atrichia, occasionally some sparse and thin hair may be present ▸ Severe photophobia, retarded psychomotor development: (cerebral atrophy, temporal lobe malformation, hypoplasia of corpus callosum), failure to thrive, atopic manifestations, inguinal hernia, aganglionic megacolon, testicular or renal anomalies
- 45. Photographs of patients with typical features of IFAP syndrome. Note: A) the atrichia, the photophobia, the cheilitis around the mouth, B) the ichthyotic scaling and erythematous and yellowish thick scaly hyperkeratotic plaques over the scalp, and C) the psoriasiform plaques over the buttocks.
- 46. Autosomal ichthyosis syndromes with prominent hair abnormalities Netherton Syndrome Ichthyosis Hypotrichosis Syndrome Ichthyosis Hypotrichosis Sclerosing Cholangitis
- 47. NETHERTON SYNDROME SPINK 5 MUTATION LETKI Deficiency (Serine protease inhibitor controls trypsin and chymotrypsin like enzyme activity) over‐desquamation of corneocytes and degradation of desmosomal proteins PAR 2 induction of PAR‐2 (protease‐activated receptor 2) related pro‐inflammatory responses
- 48. ▸AR ▸At birth (or later) ▸CIE in most of cases, collodion membrane rare, ILC, atopic dermatitis-like lesions ▸Fine or large, double-edged scales (ILC) ▸Short, fragile, and brittle hair; alopecia (Trichorrhexis invaginata) ▸Failure to thrive, severe atopic diathesis, increased IgE level and eosinophilia, frequent skin infections
- 49. IHS & IHSC ▸AR ▸At birth ▸LI, severe hypotrichosis, absent eyebrows and eyelashes Over time, scalp hair growth and appearance/color may improve ▸Brown colored coarse scales ▸Hypotrichosis in youth, sparse, unruly hair in adolescence, recessing frontal hairline in adults ▸Hair microscopy may reveal dysplastic hair, pili torti ▸IHSC : coarse thick hair, frontotemporal scarring alopecia; hypotrichosis, curly/woolly hair with sclerosing cholangitis or congenital paucity of bile ductsy
- 50. NEURO ICHTHYOTIC SYNDROMES REFSUM SYNDROME SLS MEDNIK CEDNIK GAUCHERS
- 51. REFSUM SYNDROME ▸AR ▸RD was found to be caused by inactivating mutations in PHYH encoding a human phytanoyl‐ CoA hydroxylase which is responsible for α oxidation of phytanic ▸Presents in late childhood. ▸Deteriorating vision due to retinitis pigmentosa and hearing, ataxia, neuropathy and usually mild ichthyosis.
- 55. APPROACH TO A PATIENT WITH ICHTHYOSIS
- 58. ▸Prenatal diagnosis of congenital ichthyosis is possible specially in Harlequin ichthyosis. ▸Amniocentesis , CVS, 3D/2D USG ▸ABCA12 gene analysis ▸USG shows abnormal protrusion on eye (ectropion), fixed open mouth and nasal hypoplasia
- 59. GENERAL CARE ▸Avoidance of strong drying soaps & use creamy soaps ▸Avoidance of unnecessary exposure to cold or hot climates potential for heat intolerance and heat stroke ▸Frequent showering (w/ immediate application of emollients) ▸Manual debridement of the collodion membrane is not recommended. ▸X-linked Ichthyosis: consultation with ophthalmologist (for corneal opacity) and surgeon (for cryptorchidism) is needed
- 60. LOCAL CARE ▸Emollients: Maintaining hydration–creams and ointments (Vaseline, liquid paraffin, glycerin, olive oil). These agents should be applied immediately after washing with water, without allowing skin to dry ▸Humectants: (10-30%) Topical urea, 40% to 60% solution of propylene glycol in water (usually under an occlusive suits)– Drawbacks: renal failure and cardiac toxicity when given systemically. ▸Keratolytics: Salicylic acid and lactic acid; (salicylic acid products are best reserved for localized resistant thicker areas)
- 61. ▸Topical retinoids: (retinoic acids, tazarotene) ▸Calcipotriol ▸Topical Antibiotics: applied to fissures ▸Antiseptics: can be used topically to control odor (as well as antimicrobials)
- 62. SYSTEMIC ▸Systemic retinoids: (Isotretinoin or Acitretin) reserved for severe disease that is refractory to conventional therapy Lamellae Ichthyosis and Nonbullous congenital ichthyosiform erythroderma ▸Systemic retinoids may be helpful, but long-term use problematic ▸Epidermolytic Hyperkeratosis: Systemic retinoids help with keratoses but may increase tendency to blister ▸Oral antibiotics: for infections
- 63. TREATMENT OF ASSOCIATED SYMPTOMS ▸ECTROPION: Surgical correction ▸EARS: cleaning of external ear cannal every 4 weeks esp in BSI ▸HYPOHYDROSIS: Oral retinoids ▸MUSCULOSKELETAL PROBLEMS Physiotherapy for flexural contractures ▸VITAMIN D SUPPLEMENTS esp in lamellar and CIE
- 64. GENE THERAPY ▸In the case of dominant negative gene mutations, such as in EHK, it is possible to silence a mutated keratin allele by applying RNAi technology. ▸It is hoped that some encouraging in vitro results will soon lead to clinical trials. ▸In the case of recessive disorders where an enzyme or transporter protein is missing, the principle of ex vivo gene transfer using cultured keratinocytes that are re-transplanted to the patient.
- 65. THANK YOU