The Ichthyoses: A Guide to Clinical Diagnosis, Genetic Counseling, and Therapy

256 Pages·1989·10.181 MB·English

by  Priv. Doz. Dr. Heiko Traupe (auth.)

Heiko Traupe
The Ichthyoses
A Guide to Clinical Diagnosis,
Genetic Counseling, and Therapy
Foreword by R. Happle
With a contribution by B. Melnik
With 81 Figures and 35 Tables
Springer-Verlag Berlin Heidelberg New York
London Paris Tokyo Hong Kong
PriV. Doz. Dr. HEIKO TRAUPE
Department of Human Genetics,
University of Nijmegen,
Geert Grooteplein zuid 20,
NL-6500 HB Nijmegen
ISBN 978-3-642-73652-0 ISBN 978-3-642-73650-6 (eBook)
DOI 10.1007/978-3-642-73650-6
Library of Congress Cataloging-in-Publication Data
Traupe, Heiko; The ichthyoses: a guide to diagnosis, genetic counseling, and therapy 1
Heiko Traupe ; foreword by R Happle. p. cm. Includes bibliographies and index.
ISBN -13 :978-3-642-73652-0 (U.S. :alk. paper)1. Ichthyosis. 2.Genetic counseling.1. Title.
[DNLM: I. Genetic Counseling. 2. Ichthyosis-diagnosis.3. Ichthyosis-therapy. WR 500 177 iJ
RLA35.T773 1989 616.5'44-dc20 89-19682 CIP
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Foreword
It is a great pleasure for me to see this work in print. As outlined
by Dr. Traupe, at least 20 different types of ichthyosis have been
identified to date. This book will effectively help to establish a
correct diagnosis, as a basis for genetic counseling. Dr. Traupe
proposes a new classification of the ichthyoses, based on reason
able clinical criteria. He lets the reader share in his enormous
knowledge and safely guides him through the difficult field of
nomenclature. He describes the particular nature of these scaling
disorders in a manner as simple as possible.
During the last few years, research on ichthyosis has become a
fascinating scientific challenge due to the introduction of novel
investigative approaches. The main advantage of this book lies in
the fact that the author successfully combines recent achievements
made in lipid analysis, enzymology, electron microscopy, and
molecular genetics.
Heiko Traupe began his career in dermatology 11 years ago, as a
resident in the Department of Dermatology in Munster. As we
were both interested in the genetic aspects of skin diseases, this
was the starting point of a most fruitful collaboration, which is still
continuing. During our common work in Munster, Dr. Traupe was
able, thanks to his unceasing clinical curiosity, to describe many
novel aspects within the field of ichthyosis, and I took pride in
coauthoring papers on new items such as cryptorchidism as a fea
ture associated with X-linked recessive ichthyosis, autosomal
dominant lamellar ichthyosis, and alopecia ichthyotica.
Both of us were impressed by the fact that even today it is still
possible to detect new clinical entities, simply by use of a pre
pared mind. While rereading the first article we wrote together,
which deals with the ichthyosis vulgaris group (reference 17 on
page 53), I was surprised by the fact that we had already men
tioned ichthyosis bullosa of Siemens then. I still remember the
day, 5 years later, when Dr. Traupe presented to me a family af
fected with an uncommon type of ichthyosis, stating that this was
most probably a skin disease which had been describ'ed 50 years
before by Siemens and which had then fallen into oblivion. Dr.
Traupe had immediately realized that we were dealing with a sec
ond family affected with ichthyosis bullosa of Siemens.
VI Foreword
In this volume the author follows the tradition of the great
morphologists by carefully presenting the historical aspects of
given disease. Yet he is an iconoclast, rejecting time-honored mis
nomers such as "ichthyosiform erythroderma" or redefining the
KID syndrome because he feels that the associated keratinization
disorder is not an ichthyosis at all.
The author clearly distinguishes between confirmed data and
his opinions, which are based, however, on ample clinical experi
ence. The chapter on therapeutic modalities will be especially
useful for any clinician dealing with patients affected with ich
thyosis.
Although I had no part in the preparation of this book, I con
sider it a privilege to have had the opportunity to discuss many
points beforehand with the author and to be the first to congratu
late him on his outstanding work. I look forward to further fruit
ful discussions with him on clinical diagnosis, genetic counseling,
and therapy of the ichthyoses.
I anticipate that this book will be considered a milestone in the
literature on ,keratinization disorders. It will certainly be of great
value to dermatologists, geneticists, and pediatricians and exten
sively used by them for the best of their patients.
Nijmegen, The Netherlands RUDOLF HAPPLE
June 1989
Preface
By convention, those cornification disorders that are genetic in
nature and in which visible scaling involves the entire body sur
face are called "ichthyoses". Though usually not life threatening,
many of these diseases can be very disfiguring and can cause con
siderable distress to their sufferers throughout life.
To many colleagues, the field of the ichthyoses is a perplexing
quagmire. Because of the enormous genetic heterogeneity and be
cause of possible phenotypic variations even within the same ge
netic type, they often feel uneasy when confronted with an indi
vidual patient. I hope that having digested this book, the reader
will tread on solid ground in such situations and will be able to
entertain a definite diagnosis in more than 90% of his or her pa
tients.
To help our patients, the next step should then be to offer ge
netic advice to them and their families. This should be done in
cooperation with a clinical geneticist or a department specialized
in genetic counseling. Throughout the book, special emphasis is
given to this part of patient care, and problems relating to disease
prevention by prenatal diagnosis are discussed in the individual
chapters.
In contrast to many other genetic diseases, treatment is availa
ble for the ichthyoses. Because therapy is symptomatic, we can be
"lumpers" in this respect. Most patients with ichthyosis can be
managed irrespective of their genetic type in more or less the
same ways, though some differences in response to retinoids ex
ist. As the title states, it is the aim of this book to provide a guide
for clinical diagnosis, genetic counseling, and therapy in this het
erogeneous group of diseases.
It is obvious that the process of identifying new entities within
the framework of ichthyosis has not yet been completed. There
are two reasons for this. On the one hand, some of these diseases
are very uncommon. Therefore, distinct, but so far unrecognized
clinical syndromes such as the ichthyosis follicularis, a,trichia, and
photophobia (IFA P) syndrome still emerge. On the other hand,
pedigree analysis and newly gained ultrastructural and biochemi
cal insights result in splitting of long-recognized diseases thought
to represent a single entity, such as lamellar ichthyosis.
VIn Preface
I am sometimes asked by dermatologist colleagues: "Is it at all
important to pin down new types of ichthyoses? Are the four 'ma
jor' types not enough? Why don't you work on a common disease
like atopic dermatitis or psoriasis?" Questions like these reveal a
lack of comprehension as to why research into genetic skin dis
eases is done. Establishing a correct diagnosis is not art for art's
sake; it is the prerequisite for adequate genetic counseling and
thus for adequate patient care. In some diseases like Refsum's
syndrome, missing the proper diagnosis has far-reaching negative
repercussions on the health of these patients. Moreover, before
we can learn more about the biochemistry and molecular genetics
of the ichthyoses it is necessary to establish a diagnosis that is as
precise as possible. To put it in the words of Dr. Mary Williams,
of San Francisco, one has to "sort out apples from oranges."
It was only 20 years ago that Dr. Wells and Dr. Kerr identified
X-linked recessive ichthyosis as a new type of ichthyosis and sep
arated it from the more common autosomal dominant ichthyosis
vulgaris. Without their work, the fascinating recent advances with
regard to steroid sulfatase deficiency would not have been possi
ble. X-linked recessive ichthyosis has become a model disease for
both disciplines, dermatology and genetics. It is now an open
window, allowing deep insights into structure and function of the
skin and regulation of X-linked genes. In the future, the other
types of ichthyosis may likewise contribute to similar advances.
Last but not least, I want to acknowledge the help of many
colleagues and friends in preparing this book. My own involve
ment in ichthyosis research began in 1978. Over many years, Dr.
Rudolf Happle, now of Nijmegen, has been an enthusiastic coun
terpart and mentor. lowe a great deal to him, and I am glad he
accepted the invitation to write the foreword.
I had the pleasure of working for almost 10 years in a depart
ment with a lively scientific and, at the same time, agreeable and
friendly atmosphere. Much of the special spirit of the Munster
Department of Dermatology is due to its head, Dr. Egon Macher.
I want to specifically thank Dr. Gisela Bonsmann, Munster, and
Dr. Henning Hamm, Munster, who helped a great deal with the
clinical studies. Over many years, Dr. C. Muller, now of Wurz
burg, and Dr. H. H. Ropers, now of Nijmegen, performed steroid
sulfatase tests for us. Dr. G. Kolde, Munster, studied the ultra
structure in some of our patients and kindly provided a number
of electron micrographs. My warmest thanks also go to a number
of nonacademic co-workers, especially to the two excellent pho
tographers of the Munster Department of Dermatology, Mr.
P. Wissel and Mrs. Jutta Buckmann. I am deeply indebted as well
to Mrs. M. von Lovenberg, who typed the manuscript.
Dr. Bodo Melnik, Dusseldorf, kindly accepted the task of writ
ing a chapter on epidermal lipid metabolism and its relationship
Preface IX
to the ichthyoses. His important contribution shows how closely
ichthyosis research is now interwoven with basic problems of skin
metabolism and terminal epidermal differentiation. I am in
debted to a great number of colleagues who provided me with
photographic material. These are Dr. Ingrun Anton-Lamprecht
and Dr. Marie-Luise Arnold, both of Heidelberg, Dr. T.Gedde
Dahl, Troms0, Norway, Dr. R. Happle, Nijmegen, Dr. G. Kolde,
Munster, Dr. W. Kuster, Dusseldorf, Dr. F. Lawlor, London, Dr.
B. Mevorah, Lausanne, Dr. H. H0yer, R0nne, Denmark, Dr.
C. R. Muller, Wurzburg, Dr. P. Unamuno, Salamanca, and Dr.
Mary Williams, San Francisco.
I thank Hoffmann-La Roche Company, Federal Republic of
Germany, for a financial contribution to lower the costs of print
ing. I am much indebted to the Deutsche Forschungsgemeinschaft
which fully supports me (grant Tr 228/1-1).
Reactions, comments and suggestions on this book and on the
subject of ichthyosis are most welcome. For correspondence,
please note that I am now affiliated with the Department of Hu
mim Genetics at the University of Nijmegen, The Netherlands.
Nijmegen, The Netherlands HEIKO TRAUPE
June 1989
Table of Contents
1 Introduction 1
1.1 Definition of the Term "Ichthyosis" 3
1.2 History of the Ichthyoses . . . . . . 4
1.3 New Classification and Tables for Differential
Diagnosis of the Ichthyoses 9
1.4 Epidermal Lipids and the Biochemistry of
Keratinization B. MELNIK . . . . . . . . . 15
1.4.1 Introduction ................. 15
1.4.2 Changes in Lipid Composition of Epidermal
Layers during Keratinization . . . . . . . . . . 16
1.4.3 Organization and Metabolism of Epidermal Lipids 21
1.4.4 Epidermal Lipids and the Permeability Barrier 25
1.4.5 Effect of Retinoids on Epidermal Lipid Metabolism 26
1.4.6 Disorders of Cornification Associated with
Abnormalities in Epidermal Lipid Metabolism 27
1.4.7 Conclusion . . . . . . . . . . . . . . . . . . . . . 35
2 Isolated Vulgar Ichthyoses ...... 43
2.1 Autosomal Dominant Ichthyosis Vulgaris 45
2.1.1 Historical Aspects ..... . . . . . . . . . . . . . 45
2.1.2 Incidence and Clinical Features .... 45
2.1.3 Histologic and Ultrastructural Features 49
2.1.4 Biochemical Aspects 49
2.1.5 Genetic Counseling ..... . 52
2.2 X-Linked Recessive Ichthyosis 54
2.2.1 Historical Aspects 54
2.2.2 Incidence ........... . 55
2.2.3 Clinical Features . . . . . . . . 55
2.2.4 Histologic and Ultrastructural Features 62
2.2.5 Biochemistry . . . . . . . . . . . . . . . 64
XII Table of Contents
2.2.6 Genetics 70
2.2.7 Genetic Counseling 73
3 Associated Ichthyoses of the Vulgaris Type ..... 79
3.1 Refsum's Syndrome (Heredopathia Atactica
Polyneuritiformis) · ... 81
3.1.1 Historical Aspects · .... 81
3.1.2 General Clinical Features . 81
3.1.3 Cutaneous Manifestations 82
3.1.4 Histologic and Ultrastructural Findings 84
3.1.5 Biochemical Aspects 85
3.1.6 Therapy ....... 86
3.1.7 Genetic Counseling 86
3.2 Associated Steroid-Sulfatase Deficiency 88
3.2.1 X/Y Translocations and Loss of Xp223-pter 88
3.2.2 XRI and Kallmann's Syndrome ...... 88
3.2.3 XRI and Hypertrophic Pyloric Stenosis:
Possible Implications for the Carter Effect 89
3.2.4 Genetic Counseling ............. 89
3.3 Ichthyosis and Hypogonadism: Reflections on the
so-called Rud's Syndrome 91
3.3.1 General Remarks · .................. 91
3.3.2 How a Syndrome was Made up ........... 91
3.3.3 Current Concepts: Evidence for Genetic Heterogeneity 92
3.4 Multiple Sulfatase Deficiency 98
3.4.1 Historical Aspects · ...... 98
3.4.2 Clinical Features . . . . . . . . 98
3.4.3 Biochemical and Genetic Aspects 99
3.4.4 Genetic Counseling ........ 100
4 Isolated Congenital Ichthyoses 103
4.1 Harlequin Fetus 105
4.1.1 Historical Aspects 105
4.1.2 Clinical Features . 105
4.1.3 Histologic Features 108
4.1.4 Biochemical Aspects 108
4.1.5 Genetic Counseling 108
4.2 The Lamellar Ichthyoses 111
4.2.1 Classification, History, and Remarks on Nomenclature 111