Editorial Dermatology 1992:185:163-165
D epartm ent of Dermatology, University of Basel. Switzerland
Classification of Autosomal Dominant Palmoplantar Keratoderma: Past - Present - Future
The keratodermas inherited in an autosomal domi nant way are a heterogeneous group of disorders character ized by thickening of the palms and soles due to abnormal kcratinization. A unifying concept to classify these disor ders of cornification is not yet available. The individual entities arc based on clinical descriptions and morphology of the lesion, modes of inheritance, histological findings and biochemical defects. As long as the genetic defects remain unknown, confusion in the classification of palmo plantar keratoderma (PPK) will persist. In this issue Bcylot-Barry et al. [ 1] report on an autoso mal dominant palmoplantar inflammatory keratoderma consistent with a clinical variant of Greither’s disease. The authors discuss the relation of Grcither's disease. UnnaThost's keratoderma and the epidermolytic type of Vomer. These entities were characterized by their histological and clinical differences. The Vomer type is known to have epi dermolytic hyperkeratosis [2], Hamm et al. [3] concluded from their retrospective study that epidermolytic PPK of Vomer represents the most frequent form, and they doubt ed the existence of Unna-Thost-typc PPK. The identity of PPK of the Unna-Thost type with the Vorner type has recently been shown [4|; these authors reexamined a patient of Thost’s original family; histology revealed an epi dermolytic pattern. In addition Kansky and Arzcnsek [5] questioned, whether Greither’s disease is a separate noso logic entity or just a variant of Unna-Thost’s type. The results from Hamm et al. [3] seem to support this view. In the ninth edition of McKusick’s catalogs of inherited dis eases, the number 148400 unifies keratosis palmaris et plantaris familiaris (tylosis, keratosis of Greithcr, hcreditarv palmoplantar keratoderma and Unna-Thost disease)
H
How should we systematically classify the autosomal dominant PPK in a practical way? Table 1 may give a sim ple decision analysis for the classification of PPK. Table 2 lists some of the entities of PKK inherited in an autosomal dominant pattern. According to Franceschetti and Schnydcr 171the mode of inheritance is an important pile of diag nosis. They separate autosomal dominant from autosomal recessive and sex-linked traits. Furthermore they distinguish isolated forms (keratosis diffusa circumscripta, keratosis palmoplantaris striata or linearis, keratosis palmoplantaris papulosa or maculosa, keratosis extremitatum progrediens Greithcr and keratosis palmoplantaris mutilans) from varie ties with associated symptoms (variants from ectodermal dysplasia including Naegeli-Franceschetti-Jadassohn syn drome. keratoderma with ocular abnormalities, some with lipomas and osteopoikilosis). In addition autosomal domi nant PPK associated with squamous cell carcinoma of the skin and esophageal cancer [8], with clinodactyly [9]. with neurological signs 110], sensorineural deafness [11], gingival hyperkeratosis [ 12] and acrocyanosis [13] exist. As a rule his tology is not very helpful. A further possibility is to distin guish the morphological presentation of keratoderma. Some authors encourage to separate diffuse PPK from focal manifestations. A diffuse, punctate or striate pattern exists with autosomal dominant inheritance [ 14].Thisdistinction is often very useful, although the clinical spectrum of PPK may be variable. My colleagues and I have recently reexamined the original family with Naegeli-Franceschetti-Jadassohn syndrome, reported to have a diffuse pattern of PPK. Some of the patients presented with diffuse, some with punctate, some with punctate keratosis of the palmar creases and oth ers with a linear pattern [13], Morphology seems not to be as reliable as the genetic pattern. The definite diagnosis will be
Peter It. Itin. MO Department of Dermatology University of Basel Petersgrahen 4. CM—1031 Basel (Switzerland)
Downloaded by: Kings's College London 137.73.144.138 - 10/29/2017 2:26:36 PM
P.H. Itin
determination of the genetic defect and its chromosomal localization. Now what about Grcither’s disease? This autosomal dominant inherited PPK has a distinct clinical presentation. According to the original description by Grcithcr [16] and later by Salamon [17, 18] the disease starts after the second year of life which is later than in Unna-Thost disease. Kera toses of palms and soles arc often very slight or even absent, but transgression on the dorsal aspects of hands and feet is obligatory. Accentuation of the Achilles tendon is typical. Livid erythema and hyperhidrosis arc further fea tures. Often erythematous keratosis exists on the elbows and knees. Although the name keratosis extremitatum hereditaria progrediens was created by Grcithcr, involution after 60 years is often present. Several case reports on Greithcr’s syndrome appeared in the literature which differed from the original cases [19-21]. In some of these patients keratoderma started much earlier than in the original cases. This was also the case in the patient of Beylot-Barry ct al. [1]. Simultaneous occurrence of erythrokeratodermia variabilis with Greither's disease has been reported [22], No specific histology exists, and ultrastructural examinations have not been performed extensively until today [23]. This fact makes the contribution of BeylotBarry et al. [1] very important, who present increased des mosomes and abnormal cell-to-ccll junctions as well as aberration of the cytoskclcton with filament aggregation. In our own case similar findings were obtained by transmis sion electron microscopy. Further ultrastructural research and analysis of the keratins and markers of differentiation may shed more light on the understanding of Greither's dis ease and will probably help to classify more exactly the group of autosomal dominant inherited PPK [24].
Table 1. Scheme for classification o f PPK Genetics
Morphology
Distribution
autosomal dominant autosomal recessive sex-linked diffuse focal linear isolated lesions associated symptoms
Table 2. Classification o f autosomal dominant PPK Diffuse, autosomal dominant PPK without associated disease Unna-Thost and V örner types. G reither's disease Vohwinkcl's type Focal, autosomal dominant PPK without associated disease Keratosis palmoplantaris papulosa/maculosa/nummulans Keratosis palm oplantaris striata Porokeratosis punctata palmaris et plantaris Porokeratosis plantaris et palmaris et disseminata A crokcratoclastoidosis PPK with associated disease Ectoderm al dysplasias including Nacgcli-Franccschett¡-Jadassohn syndrome and pachyonychia congenita PPK with malignancy PPK with clinodactyly PPK with spastic paralysis PPK with gingival hyperkeratosis
References
I(>4
4 Küster W. Becker A: Indication for the iden tity of palmoplantar keratoderma type UnnaThost with type Vörner. Thost's family revis ited 110 years later. Acta Derm Vcncrcol (Slockh) 1992:72:120-122. 5 Kansky A. Arzensck J: Is palmoplantar kera toderma of Greither's type a separate nosolog ic entity? Dermatológica 1979:158:244-248. 6 McKusick VA: Mcndclian Inheritance in Man: Catalogs of Autosomal Dominant. Autosomal Recessive, and X-Linkcd Phenotypes, ed 9. Baltimore. Johns Hopkins University Press. 1990. p 550. 7 Franceschelti A. Sehnyder LAV: Versuch einer klinisch-genetischen Klassifikation der heredi tären Palmoplantarkeratosen unter Berück sichtigung assoziierter Symptome. Dermatoló gica 1960:120:154-178.
Itin
8 Yesudian P. Premalatha S. Thamhiah AS: Genetic tylosis with malignancy: A study of a South Indian pedigree. Br J Dermatol 1980; 102:597-600. 9 Aguirre-Negrele MG. Hernandez A. Ramircz-Soltcro S. Gonzalez-Mendoza A. Nazara Z. Vaca G. Cantu JM: Keratosis palmaris et plantaris with clinodactyly: A distinct autoso mal dominant genodermatosis. Dermatológica 19S 1:162:300-303. 10 Powell FC. Veneneie PY. Gordon II. Winkelmann RK: Keratoderma and spastic paralysis. Br J Dermatol 1983:109:589-596. 11 Shariand M. Bleach NR. Goberdhan PD. Pat ton MA: Autosomal dominant palmoplantar hyperkeratosis and sensorineural deafness in three generations. .1 Med Genet 1992:29: 50-52.
Classification of Autosomal Dominant PPK
Downloaded by: Kings's College London 137.73.144.138 - 10/29/2017 2:26:36 PM
1 Beylot-Barry M. Tai'eb A. Surlcvc-Bazcillc JF.. Maleville J: Inflammatory familial palmoplantar keratoderma: Greither's disease? Derma tology I992:185:210-214. 2 Requena I.. Schoendorff C. Sanchez Yus F: Hereditary cpidcrmolytic palmo-plantar kera toderma (Vörner type) - Report of a family and review of the literature. Clin Exp Derma tol 1991:16:383-388. 3 Hamm II. 11apple R. ButterfassT. Traupe H: Epidcrmolytic palmoplantar keratoderma of Vörner: Is it the most frequent type of heredi tary palmoplantar keratoderma? Dermatoló gica 1988:177:138-145.
17 Salamon T: Über einige Fälle von Keratosis extremitatum hereditaria progrediens mit dominantem Erbgang (Grcithcr). Z Hautkr 1960:29:289 298. 18 Salamon T: Klinische Variationen innerhalb einiger Entitäten der sogenannten erblichen Palmoplantarkeratosen. Zugleich ein Beitrag zu deren Phänogenese. Dermatol Monatssehr 1991:177:483-492. 19 Berg H: Keratoma palmare et plantare trans gredíais (Grcithcr). Z Hautkr 1966:41: 207-208. 20 Hübner U. Rönisch P: Keratosis palmoplanta ris progrediens et transgredíais und heterozy gote Bcla-Thalassämie. Dermatol Wochcnschr 1980:166:187. 21 Rook AJ: Progressive palmo-plantar keratoderma - Grcithcr's syndrome. Br J Dermatol 1967:79:302.
22 Wollina U. Knopf B. Schaaschmidt H. Frille I: Familiäre Koexistenz von Erythrokeratodcrmia variabilis und Keratosis palmoplantaris transgrediens et progrediens. Hautarzt 1989: 40:169-172. 23 Syberi VP. Dale BA. Holbrook KA: Palmarplantar keratoderma. A clinical, ultrastruc tural. and biochemical study. .1 Am Acad Dermatol 1988:18:75-86. 24 Fartasch M. Vigneswaran N. Diepgen TE. Hornstein OP: Abnormalities of kératinocyte maturation and differentiation in keratosis pal moplantaris striata. Immunohistochemical and ultrastructural study before and during etreti nate therapy. Am J Dcrmatopathol 1990:12: 275-282.
165
Downloaded by: Kings's College London 137.73.144.138 - 10/29/2017 2:26:36 PM
12 Young WG. Newcomb GM. Daley TJ: Focal palmoplantar and gingival hyperkeratosis syn drome: Report of a family, with cytologic, ultrastructural, and histochcmical findings. Oral Surg Oral Med Oral Pathol 1982:53: 473 4S2. 13 Nielsen PG: Diffuse palmoplantar keratoderma associated with acrocyanosis. A family study. Acta Derm Vcncrcol (Stockh) 1989:69: 156-161. 14 Grcithcr A: Erbliche Palmoplantarkeratosen. Hautarzt 1977:28:395-403. 15 hin PU. Lautcnschlagcr St. Meyer R. Mcvorah B. Rufli T: Natural history of the NacgeliFranceschetti-Jadassohn syndrome and further delineation of the symptom complex. .1 Am Acad Dermatol, in press. 16 Grcithcr A: Keratosis extremitatum heredita ria progrediens mit dominantem Erbgang. Hautarzt 1952:3:198-203.
D epartm ent of Dermatology, University of Basel. Switzerland
Classification of Autosomal Dominant Palmoplantar Keratoderma: Past - Present - Future
The keratodermas inherited in an autosomal domi nant way are a heterogeneous group of disorders character ized by thickening of the palms and soles due to abnormal kcratinization. A unifying concept to classify these disor ders of cornification is not yet available. The individual entities arc based on clinical descriptions and morphology of the lesion, modes of inheritance, histological findings and biochemical defects. As long as the genetic defects remain unknown, confusion in the classification of palmo plantar keratoderma (PPK) will persist. In this issue Bcylot-Barry et al. [ 1] report on an autoso mal dominant palmoplantar inflammatory keratoderma consistent with a clinical variant of Greither’s disease. The authors discuss the relation of Grcither's disease. UnnaThost's keratoderma and the epidermolytic type of Vomer. These entities were characterized by their histological and clinical differences. The Vomer type is known to have epi dermolytic hyperkeratosis [2], Hamm et al. [3] concluded from their retrospective study that epidermolytic PPK of Vomer represents the most frequent form, and they doubt ed the existence of Unna-Thost-typc PPK. The identity of PPK of the Unna-Thost type with the Vorner type has recently been shown [4|; these authors reexamined a patient of Thost’s original family; histology revealed an epi dermolytic pattern. In addition Kansky and Arzcnsek [5] questioned, whether Greither’s disease is a separate noso logic entity or just a variant of Unna-Thost’s type. The results from Hamm et al. [3] seem to support this view. In the ninth edition of McKusick’s catalogs of inherited dis eases, the number 148400 unifies keratosis palmaris et plantaris familiaris (tylosis, keratosis of Greithcr, hcreditarv palmoplantar keratoderma and Unna-Thost disease)
H
How should we systematically classify the autosomal dominant PPK in a practical way? Table 1 may give a sim ple decision analysis for the classification of PPK. Table 2 lists some of the entities of PKK inherited in an autosomal dominant pattern. According to Franceschetti and Schnydcr 171the mode of inheritance is an important pile of diag nosis. They separate autosomal dominant from autosomal recessive and sex-linked traits. Furthermore they distinguish isolated forms (keratosis diffusa circumscripta, keratosis palmoplantaris striata or linearis, keratosis palmoplantaris papulosa or maculosa, keratosis extremitatum progrediens Greithcr and keratosis palmoplantaris mutilans) from varie ties with associated symptoms (variants from ectodermal dysplasia including Naegeli-Franceschetti-Jadassohn syn drome. keratoderma with ocular abnormalities, some with lipomas and osteopoikilosis). In addition autosomal domi nant PPK associated with squamous cell carcinoma of the skin and esophageal cancer [8], with clinodactyly [9]. with neurological signs 110], sensorineural deafness [11], gingival hyperkeratosis [ 12] and acrocyanosis [13] exist. As a rule his tology is not very helpful. A further possibility is to distin guish the morphological presentation of keratoderma. Some authors encourage to separate diffuse PPK from focal manifestations. A diffuse, punctate or striate pattern exists with autosomal dominant inheritance [ 14].Thisdistinction is often very useful, although the clinical spectrum of PPK may be variable. My colleagues and I have recently reexamined the original family with Naegeli-Franceschetti-Jadassohn syndrome, reported to have a diffuse pattern of PPK. Some of the patients presented with diffuse, some with punctate, some with punctate keratosis of the palmar creases and oth ers with a linear pattern [13], Morphology seems not to be as reliable as the genetic pattern. The definite diagnosis will be
Peter It. Itin. MO Department of Dermatology University of Basel Petersgrahen 4. CM—1031 Basel (Switzerland)
Downloaded by: Kings's College London 137.73.144.138 - 10/29/2017 2:26:36 PM
P.H. Itin
determination of the genetic defect and its chromosomal localization. Now what about Grcither’s disease? This autosomal dominant inherited PPK has a distinct clinical presentation. According to the original description by Grcithcr [16] and later by Salamon [17, 18] the disease starts after the second year of life which is later than in Unna-Thost disease. Kera toses of palms and soles arc often very slight or even absent, but transgression on the dorsal aspects of hands and feet is obligatory. Accentuation of the Achilles tendon is typical. Livid erythema and hyperhidrosis arc further fea tures. Often erythematous keratosis exists on the elbows and knees. Although the name keratosis extremitatum hereditaria progrediens was created by Grcithcr, involution after 60 years is often present. Several case reports on Greithcr’s syndrome appeared in the literature which differed from the original cases [19-21]. In some of these patients keratoderma started much earlier than in the original cases. This was also the case in the patient of Beylot-Barry ct al. [1]. Simultaneous occurrence of erythrokeratodermia variabilis with Greither's disease has been reported [22], No specific histology exists, and ultrastructural examinations have not been performed extensively until today [23]. This fact makes the contribution of BeylotBarry et al. [1] very important, who present increased des mosomes and abnormal cell-to-ccll junctions as well as aberration of the cytoskclcton with filament aggregation. In our own case similar findings were obtained by transmis sion electron microscopy. Further ultrastructural research and analysis of the keratins and markers of differentiation may shed more light on the understanding of Greither's dis ease and will probably help to classify more exactly the group of autosomal dominant inherited PPK [24].
Table 1. Scheme for classification o f PPK Genetics
Morphology
Distribution
autosomal dominant autosomal recessive sex-linked diffuse focal linear isolated lesions associated symptoms
Table 2. Classification o f autosomal dominant PPK Diffuse, autosomal dominant PPK without associated disease Unna-Thost and V örner types. G reither's disease Vohwinkcl's type Focal, autosomal dominant PPK without associated disease Keratosis palmoplantaris papulosa/maculosa/nummulans Keratosis palm oplantaris striata Porokeratosis punctata palmaris et plantaris Porokeratosis plantaris et palmaris et disseminata A crokcratoclastoidosis PPK with associated disease Ectoderm al dysplasias including Nacgcli-Franccschett¡-Jadassohn syndrome and pachyonychia congenita PPK with malignancy PPK with clinodactyly PPK with spastic paralysis PPK with gingival hyperkeratosis
References
I(>4
4 Küster W. Becker A: Indication for the iden tity of palmoplantar keratoderma type UnnaThost with type Vörner. Thost's family revis ited 110 years later. Acta Derm Vcncrcol (Slockh) 1992:72:120-122. 5 Kansky A. Arzensck J: Is palmoplantar kera toderma of Greither's type a separate nosolog ic entity? Dermatológica 1979:158:244-248. 6 McKusick VA: Mcndclian Inheritance in Man: Catalogs of Autosomal Dominant. Autosomal Recessive, and X-Linkcd Phenotypes, ed 9. Baltimore. Johns Hopkins University Press. 1990. p 550. 7 Franceschelti A. Sehnyder LAV: Versuch einer klinisch-genetischen Klassifikation der heredi tären Palmoplantarkeratosen unter Berück sichtigung assoziierter Symptome. Dermatoló gica 1960:120:154-178.
Itin
8 Yesudian P. Premalatha S. Thamhiah AS: Genetic tylosis with malignancy: A study of a South Indian pedigree. Br J Dermatol 1980; 102:597-600. 9 Aguirre-Negrele MG. Hernandez A. Ramircz-Soltcro S. Gonzalez-Mendoza A. Nazara Z. Vaca G. Cantu JM: Keratosis palmaris et plantaris with clinodactyly: A distinct autoso mal dominant genodermatosis. Dermatológica 19S 1:162:300-303. 10 Powell FC. Veneneie PY. Gordon II. Winkelmann RK: Keratoderma and spastic paralysis. Br J Dermatol 1983:109:589-596. 11 Shariand M. Bleach NR. Goberdhan PD. Pat ton MA: Autosomal dominant palmoplantar hyperkeratosis and sensorineural deafness in three generations. .1 Med Genet 1992:29: 50-52.
Classification of Autosomal Dominant PPK
Downloaded by: Kings's College London 137.73.144.138 - 10/29/2017 2:26:36 PM
1 Beylot-Barry M. Tai'eb A. Surlcvc-Bazcillc JF.. Maleville J: Inflammatory familial palmoplantar keratoderma: Greither's disease? Derma tology I992:185:210-214. 2 Requena I.. Schoendorff C. Sanchez Yus F: Hereditary cpidcrmolytic palmo-plantar kera toderma (Vörner type) - Report of a family and review of the literature. Clin Exp Derma tol 1991:16:383-388. 3 Hamm II. 11apple R. ButterfassT. Traupe H: Epidcrmolytic palmoplantar keratoderma of Vörner: Is it the most frequent type of heredi tary palmoplantar keratoderma? Dermatoló gica 1988:177:138-145.
17 Salamon T: Über einige Fälle von Keratosis extremitatum hereditaria progrediens mit dominantem Erbgang (Grcithcr). Z Hautkr 1960:29:289 298. 18 Salamon T: Klinische Variationen innerhalb einiger Entitäten der sogenannten erblichen Palmoplantarkeratosen. Zugleich ein Beitrag zu deren Phänogenese. Dermatol Monatssehr 1991:177:483-492. 19 Berg H: Keratoma palmare et plantare trans gredíais (Grcithcr). Z Hautkr 1966:41: 207-208. 20 Hübner U. Rönisch P: Keratosis palmoplanta ris progrediens et transgredíais und heterozy gote Bcla-Thalassämie. Dermatol Wochcnschr 1980:166:187. 21 Rook AJ: Progressive palmo-plantar keratoderma - Grcithcr's syndrome. Br J Dermatol 1967:79:302.
22 Wollina U. Knopf B. Schaaschmidt H. Frille I: Familiäre Koexistenz von Erythrokeratodcrmia variabilis und Keratosis palmoplantaris transgrediens et progrediens. Hautarzt 1989: 40:169-172. 23 Syberi VP. Dale BA. Holbrook KA: Palmarplantar keratoderma. A clinical, ultrastruc tural. and biochemical study. .1 Am Acad Dermatol 1988:18:75-86. 24 Fartasch M. Vigneswaran N. Diepgen TE. Hornstein OP: Abnormalities of kératinocyte maturation and differentiation in keratosis pal moplantaris striata. Immunohistochemical and ultrastructural study before and during etreti nate therapy. Am J Dcrmatopathol 1990:12: 275-282.
165
Downloaded by: Kings's College London 137.73.144.138 - 10/29/2017 2:26:36 PM
12 Young WG. Newcomb GM. Daley TJ: Focal palmoplantar and gingival hyperkeratosis syn drome: Report of a family, with cytologic, ultrastructural, and histochcmical findings. Oral Surg Oral Med Oral Pathol 1982:53: 473 4S2. 13 Nielsen PG: Diffuse palmoplantar keratoderma associated with acrocyanosis. A family study. Acta Derm Vcncrcol (Stockh) 1989:69: 156-161. 14 Grcithcr A: Erbliche Palmoplantarkeratosen. Hautarzt 1977:28:395-403. 15 hin PU. Lautcnschlagcr St. Meyer R. Mcvorah B. Rufli T: Natural history of the NacgeliFranceschetti-Jadassohn syndrome and further delineation of the symptom complex. .1 Am Acad Dermatol, in press. 16 Grcithcr A: Keratosis extremitatum heredita ria progrediens mit dominantem Erbgang. Hautarzt 1952:3:198-203.
