Ichthyosis (plural ichthyoses) is a heterogeneous family disorder, mostly comprising of skin disorders of genetic origin. All types of ichthyosis have dry, thickened, scaly or flaky skin like fish.
Primary ichthyosis can be of following types
- Ichthyosis vulgaris
- Lamellar ichthyosis
- X-linked ichthyosis.
- Epidermolytic hyperkeratosis
- Congenital ichthyosiform erythroderma
Ichthyosis vulgaris is the mildest and most common form. It accounts for more than 95% of cases with an incidence of 1 case per 300 population.
Lamellar ichthyosis has an incidence of 1 case per 300,000 population and X-linked recessive ichthyosis 1 case per 6000 males.
Ichthyosis could be acquired also.
Types of Ichthyosis
Ichthyosis Vulgaris
It is inherited as an autosomal dominant character and thus, some other member of the family, especially one of the parents at least, should also manifest the disease. The lesions are usually not present at birth but develop during the first year of life.
Ichthyosis vulgaris is a skin problem that causes dry, dead skin cells to accumulate in patches on the surface of your skin. It is also known as fish scale disease.
An association between atopic dermatitis and this ichthyosis is noted.
These consist of dirty looking, brownish, angulated scales which are present all over the body but are most prominent on the anterior surfaces of the legs. Flexural surfaces of the joints such as the cubital and the popliteal fossae, axillae, groins and other skin folds are as a rule, not involved.
The face and the scalp are also not involved. Some patients, in addition, have a diffuse hyperkeratosis of the palms and the soles and occasionally, they may also have small asymptomatic micro-papules around the hair follicles.
The skin as a whole looks very dry. The lesions are worse during winter and improve during the summer months. There is some improvement in the condition at puberty, but otherwise, the abnormality persists throughout life. There are no symptoms, but it constitutes a profound cosmetic defect.
There may scaling on the eyelid skin and could lead to punctate epithelial keratitis and recurrent corneal erosion. Other ocular involvements are rare.
Ichthyosis Congenita
This is an uncommon but severe variant of lamellar ichthyosis. The child at birth is encased in a thick sheet of hyperkeratosis which shows deep fissures at the folds of skin.
Quite often, this state is not compatible with life and the child dies due to inability to take feeds or due to superadded infection.
Occasionally, however, the child may be able to shed the thick sheets of hyperkeratosis and then manifest the milder form of lamellar ichthyosis throughout the remaining life.
On histopathological examination, there is mild hyperkeratosis and a diminished granular layer in the epidermis. The dermis is normal.
Lamellar Ichthyosis
Lamellar ichthyosis is a rare, autosomal recessive, genetically heterogeneous skin disease caused by mutations involving multiple genetic loci.
This disease was previously called non-bullous variety of ichthyosiform erythroderma. It is inherited in an autosomal recessive way. Thus consanguineous marriages as between close relatives, are more likely to result in the manifestation of the disease even though other members of the family may be normal.
Children are covered at birth by a thickened membrane that subsequently is shed. The scaling of the skin involves the whole body with no sparing of the flexural creases.
Usually, the affected child shows diffuse erythema.
About 30% of the affected children develop cicatricial type bilateral ectropion. Secondary corneal ulceration may occur.
The skin looks shiny and shows fine wrinkles when pressed between the thumb and the index finger. The disease does not show any seasonal relationship but becomes less prominent as the age advances.
Biopsy shows massive, compact orthohyperkeratosis. There is variable degrees of parakeratosis and a markedly thick stratum corneum. The granular layer is either normal or increased.
X-linked Ichthyosis
This type of ichthyosis is transmitted by means of a recessive gene located on the distal short arm of the X-chromosome.
Thus, the disease is transmitted by females but manifested in the males.
It is based on the deficiency of an enzyme-steroid sulphatase in the cultured fibroblasts.
Clinically, the disease resembles ichthyosis vulgaris but the lesions are more profuse and involve a large part of the cubital and the popliteal fossae.
This scaling is most prominent over the extremities, neck, trunk, and buttocks. It may involve flexural cable but after The flexural creases may be involved but palms and soles are spared
The scales may extend even to the face. Comma-shaped corneal opacities developing at the adult stage and cryptorchidism may be associated and peculiar to this subtype.
Microscopically, there is an expanded stratum corneum without parakeratosis or acanthosis. The granular cell layer may be normal unlike vulgaris but could be absent in some cases where it poses a diagnostic difficulty.
Epidermolytic Hyperkeratosis
This type of ichthyosis, also known as bullous ichthyosis was earlier known as bullous variety of ichthyosiform erythroderma. Just after birth, the child shows bullous lesions and denuded areas with focal areas of hyperkeratosis.
As the child grows, the bullous lesions subside, but he/she develops more hyperkeratosis. The lesions are warty and more pronounced in the flexural folds with secondary infection and foul smell.
An underlying erythroderma in some cases and palmoplantar keratoderma may also be present. This disease is transmitted as an autosomal dominant trait but is extremely rare.
On biopsy examination, there is the presence of intracytoplasmic vacuoles in the granular layer and stratum spinosum. There and there is an increased number and size of keratohyaline granules, along with massive hyperkeratosis and a perivascular round cell infiltrate in the upper dermis.
Congenital Ichthyosiform Erythroderma
Congenital ichthyosiform erythroderma is a milder form of the disease and is autosomal recessive in inheritance.
It is caused by mutations in the genes coding for transglutaminase 1, 12R-lipoxygenase, and/or lipoxygenase 3.
Babies with lamellar ichthyosis, and congenital ichthyosiform erythroderma are referred to as collodion babies.
With growth, as children and adults, they show generalized red skin with thin, white scaling.
Persistent ectropion and scarring alopecia may be present.
The skin biopsy shows compact hyperkeratosis and a moderate increase in stratum corneum thickness. There is a normal or prominent granular layer.
Mild upper dermal lymphocytic infiltrate and prominence of blood vessels could be seen.
Acquired Ichthyosis
- Occurs in adults
- Small, white, fishlike scales on the extremities mainly but could be generalized.
- Seen in
- Malignancy – Hodgkin lymphoma, leukemia
- Systemic illness- Sarcoidosis, HIV infection, hypothyroidism, chronic hepatitis, etc
- Bone marrow transplantation
- Newborns with type 2 Gaucher disease
Associated Conditions
- Keratitis, ichthyosis, and deafness syndrome
- Hutchinson triad
- Notched, widely spaced peg teeth
- Interstitial keratitis
- Hearing loss and deafness
- Hutchinson triad
- CHIME
- Colobomas of the eye
- Heart defects
- Ichthyosiform dermatosis
- Mental retardation
- Netherton syndrome
- Autosomal recessive condition
- Ichthyosiform dermatosis with variable erythroderma
- Hair shaft defects
- Atopic features
- Sjögren-Larsson syndrome
- Autosomal recessive condition
- Ichthyosis
- Spastic diplegia
- Pigmentary retinopathy
- Mental retardation.
- CHILD [Congenital hemidysplasia with ichthyosiform erythroderma or nevus and limb defects]syndrome
- Rare X-linked dominant malformation syndrome
- Ichthyosiform erythroderma or nevi
- Ipsilateral limb defects
Clinical Presentation
Apart from scales which may appear at different periods depending on the type of ichthyosis, ocular features are most marked.
Some may be present in all types whereas others are specific.
- Eyelids
- Ectropion [the turning of the eyelid to out](lamellar ichthyosis)
- Blepharitis
- Trichiasis
- Absent eyelashes
- Absence of lacrimal puncta
- Keratinization and thickening of cornea secondary to ectropion
- Corneal
- Exposure keratitis and recurrent corneal erosion secondary to ectropion
- Band keratopathy
- Enlarged corneal nerves (common to all forms)
- Unilateral megalocornea ( seen in lamellar ichthyosis)
- Pre-Descemet membrane opacities ( seen in X-linked ichthyosis)
- Salzmann nodules on cornea (seen in ichthyosis vulgaris)
- Retina (see below)
- Coloboma (CHIME syndrome)
- Retinitis pigmentosa (Refsum disease)
- Maculopathy (Sjögren-Larsson syndrome)
Differential Diagnoses
- Acrodermatitis Enteropathica
- Acute Complications of Sarcoidosis
- Herpes Zoster
- Psoriasis
Diagnostic Work-up
Diagnosis involves histopathological studies, electron microscopy, and genetic studies to determine the type of ichthyosis.
Other lab tests, done as per requirement, are
- CBC and bone marrow aspiration to rule out leukemia, myelodysplastic syndromes
- Thyroid function tests
- Chest radiography (ie, sarcoidosis, lymphoma, HIV, tuberculosis)
- Serum antinuclear antibody
- Anti-double stranded DNA antibody
- Anti centromere antibody
- Anti-Scl-70 antibody (ie, systemic lupus erythematosus [SLE], systemic sclerosis)
Prenatal Diagnosis
- Intraamniotic fluid debris: In utero ultrasonography may be done for prenatal assessment.
- Low maternal serum unconjugated estriol during pregnancy can indicate placental STS deficiency and X-linked recessive ichthyosis.
- The FISH test may be done to know microdeletion of the STS gene for in X-linked ichthyosis.
- Prenatal direct mutational analysis of the keratinocyte transglutaminase gene may suggest a diagnosis of lamellar ichthyosis.
- Fetal skin biopsy
- examines keratinized hair canal
Treatment
The patients generally tend to apply oils, creams, petrolatum, and other similar household agents to counter the dryness, but the dryness and the scales continue to bother the patient. Glycerine being a hygroscopic agent helps in retaining the moisture in the skin and thus, has a better therapeutic effect.
This effect can be further enhanced by the addition of keratolytic agents such as salicylic acid or urea. Fiver percent salicylic acid in petrolatum or 10-40 percent urea in glycerine applied twice a day after the bath has been seen to revert the skin to a normal texture within two to three months.
It is, however, necessary to continue these applications for the rest of life. Urea and glycerine is a safer preparation. To reduce the stickiness of glycerine, a proportionate amount of water may be added to it for making the solution.
Local applications of retinoic acid and systemic administration of vitamin A is also used to reduce hyperkeratosis. Oral retinoids like Etretinate (1 mg/kg/d) and isotretinoin (2 mg/kg/d) have been shown to reduce scaling, discomfort, and disfigurement.
Local applications of emollients may also help in softening the keratotic sheets.
Severe cases, however, require treatment with corticosteroids in a dose of 10 mg prednisolone a day orally for a few months. For adults, treatment with corticosteroids is usually not required. Some cases have superadded infection with candida, and this should be treated with anti-fungal drugs.
For vesicular stage of epidermolytic ketraoses, local applications of one percent aqueous solution of gentian violet or brilliant green or any other antibiotic agent. For widespread or heavily infected lesions, systemic antibiotics should be used. In later stages, applications of emollients and keratolytic agents such as five percent salicylic acid in petrolatum or ten to 40 percent urea in glycerine may bring improvement.
For eyes, nonpreserved artificial tears and ointment to prevent dryness and exposure.
References
- Al-Akloby OM. Association of atopic dermatitis with primary hereditary ichthyoses. Saudi Med J. 2004 Aug. 25(8):1097-9.
- Banse-Kupin L, Pelachyk JM. Ichthyosiform sarcoidosis. Report of two cases and a review of the literature. J Am Acad Dermatol. 1987 Oct. 17(4):616-20.
- Cuevas-Covarrubias SA, Diaz-Zagoya JC, Rivera-Vega MR, et al. Higher prevalence of X-linked ichthyosis vs. ichthyosis vulgaris in Mexico. Int J Dermatol. 1999 Jul. 38(7):555-6.
- Shwayder T. Disorders of keratinization: diagnosis and management. Am J Clin Dermatol. 2004. 5(1):17-29.