AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Hereditary ichthyosis vulgaris and acquired ichthyosis vulgaris, members of a group of cutaneous disorders of keratinization, appear similar both clinically and histologically. The term ichthyosis is derived from the ancient Greek root ichthys, meaning fish. Although the resemblance is rather fanciful, it nevertheless conveys the characteristic features of these diseases. References to ichthyosis have been found in ancient medical texts aged more than 2000 years. Robert Wilan first made the most accurate description of ichthyosis in the English literature in 1808. Later modifications classified the diseases into hereditary and acquired forms.

Hereditary ichthyosis vulgaris is an autosomal dominant genetic disorder first evident in early childhood. It is the most common form of ichthyosis, accounting for more than 95% of ichthyosis cases. It is caused by altered profilaggrin expression leading to scaling and desquamation. Visible scales are retained for longer periods and sloughed off in clumps. Hereditary ichthyosis is also associated with atopy. The protein filaggrin is important in maintaining effective skin barrier function. Loss-of-function mutations in the profilaggrin gene (FLG) are evident in up to 10% of the population, causing ichthyosis vulgaris and representing a major risk factor for the development of atopic dermatitis.¹

Acquired ichthyosis, usually appearing for the first time in adulthood, is a nonhereditary condition associated with internal disease. Acquired ichthyosis is rare and must be viewed as a marker of systemic disease, including malignancy. Cases have been attributed to the use of certain medications.

Other eMedicine articles on ichthyosis include the following:

• Ichthyosis Fetalis
• Ichthyosis Vulgaris, Hereditary and Acquired
• Ichthyosis, Lamellar
• Ichthyosis (ophthalmology focus)

Pathophysiology

Ichthyosis vulgaris is classified as a retention hyperkeratosis. The only known molecular marker affected by hereditary ichthyosis vulgaris is profilaggrin, a high molecular weight filaggrin precursor. Profilaggrin, synthesized in the granular layer of the epidermis, is a major component of keratohyalin granules. Through various posttranslational modifications, profilaggrin is converted to filaggrin, which aggregates keratin intermediate filaments in the lower stratum corneum. Filaggrin is proteolyzed and metabolized, producing free amino acids that may play a critical role as water-binding compounds in the upper stratum corneum. Normal cycles of skin hydration and dehydration contribute to normal desquamation.  These cycles are disrupted in ichthyosis vulgaris.

Normal expression of the profilaggrin gene can be first detected in the granular layer. In ichthyosis vulgaris, the expression of profilaggrin is absent or reduced in the epidermis. This biochemical abnormality correlates with the decreased numbers of keratohyalin granules and the clinical severity of the condition. Analyses of cultured keratinocytes have shown reduced profilaggrin mRNA. Compared with normal amounts, one study found only 50% of the profilaggrin mRNA and 10% of the profilaggrin protein present. Research has shown that defective posttranscriptional regulation leads to decreased stability of profilaggrin mRNA.

The profilaggrin gene is part of a cluster of genes on 1q21 that encodes for structural proteins expressed in terminally differentiating epidermis. This complex, called the epidermal differentiation complex, involves many genes involved in this process. An adjacent region on 1q22 may also be involved. The underlying molecular mechanisms contributing to the pathophysiology of this disease have not yet been determined. Studies are currently underway in humans and mouse models.

Two common filaggrin (FLG) null mutations cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. Comprehensive analysis of the gene encoding filaggrin uncovered prevalent and rare mutations in ichthyosis vulgaris and atopic eczema.² These common European mutations are ancestral variants carried on conserved haplotypes. Fifteen variants were described, including 7 that are prevalent, all being either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis.

Filaggrin mutations p.R501X and c.2282del4 were analyzed in patients with ichthyosis vulgaris.³ Homozygotes and compound heterozygotes may be severely affected, whereas heterozygotes showed mild disease or were asymptomatic, suggesting semidominant inheritance with incomplete penetrance in heterozygotes. The presence of FLG mutations in 15 of 21 ichthyosis vulgaris patients were studied with a marked generalized scaling phenotype, including 8 affected members of a 4-generation family. In this group, heterozygous patients for p.R501X and c.2282del4 also displayed a pronounced phenotype.

Mutations in the gene encoding filaggrin have been identified as the cause of ichthyosis vulgaris and shown to be major predisposing factors for atopic dermatitis both in European and Japanese populations.^{4, 5}

Frequency

United States

Hereditary ichthyosis vulgaris is a common disease in the United States, with a prevalence of approximately 1 case in 300 persons. Because symptoms improve with age, the true prevalence is probably higher. Acquired ichthyosis is extremely rare. Its prevalence in the United States is unknown.

International

Hereditary ichthyosis vulgaris is found worldwide, and the prevalence depends on the location. One study in Berkshire, England, observed a frequency of 1 case in 250 schoolchildren. Acquired ichthyosis is extremely rare. Its prevalence worldwide is unknown.

Mortality/Morbidity

• Children and adolescents with hereditary ichthyosis vulgaris may experience some morbidity in terms of cosmesis. Secondary infections may occur in fissures of the hands and feet.
• The morbidity and mortality of acquired ichthyosis in adults is due to associated internal disease.

Race

• Hereditary and acquired ichthyosis vulgaris have no known racial predisposition.

Sex

• Hereditary and acquired ichthyosis occur equally in men and women.

Age

• Hereditary ichthyosis vulgaris typically is absent at birth. It appears in most patients during the first year of life and in the vast majority by age 5 years. The extent of scaling usually intensifies up until puberty and subsequently decreases with age.
• Acquired ichthyosis usually first appears in adulthood; however, age-associated systemic diseases do occur in children.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• Although the skin in hereditary ichthyosis vulgaris looks and feels normal at birth, it gradually becomes rough and dry in early childhood.
• • Scaling tends to be most prominent on the extensor surfaces of the extremities and absent on the flexor surfaces.
  • The diaper area is usually unaffected.
  • The forehead and cheeks may be involved early on, but scaling usually diminishes in these areas with age.
  • A notable amelioration of symptoms occurs during the summer months.
  • A family history of hereditary ichthyosis vulgaris may be difficult to ascertain because of the varying degrees of penetrance and the general improvement of symptoms over time.
  • Many hereditary ichthyosis vulgaris patients have associated atopic manifestations (eg, asthma, eczema, hay fever). Atopic conditions can be found in many family members, with or without symptoms of ichthyosis vulgaris. One study noted atopic manifestations in almost half of all subjects enrolled, with 41% having at least one relative who also was affected.
• Acquired ichthyosis is clinically indistinguishable from hereditary ichthyosis; however, acquired ichthyosis is associated with various systemic diseases.
• • The appearance of ichthyosis in adulthood can occur before or after the diagnosis of a systemic condition.
  • Disease severity varies depending on the course of the associated systemic condition.
  • Acquired ichthyosis is associated with many systemic diseases, including cancer (especially lymphoma), sarcoidosis, leprosy, thyroid disease, hyperparathyroidism, nutritional disorders, chronic renal failure, bone marrow transplantation,⁶ and HIV infection.⁷ Autoimmune diseases, including systemic lupus erythematosus⁸ and dermatomyositis,⁹ are also linked. It was recently described in a patient with the overlap syndrome consisting of systemic sclerosis and systemic lupus erythematosus.⁸
  • The types of cancers most often found in association with acquired ichthyosis are Hodgkin disease, non-Hodgkin lymphoma (including mycosis fungoides), myeloma, Kaposi sarcoma, leiomyosarcoma, and carcinomas of the lung, breast, ovary,¹⁰ and cervix.¹¹
  • The use of certain medications has been linked to acquired ichthyosis, namely nicotinic acid,^{12, 13} triparanol, butyrophenones, dixyrazine,¹⁴ cimetidine, and clofazimine.¹⁵
  • Bathing suit ichthyosis is a striking and unique clinical form of autosomal recessive congenital ichthyosis characterized by marked scaling on the bathing suit areas but sparing of the extremities and the central face. Bathing suit ichthyosis, caused by transglutaminase-1 deficiency, displays evidence that suggests it is a temperature-sensitive phenotype.¹⁶

Physical

• Ichthyosis vulgaris (both hereditary and acquired) is characterized by symmetrical scaling of the skin, which varies from barely visible roughness and dryness to strong horny plates.
• • Scales are small, fine, irregular, and polygonal in shape, often curling up at the edges to give the skin a rough feel.
  • Scales vary in size from 1 mm to 1 cm in diameter and range from white to dirty gray to brown. Dark-skinned individuals often have darker scales.
  • Different types of scaling may be found in different areas, even in the same patient.
  • Most scaling occurs on the extensor surfaces of the extremities, with a sharp demarcation between normal flexural folds and the surrounding affected areas.
  • The lower extremities generally are more affected than the upper extremities. Compared to other sites, the scales overlying the shins are thicker, darker, and arranged in a mosaic pattern. Patients often report "lizard skin" in these areas during the winter.
  • If the trunk is involved, scaling tends to be more pronounced on the back than on the abdomen.
  • Relative sparing of the face is seen, most likely because of increased sebaceous secretions, although the cheeks and forehead may be involved during early childhood in the hereditary form.
  • Dry scaling is often observed uniformly over the scalp.
  • Sparing of the flexural folds (eg, neck, axillae, antecubital and popliteal fossae) is attributed to the relative increase in temperature and humidity in these areas.
  • Overall symptoms of ichthyosis vulgaris generally improve in the summer months or in warm climates.
• Hyperkeratosis is often present on the palms and soles, causing them to appear dirty.
• • Skin creases in these areas are more prominent and can lead to painful fissuring, especially during dry weather.
  • Secondary infections at fissure sites are common.
• Keratosis pilaris (follicular hyperkeratosis) occurs on the side of the cheek and neck, dorsum of the upper arms, buttocks, and thighs.
• • It consists of spiny parafollicular papules that when palpated resemble a cheese grater.
  • Dried skin in the central portion is often white and mistaken for pus.
  • Inflammation may or may not be present.
  • Keratosis pilaris, which can be present without scaling, may be the only finding in family members with hereditary ichthyosis vulgaris.
• Pruritus can be caused by dry skin, even if inflammation is not evident. As a result, itching and scratching may lead to erythema in affected areas.

Causes

• Hereditary ichthyosis vulgaris is an autosomal dominant genetic disorder first evident in early childhood.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Xerosis
Ichthyosiform sarcoid¹⁷

WORKUP

Section 5 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
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Procedures

Skin biopsy specimens can be examined under light microscopy and electron microscopy. Take biopsy samples from regions of maximal hyperkeratosis because areas of mild scaling are less reliable for histopathologic analysis and findings may be indistinguishable from those of normal skin. The thickest scales are usually found on the anterior aspect of the lower leg.

Histologic Findings

The histological appearance of both hereditary ichthyosis and acquired ichthyosis is practically identical. The stratum corneum shows compact hyperkeratosis, although some areas can be laminated. Follicular plugging may be present and represents associated keratosis pilaris. The granular layer is usually one-layer thick or absent. Ichthyosiform sarcoid, a manifestation of acquired ichthyosis in sarcoid patients, has the additional presence of multiple noncaseating granulomas in the dermis.

Ultrastructural studies show reduced or absent keratohyalin granules housed in the granular layer. They appear spongy or crumbly, most likely due to defective keratohyalin synthesis. The hyperkeratotic portions of the stratum corneum have a normal keratin pattern.

TREATMENT

Section 6 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Hereditary ichthyosis vulgaris is a chronic disorder that may improve with age but often requires continuous therapy. The severity of acquired ichthyosis usually depends on the status of the underlying systemic condition. The main approach to treatment of both conditions includes hydration of the skin and application of an ointment to prevent evaporation. Hydration promotes desquamation by increasing hydrolytic enzyme activity and the susceptibility to mechanical forces. Pliability of the stratum corneum is also improved.

• Topical retinoids are helpful for some patients.
• Alpha-hydroxy acids (eg, lactic, glycolic, or pyruvic acids) are effective for hydrating the skin. They work by causing disaggregation of corneocytes in the lower levels of the newly forming stratum corneum. Lactic acid is available as a 12% ammonium lactate lotion, or it can be compounded by prescription in a concentration of 5-10% in a suitable vehicle. Twice-daily applications have shown to be superior to petrolatum-based creams for controlling of ichthyosis vulgaris.
• Removal of scales can be aided by keratolytics (eg, salicylic acid), which induce corneocyte disaggregation in the upper stratum corneum. A commercially available 6% salicylic acid gel can be used on limited areas.
• Over-the-counter products often contain urea or propylene glycol. Moisturizers containing urea in lower strengths (10-20%) produce a more pliable stratum corneum by acting as a humectant. Propylene glycol draws water through the stratum corneum by establishing a water gradient. Thick skin is then shed following hydration. Propylene glycol is a common vehicle in both prescription and over-the-counter preparations.
• Topical retinoids (eg, tretinoin) may be beneficial. They reduce cohesiveness of epithelial cells, stimulate mitosis and turnover, and suppress keratin synthesis.¹⁸ Tazarotene, a topical receptor-selective retinoid, has also been effective in one small trial.¹⁹
• Ichthyosis vulgaris is not responsive to steroids, but a mild topical steroid may be useful for pruritus.
• Acquired ichthyosis vulgaris generally tends to improve with treatment of the underlying systemic condition.

MEDICATION

Section 7 of 11  

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• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Retinoids

Decrease cohesiveness of abnormal hyperproliferative keratinocytes and may reduce potential for malignant degeneration. Modulate keratinocyte differentiation. Have been shown to reduce risk of skin cancer formation in renal transplant patients.

Drug Category: Humectants

Increase skin moisture.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Deterrence/Prevention

• In many patients, scaling can be controlled by diligent and consistent treatment.

Complications

• The extremities may fissure and become secondarily infected.
• Additional complications in acquired ichthyosis depend on the associated systemic disease.

Prognosis

• The prognosis for hereditary ichthyosis vulgaris is excellent. Many patients experience improvement of symptoms with age.
• The prognosis for acquired ichthyosis vulgaris depends on the severity of the underlying systemic disease.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to include a thorough examination of the patient for associated systemic disease (especially malignancy) in the diagnosis of acquired ichthyosis: Acquired ichthyosis overwhelmingly occurs in older patients who are generally more susceptible to cancer; this does not imply that acquired ichthyosis cannot occur in younger patients.
• Failure to consider internal disease in all cases of new-onset ichthyosis vulgaris: This may lead to additional morbidity and mortality as a result of the progression of the underlying disease

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Hereditary ichthyosis vulgaris with thick scaling of the anterior shins.
	View Full Size Image
Media type:  Photo

Media file 2:  Hematoxylin and eosin staining of acquired ichthyosis vulgaris in an adult. Shows epidermal atrophy with thinning of the granular layer. No dermal infiltrate is evident.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
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• References

1. McGrath JA, Uitto J. The filaggrin story: novel insights into skin-barrier function and disease. Trends Mol Med. Jan 2008;14(1):20-7. [Medline].
2. Sandilands A, Terron-Kwiatkowski A, Hull PR, O'regan GM, Clayton TH, Watson RM, et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet. May 2007;39(5):650-4. [Medline].
3. Gruber R, Janecke AR, Fauth C, Utermann G, Fritsch PO, Schmuth M. Filaggrin mutations p.R501X and c.2282del4 in ichthyosis vulgaris. Eur J Hum Genet. Feb 2007;15(2):179-84. [Medline].
4. Nomura T, Sandilands A, Akiyama M, Liao H, Evans AT, Sakai K, et al. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol. Feb 2007;119(2):434-40. [Medline].
5. Nomura T, Akiyama M, Sandilands A, Nemoto-Hasebe I, Sakai K, Nagasaki A, et al. Specific Filaggrin Mutations Cause Ichthyosis Vulgaris and Are Significantly Associated with Atopic Dermatitis in Japan. J Invest Dermatol. Jan 17 2008;[Medline].
6. Spelman LJ, Strutton GM, Robertson IM, Weedon D. Acquired ichthyosis in bone marrow transplant recipients. J Am Acad Dermatol. Jul 1996;35(1):17-20. [Medline].
7. Kaplan MH, Sadick NS, McNutt NS, Talmor M, Coronesi M, Hall WW. Acquired ichthyosis in concomitant HIV-1 and HTLV-II infection: a new association with intravenous drug abuse. J Am Acad Dermatol. Nov 1993;29(5 Pt 1):701-8. [Medline].
8. Lee HW, Ahn SJ, Choi JC, Chang SE, Choi JH, Moon KC, et al. Acquired ichthyosis associated with an overlap syndrome of systemic sclerosis and systemic lupus erythematosus. J Dermatol. Jan 2006;33(1):52-4. [Medline].
9. Urrutia S, Vazquez F, Requena L, Sanchez Yus E. Acquired ichthyosis associated with dermatomyositis. J Am Acad Dermatol. Mar 1987;16(3 Pt 1):627-9. [Medline].
10. Roselino AM, Souza CS, Andrade JM, Tone LG, Soares FA, Llorach-Velludo MA, et al. Dermatomyositis and acquired ichthyosis as paraneoplastic manifestations of ovarian tumor. Int J Dermatol. Aug 1997;36(8):611-4. [Medline].
11. Ennibi K, Rabhi M, Al Bouzidi A, Bahrouch L, Boudlal M, Zinebi A, et al. [Acquired ichthyosis revealing an Hodgkin's disease.]. Rev Med Interne. Jan 21 2008;[Medline].
12. Parsons WB Jr, Flinn JH. Reduction of serum cholesterol levels and beta-lipoprotein cholesterol levels by nicotinic acid. AMA Arch Intern Med. May 1959;103(5):783-90. [Medline].
13. Williams ML, Feingold KR, Grubauer G, Elias PM. Ichthyosis induced by cholesterol-lowering drugs. Implications for epidermal cholesterol homeostasis. Arch Dermatol. Nov 1987;123(11):1535-8. [Medline].
14. Poulsen J. Hair loss, depigmentation of hair, ichthyosis, and blepharoconjunctivitis produced by dixyrazine. Acta Derm Venereol. 1981;61(1):85-8. [Medline].
15. Caver CV. Clofazimine-induced ichthyosis and its treatment. Cutis. Apr 1982;29(4):341-3. [Medline].
16. Oji V, Hautier JM, Ahvazi B, Hausser I, Aufenvenne K, Walker T, et al. Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype. Hum Mol Genet. Nov 1 2006;15(21):3083-97. [Medline].
17. Cather JC, Cohen PR. Ichthyosiform sarcoidosis. J Am Acad Dermatol. May 1999;40(5 Pt 2):862-5. [Medline].
18. Haas AA, Arndt KA. Selected therapeutic applications of topical tretinoin. J Am Acad Dermatol. Oct 1986;15(4 Pt 2):870-7. [Medline].
19. Hofmann B, Stege H, Ruzicka T, Lehmann P. Effect of topical tazarotene in the treatment of congenital ichthyoses. Br J Dermatol. Oct 1999;141(4):642-6. [Medline].
20. Anton-Lamprecht I, Hofbauer M. Ultrastructural distinction of autosomal dominant ichthyosis vulgaris and X-linked recessive ichthyosis. Humangenetik. 1972;15(3):261-4. [Medline].
21. Aram H. Acquired ichthyosis and related conditions. Int J Dermatol. Sep 1984;23(7):458-61. [Medline].
22. Brenner S. Acquired ichthyosis in AIDS. Cutis. May 1987;39(5):421-3. [Medline].
23. Buxman M, Hickman J, Ragsdale W, Stretcher G, Krochmal L, Wehr RF. Therapeutic activity of lactate 12% lotion in the treatment of ichthyosis. Active versus vehicle and active versus a petrolatum cream. J Am Acad Dermatol. Dec 1986;15(6):1253-8. [Medline].
24. Compton JG, DiGiovanna JJ, Johnston KA, Fleckman P, Bale SJ. Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1. Exp Dermatol. Dec 2002;11(6):518-26. [Medline].
25. Cooper MF, Wilson PD, Hartop PJ, Shuster S. Acquired ichthyosis and impaired dermal lipogenesis in Hodgkin's disease. Br J Dermatol. Jun 1980;102(6):689-93. [Medline].
26. Dykes PJ, Marks R. Acquired ichthyosis: multiple causes for an acquired generalized distrubance in desquamation. Br J Dermatol. Sep 1977;97(3):327-34. [Medline].
27. Feinstein A, Ackerman AB, Ziprkowski L. Histology of autosomal dominant ichthyosis vulgaris and X-linked ichthyosis. Arch Dermatol. May 1970;101(5):524-7. [Medline].
28. Fleckman P, Holbrook KA, Dale BA, Sybert VP. Keratinocytes cultured from subjects with ichthyosis vulgaris are phenotypically abnormal. J Invest Dermatol. May 1987;88(5):640-5. [Medline].
29. Goldsmith LA, Baden HP. Management and treatment of ichthyosis. N Engl J Med. Apr 13 1972;286(15):821-3. [Medline].
30. Humbert P, Agache P. Acquired ichthyosis: a new cutaneous marker of autoimmunity. Arch Dermatol. Feb 1991;127(2):263-4. [Medline].
31. Kato N, Yasukawa K, Kimura K, Yoshida K. Anaplastic large-cell lymphoma associated with acquired ichthyosis. J Am Acad Dermatol. May 2000;42(5 Pt 2):914-20. [Medline].
32. Kuokkanen K. Ichthyosis vulgaris. A clinical and histopathological study of patients and their close relatives in the autosomal dominant and sex-linked forms of the disease. Acta Derm Venereol Suppl (Stockh). 1969;62:1-72. [Medline].
33. Liu P, Yang Q, Wang X, Feng A, Yang T, Yang R, et al. Identification of a Genetic Locus for Ichthyosis Vulgaris on Chromosome 10q22.3-q24.2. J Invest Dermatol. Dec 13 2007;[Medline].
34. London RD, Lebwohl M. Acquired ichthyosis and hyperparathyroidism. J Am Acad Dermatol. Oct 1989;21(4 Pt 1):801-2. [Medline].
35. Matarasso SL, Bruce S. Ichthyosiform sarcoidosis: report of a case. Cutis. Jun 1991;47(6):405-8. [Medline].
36. Nirunsuksiri W, Presland RB, Brumbaugh SG, Dale BA, Fleckman P. Decreased profilaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control. J Biol Chem. Jan 13 1995;270(2):871-6. [Medline].
37. Nirunsuksiri W, Zhang SH, Fleckman P. Reduced stability and bi-allelic, coequal expression of profilaggrin mRNA in keratinocytes cultured from subjects with ichthyosis vulgaris. J Invest Dermatol. Jun 1998;110(6):854-61. [Medline].
38. Patel N, Spencer LA, English JC 3rd, Zirwas MJ. Acquired ichthyosis. J Am Acad Dermatol. Oct 2006;55(4):647-56. [Medline].
39. Presland RB, Boggess D, Lewis SP, Hull C, Fleckman P, Sundberg JP. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice: an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris. J Invest Dermatol. Dec 2000;115(6):1072-81. [Medline].
40. Rawlings AV, Scott IR, Harding CR, Bowser PA. Stratum corneum moisturization at the molecular level. J Invest Dermatol. Nov 1994;103(5):731-41. [Medline].
41. Sanli H, Akay BN, Arat M, Koçyigit P, Akan H, Beksac M, et al. Vitiligo after Hematopoietic Cell Transplantation: Six Cases and Review of the Literature. Dermatology. Feb 20 2008;216(4):349-354. [Medline].
42. Schwartz JL, Goldsmith LA. The history of genodermatoses. Clin Dermatol. Jan-Mar 1985;3(1):7-13. [Medline].
43. Schwartz RA, Williams ML. Acquired ichthyosis: a marker for internal disease. Am Fam Physician. Feb 1984;29(2):181-4. [Medline].
44. Scott IR, Harding CR, Barrett JG. Histidine-rich protein of the keratohyalin granules. Source of the free amino acids, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum. Biochim Biophys Acta. Oct 28 1982;719(1):110-7. [Medline].
45. Shwayder T, Ott F. All about ichthyosis. Pediatr Clin North Am. Aug 1991;38(4):835-57. [Medline].
46. Sybert VP, Dale BA, Holbrook KA. Ichthyosis vulgaris: identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules. J Invest Dermatol. Mar 1985;84(3):191-4. [Medline].
47. Thomas JR 3rd, Doyle JA. The therapeutic uses of topical vitamin A acid. J Am Acad Dermatol. May 1981;4(5):505-13. [Medline].
48. Wells RS. Ichthyosis. Br Med J. Dec 17 1966;2(5528):1504-6. [Medline].
49. Wells RS, Kerr CB. Clinical features of autosomal dominant and sex-linked ichthyosis in an English population. Brit Med J. April 1966;1:947-50.
50. Wells RS, Kerr CB. The histology of ichthyosis. J Invest Dermatol. 1966;46:530-5.
51. Zhong W, Cui B, Zhang Y, Jiang H, Wei S, Bu L, et al. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22. J Hum Genet. 2003;48(7):390-2. [Medline].
52. Ziprkowski L, Feinstein A. A survey of ichthyosis vulgaris in Israel. Br J Dermatol. Jan 1972;86(1):1-8. [Medline].

Article Last Updated: May 12, 2008