Buschke-Ollendorff syndrome - differential diagnosis of disseminated connective tissue lesions

ARTICLE

The Buschke-Ollendorff syndrome is an autosomal dominantly inherited syndrome of variable expression characterized by association of disseminated connective tissue nevi and osteopoikilosis [1, 2]. The two symptoms may arise at different ages, therefore the diagnosis and differentiation from papular acne scars, fibroelastolytic papulosis of the neck, papular elastorrhexis and inherited syndromes with connective tissue disorders, i.e. pseudoxanthoma elasticum, juvenile hyaline fibromatosis or familiar cutaneous collagenoma may be difficult in early ages. Careful differential diagnosis is essential for assessing the individual prognosis and for providing genetic counseling. Here, we report a 5 year old boy showing connective tissue nevi of the elastic type together with osteopoikilosis as typical clinical features of the Buschke-Ollendorff syndrome seen at early stage of development.

Case report

A 5-year-old boy was presented, showing multiple skin-colored to yellowish plaques developing for 3 years on the upper part of his left thigh and his lower trunk (Fig. 1). The diameter of the lesions varied from lentil-sized up to a maximum of 2 cm, partly appearing in an aggregated pattern. The boy showed normal physical development, with neither intellectual deficiencies nor evidence for orthopedic, internal or ophthalmological problems. The skin lesions were indolent without functional limitation.

X-ray examination of the right hand revealed discrete spherical condensations in the metacarpal and phalangeal bones (Fig. 2). Similarly, discrete osteopoikilotic condensations were noted on the right foot. No anomalies were found in the chest and pelvis, especially no evidence of supernumerary vertebrae and ribs.

Examination of four other family members revealed a few lentil-sized skin-colored papules on the upper part of the left thigh of his 2-year-old brother and his father.

Histological examination of two lentil-sized papules located on the right thigh of the patient revealed orthohyperkeratosis and papillomatous vaulted epidermis. Dermal elastic fibers were increased in number and size, showing hypertrophy, but there was no fragmentation characteristic of elastic type connective tissue nevi (Fig. 3). Accordingly, no alteration in collagen architecture was found in hematoxylin and eosin stained specimens.

Electron microscopy revealed both collagen fibers with normal appearance as well as areas with marked homogenization. Altered electrolucent elastic fibers and decrease in microfibrillar components occurred (Fig. 4). In some areas thin granular material was detectable. No fragmentation of elastic fibers and no calcification could be detected. These ultrastructural findings were in accordance with the diagnosis of a connective tissue nevus of the elastic type.

Discussion

The association of disseminated connective tissue nevi and osteopoikilosis was first described by Buschke and Ollendorff in 1928 and is now known as Buschke-Ollendorff syndrome [1]. Disseminated elastic type nevi, called juvenile elastoma, as well as disseminated collagen type nevi, called dermatofibrosis lenticularis disseminata, may occur in this syndrome [2-5]. Patients present with disseminated lesions on the trunk, upper arms and upper thighs developing during the first decades of life. Progression after adolescence is rare [6-8].

Osteopoikilotic lesions are usually found incidentally. They are characterized by grain- to pea-sized spherical condensations or fascicular streaks in the skeletal structure of epiphyses and metaphyses of the long bones, pelvis and the bones of hands and feet [9-13]. They develop slowly and are often not detected before late adolescence or later. They represent structural anomalies without functional limitations and may also occur without associated skin lesions [12]. In the case presented here, the exceptional early onset of the skeletal lesions led us to the diagnosis of a Buschke-Ollendorff syndrome at the early age of five years. The occurrence of skin manifestations in the father and the younger brother is in accordance with the autosomal dominant pattern of inheritance of the Buschke-Ollendorff syndrome.

The underlying defect in Buschke-Ollendorff syndrome remains unclear. Defective extracellular matrix is certainly involved. Increased TGF-beta expression with increased elastin production and the role of focal elastin alteration have been discussed controversially [14-16]. However, unrelated but closely located genes may cause this special association between cutaneous and osteopoikilotic lesions. Internal symptoms associated to Buschke-Ollendorff syndrome have been suggested in various case reports, but there is no clear evidence for a significantly increased incidence of any of these diseases [2, 3, 7, 17, 18]. Also, no increase of morbidity or mortality has been reported in the literature.

In our patient no anomalies in skeletal structure, cataracts, peptic ulcer disease or affections of any other additional organ system could be detected. As progression of the nevi, osteopoikilosis and any possibly associated symptoms is unclear during childhood, close clinical follow up is indicated. As the lesions remain asymptomatic and rarely cause cosmetic problems, treatment is seemingly unnecessary. The patient should be informed about the autosomal dominant pattern of inheritance.

In patients presenting connective tissue lesions careful consideration of differential diagnosis is required in order to exclude syndromes associated with internal affections and, sometimes, with poor prognosis.

Collagen and elastic type nevi represent the most frequently observed connective tissue nevi (table I), whereas, glycosaminoglycan nevi and nevi of adventitial connective tissue are less frequent. They occur as solitary or disseminated nevi. In particular, the diagnosis of disseminated connective tissue nevi should be followed by histological characterization and a subsequent search for associated symptoms. They may resemble papular acne scars, a common cutaneous finding, or fibroelastolytic papulosis of the neck which is characterized by papular eruptions on the upper trunk [19, 20].

Papular elastorrhexis is characterized by nonfollicular white papules, decreased elastic tissue and the absence of osteopoikilosis. It may represent an abortive form of Buschke-Ollendorff syndrome and therefore represents an important differential diagnosis [21]. Further, disseminated connective tissue lesions frequently represent the leading symptom of Pseudoxanthoma elasticum, juvenile hyaline fibromatosis, lipoidproteinosis, papular mucinosis and familial cutaneous collagenoma, rare inherited syndromes with various systemic manifestations often associated with increased morbidity and poor prognosis [22-27]. Careful evaluation of the skin lesions, histology, associated features and pattern of inheritance is required for appropriate treatment and genetic counseling (table II). Pseudoxanthoma elasticum-like lesions are also observed in cases of late onset focal dermal elastosis, which, however, affects elderly patients [28].

In our patient clinical appearance, histological examination and associated clinical features led us to the diagnosis of a Buschke-Ollendorff syndrome. The excellent prognosis of this syndrome allowed us to reassure the patient and his family.

REFERENCES

1. Buschke A, Ollendorff H. Ein Fall von Dermatofibrosis lenticularis disseminata and osteopathia condensans disseminata. Derm Wschr 1928; 86: 257-62.

2. Verbov J, Graham R. Buschke-Ollendorff syndrome: disseminated dermatofibrosis with osteopoikilosis. Clin Exp Dermatol 1986; 11: 17-26.

3. Morrison JGL, Wilson Jones E, MacDonald DM. Juvenile elastoma and osteopoikilosis (the Buschke-Ollendorff syndrome). Br J Dermatol 1977; 97: 417-22.

4. Ledoux-Corbusier M, Ahten G, De Dobbeleer G. Juvenile elastoma (Weidmann): an ultrastructural study. J Cutanous Pathol 1981; 8: 219-27.

5. Atherton DJ, Wells RS. Juvenile elastoma and osteopoikilosis (the Buschke-Ollendorff syndrome). Clin Exp Dermatol 1982; 7: 109-13.

6. Smith AD, Waisman M. Connective tissue nevi. Arch Dermatol 1960; 81: 249-52.

7. Danielsen L, Kobayasi T, Jacobsen GK. Ultrastructural changes in disseminated connective tissue nevi. Acta Dermatol Venerol 1977; 57: 93-101.

8. Cole GW, Barr RJ. An elastic tissue defect in dematofibrosis lenticularis disseminata. Arch Dermatol 1982; 118: 44-6.

9. Stieda A. Über umschriebene Knochenverdichtungen im Bereich der Substantia spongiosa im Röntgenbilde. Beiträge zur Klinischen Chirurgie 1905; 45: 700-3.

10. Albers-Schoenberg HE. Eine seltene, bisher nicht bekannte Strukturanomalie des Skelettes. Fortschritte auf dem Gebiet der Roentgenstrahlen 1915; 23: 174-5.

11. Melnick JC. Osteopathia condensans disseminata (osteopoikilosis). Study of a family of four generations. Am J Roentgenol 1959; 82: 229-38.

12. Berlin R, Hedensioe B, Lilja B, Linder L. Osteopoikilosis- a clinical and genetic study. Acta Med Scand 1967; 181: 305-14.

13. Danielson L, Midtgaard K, Christiensen HE. Osteopoikilosis associated with dermatofibrosis lenticularis disseminata. Arch Dermatol 1969; 100: 465-70.

14. Uitto JU, Santa-Cruz DJ, Starcher BC, Whyte MP, Murphy WA. Biochemical and ultrastructural demonstration of elastin accumulation in the skin lesions of the Buschke-Ollendorff syndrome. J Invest Dermatol 1981; 76: 284-7.

15. Giro MG, Duvic M, Smith LT, Kennedy R, Rapini R, Arnett FC, Davidson JM. Buschke-Ollendorff syndrome associated with elevated elastin production by affected skin fibroblasts in culture. J Invest Dermatol 1992; 99: 129-37.

16. Ohnishi Y, Akiyama M, Tajima S, Ishibashi A, Seyama Y. Elastin nevus with normal expression of elastin and elastin-related protein mRNAs. Dermatol 1999; 198: 307-9.

17. Raque CJ, Wood MG. Connective tissue nevus: dermatofibrosis lenticularis disseminata. Arch Dermatol 1970; 102: 390-6.

18. Reinhardt LA, Rountree CB, Wilkin JK. Buschke-Ollendorff syndrome. Cutis 1983; 31: 94-6.

19. Wilson BB, Dent CH, Cooper PH. Papular acnes scars. A common cutaneous finding. Arch Dermatol 1990; 126: 797-800.

20. Balus L, Amantea A, Donati P, Fazio M, Giuliano MC, Bellocci M. Fibroelastolytic papulosis of the neck: a report of 20 cases. Br J Dermatol 1997; 137: 461-6.

21. Schirren H, Schirren CG, Stolz W, Kind P, Plewig G. Papular elastorrhexis: a variant of dermatofibrosis lenticularis disseminata (Buschke-Ollendorff syndrome)? Dermatology 1994; 189: 368-72.

22. Sherer DW, Sapadin AN, Lebwohl MG. Pseudoxanthoma elasticum: an update. Dermatol 1999; 199: 3-7.

23. Blume-Peytavi U, Oudjiel ND, Brand E, Bornfeld N, Hettmannsperger U, Orfanos CE Pseudoxanthoma elasticum: case report and review of the literature. Z Hautkr 1997; 72: 458-63.

24. Sciubba JJ, Niebloom T. Juvenile hyaline fibromatosis (Murray-Puretic-Drescher syndrome): oral and systemic findings in siblings. Oral Surg Oral Med Oral Pathol 1986; 62: 397-409.

25. Costagliola C, Verolino M, Landolfo P, Winkler NR, Mastropasqua L, Landolfo V. Lipoid proteinosis (Urbach-Wiethe disease). Ophthalmol 1999; 213: 392-6.

26. Uitto J, Santa Cruz DJ, Eisen A. Familial cutaneous collagenoma: genetic study on a family. Br J Dermatol 1979; 101: 185-95.

27. Uitto J, Santa-Cruz DJ, Eisen AZ. Connective tissue nevi of the skin: clinical, genetic, and histopathologic classification of hamartomas of the collagen, elastin, and proteoglycan type. J Am Acad Dermatol 1980; 3: 441-61.

28. Limas C. Late onset focal dermal elastosis: a distinct clinicopathologic entity? Am J Dermatopathol 1999; 21: 381-3.

29. Pierard GE, Lapiere CM. Nevi of connective tissue: a reappraisal of their classification. Am J Dermatopathol 1985; 7: 325-33.