I
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I
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II I
P almoplantar keratoderma with sclerodactyly (Huriez syndrome) Annalisa Patrizi, MD, Vito Di Lernia, MD, and Pasquale Patrone, M D
Bologna, Italy
A syndrome characterized by palmoplantar keratoderma, sclerodactyly, and skin cancer was first described in two families by Huriez et al. The pattern of inheritance was compatible with that of an autosomal dominant disorder. We report a patient with this condition and review the literature. (J AM ACADDERMATOL1992;26:855-7.)
In 1969 Huriez et al. t identified a new syndrome in 42 of 132 members of two families. It was characterized by a diffuse scleroatrophy of the hands, sclerodactyly and keratoderma of the palms, and to a lesser extent, of the soles. Additional features included nail changes and the occurrence of squamous carcinomas in the atrophic skin.t Another familial case has been reported, 2 and the syndrome is classified either as a disorder of the connective tissue or as a keratoderma. 3' 4 We report a patient affected by a condition compatible with the scleroatrophic syndrome described by Huriez. CASE REPORT
A 55-year-old man had an operation for renal stones. During the postoperative period, the patient was referred to us for the evaluation of a sclerodactyly and a palmar keratoderma. The patient reported that keratoderma had developed in childhood and increased in severity without spreading when he began to work as a bricklayer. The sclerodactylyhad also appeared in childhood.The patient reported that his father, who died at 76 years of age of prostatic carcinoma, had a similar condition. His mother, his only sister, and his only son were unaffected. Physical examination showed a diffuse thickening of the palms (Fig. 1), which were yellow in color. In some areas the keratoderma radiated from the palm along the fingers. There was accentuation of the palmar markings but no erythema or scaling. Marked hypohidrosisobliged the patient to wet his hands during work. Sclerodactyly hindered the fingers from being placed flat one against the other (Fig. 2). The skin of the dorsum of both hands appeared slightly thinned. Clubbing was present on the nails
F r o m t h e D e p a r t m e n t of Dermatology, University of Bologna,
Reprint requests: V. Di Lernia, MD, Istituto di Clinica Dermatologica, via Massarenti 1, 40138 Bologna, Italy.
16/4/32017
of both thumbs; the nails of the second, third, and fourth left fingersshowed longitudinal ridging. The keratoderma was not uniform on the soles, but was accentuated over pressure sites. A biopsy specimen from the right palm showed orthokeratotic hyperkeratosis and focal acanthosis and focal papillomatosis without significant alterations in the dermis. The sweat glands appeared normal. Results of routine laboratory studies and radiologic examination of the hands and feet were normal. DISCUSSION The disorder described first by Huriez et al. consists of the following: sclerodactyly, keratoderma of the palms and soles, nail anomalies (aplasia, ridging, and clubbing), and possible malignant degeneration of the affected skin. Hypohidrosis is commonly associated with the disorder. The disease is present at birth or appears in the first years of life. It persists unchanged throughout adult life. The original description of Huriez syndrome included 42 of 132 members in two families from the same geographic areas without common ancestral origin. Malignant cutaneous degeneration was observed in four members in the first family and in two members in the second. Subsequently Lambert et al. z reported a 58-year-old Tunisian man with a similar condition and skin cancer. In his family of five generations and 35 members, there were three affected persons. The inheritance pattern in these three families suggests an autosomal dominant disorder. Because the blood group with phenotype M N S was present in the affected members of the two families reported by Huriez et al.I and in the patient reported by Lambert et al. 2 it has been suggested that the syndrome is inherited together with this blood group. The locus of the gene would be near 855
856
Journal of the American Academy of Dermatology
Patrizi et al.
Fig. 1. Hands showing diffuse thickening of palms without desquamation.
Fig. 2. Evident sclerodactyiy causing contraction of hands. that of the M N S system on the same chromosome. Our patient did not have an M N S phenotype. Sclerodactyly not associated with Raynaud's phenomenon 3 is the most prominent feature of the syndrome; the associated keratoderma is not usually severe. Malignant degeneration is initiated by the
occurrence of skin ulcers on the atrophic skin of the hands. Squamous cell carcinomas often occur as early as the third to fourth decade of life. The differential diagnosis includes disorders characterized by localized sclerosis of the skin of the hands as well as palmoplantar keratodermas. The familial condition described by Huriez et al.1 can be distinguished from scleroderma by its onset at birth, an absence of systemic signs and symptoms, a lack of vasomotor phenomena, and progression during adulthood. A progressive sclerodactyly can occur in patients with diabetes without an associated tylosis. In some severe palmar and plantar keratodermas there is a suggestion of sclerosis, but in the Huriez syndrome the sclerotic changes are disproportionately greater, although the keratoderma is slight and not homogeneous. In patients with prominent keratoderma, Unna-Thost syndrome must be excluded. 1 The latter is commonly associated with hyperhidrosis and only occasionally shows sclerodactyly or nail changes. Malignant degeneration has not been reported.t, s A literature search did not reveal cases other than those published in the French literature, l, 2, 6, 7 This could be ascribed to two factors: first, the rarity of the syndrome, and second, the possibility that some cases may remain undiagnosed because of only minimal sclerodactyly and keratoderma. REFERENCES
I. Huriez C1, Deminati M, Agache P, et al. G~nodermatose scl&o-atrophiante et k6ratodermique des extr6mit&. Ann Dermatol Syphiligr 1969;96:135-46.
Volume 26 Number 5, Part 2 May 1992
2. Lambert D, Planche H, Chapuis JL. La g6nodermatose scl6ro-atrophiante et khratodermique des extrhmit6s. Ann Dermatol V6nhr6ol 1977;104:654-7. 3. Burton JL, Ebling FJG. Disorders of connectivetissue. In: Rook A, Wilkinson DS, Ebling FJG, et al., eds. Textbookof Dermatology. 4th ed. London: Blackwell Scientific, 1986: 1813. 4. Cavalieri R. Disordini ereditari della cheratinizzazione.In: Serri F. Trattato di Dermatologia. Padova: Piecin, 1988: 118. 5. Ebling FJG, Marks R, Rook A. Disordersof keratinization.
Palmoplantar keratoderma with sclerodactyly In: Rook A, Wilkinson DS, Ebling FJG, et al., eds.Textbook of dermatology. 4th ed. London: Blackwelt Scientific 1986: 1453-4. 6. Huriez C1, Agache P, Bombart M, et al. Epitheliomas spinocellulaires sur atrophie cutan6e cong6nitale dans deux families i morbidit~ canc6reuse 61ev6e.Bull Soc Fr Derm Syph 1963;70:24-28. 7. Huriez C1, Agache P, Souillart F, et al. Scl6roatrophie familiale des extr6mitbs avee d6g6n6rescence cellulaires multiples. Butt Soe Fr Dermatol Syph 1963;70:743-4.
Porphyria cutanea tarda in association with human immunodeficiency virus infection in a hemophiliac M a u r e e n G. Conlan, MD, a and W. Keith Hoots, M D a, b Houston, Texas A case of porphyria cutanea tarda in a human immunodeficiency virus-infected patient with hemophilia is reported. Onset of skin manifestations of porphyria cutanea tarda coincided with deterioration of immune function. However, acquired immunedeficiency syndrome has not yet developed with a follow-up interval of 39 months. Treatment with zidovudine and topical steroids has resulted in significant improvement in the skin lesions. The clinical features of 11 other reported cases of human immunodeficiency virus-associated porphyria cutanea tarda are reviewed. The data suggest that a true association exists between human immunodeficiency virus infection and porphyria cutania tarda, with onset of clinical signs of porphyria cutanea tarda coincident with declining immunologic function. (J AM ACAD DERMATOL 1992;26:857-9.) Infection with the h u m a n immunodeficiency virus ( H I V ) has been associated with numerous cutaneous manifestations. Recent reports suggest a possible association between H I V infection and porphyria cutanea t a r d a (PCT). 1-6 Although this may be coincidental, the increasing number of reports suggest that a true association m a y exist. We report the development of P C T in an HIV-infected patient with hemophilia in association with declining immunologic function and improvement after the initiation of zidovudine therapy. CASE R E P O R T A 56-year-old white man had severe hemophilia A (less than 1% factor VIII activity) since childhood. He received Fromthe GulfStates HemophiliaCenter and the Departmentsof InternalMedicinea and Pediatrics,bUniversityofTexasHealthScience Center. Reprint requests:Maureen G. Conlan, MD, Divisionof Hematology/ Oncology, Universityof Texas Medical School,Rm. 5.016, 6431 Fannin St., Houston,TX 77030.
16/4/32644
numerous infusions with factor VIII concentrates during his lifetime, with resultant asymptomatic chronic hepatitis. He has consumed moderate amounts of alcohol (four to six beers daily) and smoked cigarettes for more than 10 years. He also has a history &excessive sun exposure with resultant chronic skin changes. In 1983 the patient was first documented as being positive for antibody to HIV (by enzyme linked immunosorbent assay and confirmed by Western blot). At that time his absolute CD4 + lymphocyte count was 362 • 106/L, and the CD8 + lymphocyte count was 922 • 106/L. In April 1987 he developed blood-filled blisters, milia, and hyperkeratotic plaques on the dorsa of his hands. His face was erythematous and flushed with hypertrichosis around the temples, and his trunk was hyperpigmented. Plasma and urine porphyrin studies were consistent with the diagnosis of PCT. The erythrocyte uroporphyrinogen decarboxylase activity was subsequently measured at 1.1 relative units (normal, 1.0 to 3.0 relative units, Mayo Medical Laboratories, Rochester, Minn.). At that time, his CD4 + count was 176 X 106/L and the CD8 + count was 289 X 106/L. Other blood counts were normal. Hepatitis serology was positive for antibody to hepatitis B surface antigen, core antigen, and e antigen; the
857
I
I
!
II1[
II I
P almoplantar keratoderma with sclerodactyly (Huriez syndrome) Annalisa Patrizi, MD, Vito Di Lernia, MD, and Pasquale Patrone, M D
Bologna, Italy
A syndrome characterized by palmoplantar keratoderma, sclerodactyly, and skin cancer was first described in two families by Huriez et al. The pattern of inheritance was compatible with that of an autosomal dominant disorder. We report a patient with this condition and review the literature. (J AM ACADDERMATOL1992;26:855-7.)
In 1969 Huriez et al. t identified a new syndrome in 42 of 132 members of two families. It was characterized by a diffuse scleroatrophy of the hands, sclerodactyly and keratoderma of the palms, and to a lesser extent, of the soles. Additional features included nail changes and the occurrence of squamous carcinomas in the atrophic skin.t Another familial case has been reported, 2 and the syndrome is classified either as a disorder of the connective tissue or as a keratoderma. 3' 4 We report a patient affected by a condition compatible with the scleroatrophic syndrome described by Huriez. CASE REPORT
A 55-year-old man had an operation for renal stones. During the postoperative period, the patient was referred to us for the evaluation of a sclerodactyly and a palmar keratoderma. The patient reported that keratoderma had developed in childhood and increased in severity without spreading when he began to work as a bricklayer. The sclerodactylyhad also appeared in childhood.The patient reported that his father, who died at 76 years of age of prostatic carcinoma, had a similar condition. His mother, his only sister, and his only son were unaffected. Physical examination showed a diffuse thickening of the palms (Fig. 1), which were yellow in color. In some areas the keratoderma radiated from the palm along the fingers. There was accentuation of the palmar markings but no erythema or scaling. Marked hypohidrosisobliged the patient to wet his hands during work. Sclerodactyly hindered the fingers from being placed flat one against the other (Fig. 2). The skin of the dorsum of both hands appeared slightly thinned. Clubbing was present on the nails
F r o m t h e D e p a r t m e n t of Dermatology, University of Bologna,
Reprint requests: V. Di Lernia, MD, Istituto di Clinica Dermatologica, via Massarenti 1, 40138 Bologna, Italy.
16/4/32017
of both thumbs; the nails of the second, third, and fourth left fingersshowed longitudinal ridging. The keratoderma was not uniform on the soles, but was accentuated over pressure sites. A biopsy specimen from the right palm showed orthokeratotic hyperkeratosis and focal acanthosis and focal papillomatosis without significant alterations in the dermis. The sweat glands appeared normal. Results of routine laboratory studies and radiologic examination of the hands and feet were normal. DISCUSSION The disorder described first by Huriez et al. consists of the following: sclerodactyly, keratoderma of the palms and soles, nail anomalies (aplasia, ridging, and clubbing), and possible malignant degeneration of the affected skin. Hypohidrosis is commonly associated with the disorder. The disease is present at birth or appears in the first years of life. It persists unchanged throughout adult life. The original description of Huriez syndrome included 42 of 132 members in two families from the same geographic areas without common ancestral origin. Malignant cutaneous degeneration was observed in four members in the first family and in two members in the second. Subsequently Lambert et al. z reported a 58-year-old Tunisian man with a similar condition and skin cancer. In his family of five generations and 35 members, there were three affected persons. The inheritance pattern in these three families suggests an autosomal dominant disorder. Because the blood group with phenotype M N S was present in the affected members of the two families reported by Huriez et al.I and in the patient reported by Lambert et al. 2 it has been suggested that the syndrome is inherited together with this blood group. The locus of the gene would be near 855
856
Journal of the American Academy of Dermatology
Patrizi et al.
Fig. 1. Hands showing diffuse thickening of palms without desquamation.
Fig. 2. Evident sclerodactyiy causing contraction of hands. that of the M N S system on the same chromosome. Our patient did not have an M N S phenotype. Sclerodactyly not associated with Raynaud's phenomenon 3 is the most prominent feature of the syndrome; the associated keratoderma is not usually severe. Malignant degeneration is initiated by the
occurrence of skin ulcers on the atrophic skin of the hands. Squamous cell carcinomas often occur as early as the third to fourth decade of life. The differential diagnosis includes disorders characterized by localized sclerosis of the skin of the hands as well as palmoplantar keratodermas. The familial condition described by Huriez et al.1 can be distinguished from scleroderma by its onset at birth, an absence of systemic signs and symptoms, a lack of vasomotor phenomena, and progression during adulthood. A progressive sclerodactyly can occur in patients with diabetes without an associated tylosis. In some severe palmar and plantar keratodermas there is a suggestion of sclerosis, but in the Huriez syndrome the sclerotic changes are disproportionately greater, although the keratoderma is slight and not homogeneous. In patients with prominent keratoderma, Unna-Thost syndrome must be excluded. 1 The latter is commonly associated with hyperhidrosis and only occasionally shows sclerodactyly or nail changes. Malignant degeneration has not been reported.t, s A literature search did not reveal cases other than those published in the French literature, l, 2, 6, 7 This could be ascribed to two factors: first, the rarity of the syndrome, and second, the possibility that some cases may remain undiagnosed because of only minimal sclerodactyly and keratoderma. REFERENCES
I. Huriez C1, Deminati M, Agache P, et al. G~nodermatose scl&o-atrophiante et k6ratodermique des extr6mit&. Ann Dermatol Syphiligr 1969;96:135-46.
Volume 26 Number 5, Part 2 May 1992
2. Lambert D, Planche H, Chapuis JL. La g6nodermatose scl6ro-atrophiante et khratodermique des extrhmit6s. Ann Dermatol V6nhr6ol 1977;104:654-7. 3. Burton JL, Ebling FJG. Disorders of connectivetissue. In: Rook A, Wilkinson DS, Ebling FJG, et al., eds. Textbookof Dermatology. 4th ed. London: Blackwell Scientific, 1986: 1813. 4. Cavalieri R. Disordini ereditari della cheratinizzazione.In: Serri F. Trattato di Dermatologia. Padova: Piecin, 1988: 118. 5. Ebling FJG, Marks R, Rook A. Disordersof keratinization.
Palmoplantar keratoderma with sclerodactyly In: Rook A, Wilkinson DS, Ebling FJG, et al., eds.Textbook of dermatology. 4th ed. London: Blackwelt Scientific 1986: 1453-4. 6. Huriez C1, Agache P, Bombart M, et al. Epitheliomas spinocellulaires sur atrophie cutan6e cong6nitale dans deux families i morbidit~ canc6reuse 61ev6e.Bull Soc Fr Derm Syph 1963;70:24-28. 7. Huriez C1, Agache P, Souillart F, et al. Scl6roatrophie familiale des extr6mitbs avee d6g6n6rescence cellulaires multiples. Butt Soe Fr Dermatol Syph 1963;70:743-4.
Porphyria cutanea tarda in association with human immunodeficiency virus infection in a hemophiliac M a u r e e n G. Conlan, MD, a and W. Keith Hoots, M D a, b Houston, Texas A case of porphyria cutanea tarda in a human immunodeficiency virus-infected patient with hemophilia is reported. Onset of skin manifestations of porphyria cutanea tarda coincided with deterioration of immune function. However, acquired immunedeficiency syndrome has not yet developed with a follow-up interval of 39 months. Treatment with zidovudine and topical steroids has resulted in significant improvement in the skin lesions. The clinical features of 11 other reported cases of human immunodeficiency virus-associated porphyria cutanea tarda are reviewed. The data suggest that a true association exists between human immunodeficiency virus infection and porphyria cutania tarda, with onset of clinical signs of porphyria cutanea tarda coincident with declining immunologic function. (J AM ACAD DERMATOL 1992;26:857-9.) Infection with the h u m a n immunodeficiency virus ( H I V ) has been associated with numerous cutaneous manifestations. Recent reports suggest a possible association between H I V infection and porphyria cutanea t a r d a (PCT). 1-6 Although this may be coincidental, the increasing number of reports suggest that a true association m a y exist. We report the development of P C T in an HIV-infected patient with hemophilia in association with declining immunologic function and improvement after the initiation of zidovudine therapy. CASE R E P O R T A 56-year-old white man had severe hemophilia A (less than 1% factor VIII activity) since childhood. He received Fromthe GulfStates HemophiliaCenter and the Departmentsof InternalMedicinea and Pediatrics,bUniversityofTexasHealthScience Center. Reprint requests:Maureen G. Conlan, MD, Divisionof Hematology/ Oncology, Universityof Texas Medical School,Rm. 5.016, 6431 Fannin St., Houston,TX 77030.
16/4/32644
numerous infusions with factor VIII concentrates during his lifetime, with resultant asymptomatic chronic hepatitis. He has consumed moderate amounts of alcohol (four to six beers daily) and smoked cigarettes for more than 10 years. He also has a history &excessive sun exposure with resultant chronic skin changes. In 1983 the patient was first documented as being positive for antibody to HIV (by enzyme linked immunosorbent assay and confirmed by Western blot). At that time his absolute CD4 + lymphocyte count was 362 • 106/L, and the CD8 + lymphocyte count was 922 • 106/L. In April 1987 he developed blood-filled blisters, milia, and hyperkeratotic plaques on the dorsa of his hands. His face was erythematous and flushed with hypertrichosis around the temples, and his trunk was hyperpigmented. Plasma and urine porphyrin studies were consistent with the diagnosis of PCT. The erythrocyte uroporphyrinogen decarboxylase activity was subsequently measured at 1.1 relative units (normal, 1.0 to 3.0 relative units, Mayo Medical Laboratories, Rochester, Minn.). At that time, his CD4 + count was 176 X 106/L and the CD8 + count was 289 X 106/L. Other blood counts were normal. Hepatitis serology was positive for antibody to hepatitis B surface antigen, core antigen, and e antigen; the
857
