Dermatofibrosis Lenticularis (Buschke-Ollendorf Syndrome) 

Updated: Jul 18, 2019
Author: Vernon J Forrester, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

Dermatofibrosis lenticularis (Buschke-Ollendorff syndrome) is a rare hereditary disorder of connective tissue. It is inherited as a pleiotropic autosomal dominant trait with incomplete penetrance. This condition was described for the first time in 1902 and was termed "scleroderma adultorum" by Abraham Buschke, and it has gone by several names since, including dermatofibrosis lenticularis disseminata.  Buschke-Ollendorff syndrome is characterized by the presence of sclerotic bone lesions (osteopoikilosis and melorheostosis) in association with connective-tissue nevi (collagenomas and elastomas).[1, 2, 3, 4, 5, 6, 7]

See image below depicting Buschke-Ollendorff syndrome.

Plaque of grouped papular eruptions on the thigh. Plaque of grouped papular eruptions on the thigh.

Pathophysiology

The clinical findings in Buschke-Ollendorff syndrome likely result from abnormal regulation of extracellular matrix components caused by a loss-of-function mutation in the LEM domain–containing protein 3 (LEMD3) gene. LEMD3 normally functions as an inner nuclear membrane protein that antagonizes bone morphogenetic proteins and tumor growth factor-beta signaling pathways.[8] Mutations in LEMD3 lead to abnormal regulation of fibroblasts, which results in an aberrant extracellular matrix with excess elastin and thickened collagen within the dermis.[8] It has been shown that cultured fibroblasts of patients with Buschke-Ollendorff syndrome produce 2-8 times more tropoelastin than fibroblasts of healthy individuals. Elastin production is higher in both involved and uninvolved skin.[9, 10, 11] Elevated elastin mRNA levels support the notion that Buschke-Ollendorff syndrome results from abnormal regulation of extracellular matrix, leading to increased levels of elastin mRNA and increased accumulation of elastin in the dermis. Heterozygous loss-of-function mutations in the LEMD3 gene have been identified in patients with osteopoikilosis without the presence of connective-tissue nevi.[5, 12, 13, 14, 15]

Etiology

This autosomal dominant disorder is caused by a loss of function mutation in LEM domain-containing protein 3 (LEMD3) gene.[1, 4, 5]

Epidemiology

Frequency

Buschke-Ollendorff syndrome is rare syndrome, with an estimated prevalence of 1 in 20,000.[5, 16]

Race

No racial predilection is reported for Buschke-Ollendorff syndrome.[5]

Sex

The incidence is equal for males and females.[5, 16]

Age

Connective-tissue nevi and osteopoikilosis tend to first occur in the preadolescent age (average age, 7 years), but they can be found in neonates just after birth.[16]

Prognosis

In general, Buschke-Ollendorff syndrome follows a benign course. Patients are expected to have a normal lifespan. The associated lesions are generally asymptomatic and begin in childhood. They often persist throughout life and are often found as incidental findings.[17] However, proper diagnosis of this disease and careful documentation of skin and bone lesion locations can help spare the patient from any unnecessary interventions or diagnostic workup.

There have been reports associating Buschke-Ollendorff syndrome with otosclerosis (with resultant hearing impairment), stenosis of the aortae, and diabetes mellitus.[4, 8, 16, 18] Review series have also demonstrated an association of  Buschke-Ollendorff syndrome with cognitive and/or developmental delay, as well as scoliosis and shortened stature.[16]

Patient Education

The patient and/or the patient's family should be educated concerning potential complications and the autosomal dominant inheritance pattern.

 

Presentation

History

History findings in dermatofibrosis lenticularis (Buschke-Ollendorff syndrome) are described below.[1, 4, 5, 15, 19, 20]

The coexistence of connective-tissue nevi, such as elastomas or collagenomas, and skeletal changes, such as osteopoikilosis or melorheostosis, characterize  Buschke-Ollendorff syndrome. As the clinical expression is variable, certain individuals within affected families may not exhibit the full phenotype, and skin and skeletal lesions may occur independently.

Cutaneous lesions typically appear in childhood, but they may first appear in infants or in adults.

Connective-tissue nevi are usually located on the trunk, proximal extremities, and skin folds.

The cutaneous and bone lesions are painless, nonpruritic, and enlarge with the growth of the child.

Reports in the literature have described other dermatologic conditions associated with Buschke-Ollendorff syndrome, including pyoderma gangrenosum, acne, hypertrophic scarring, and hidradenitis suppurativa.[21]

Physical Examination

Physical findings are described below.[1, 3, 4, 5, 19, 20, 22, 23, 24, 25, 26, 27, 28]

Buschke-Ollendorff syndrome is characterized by the presence of connective-tissue nevi and sclerotic bone lesions (osteopoikilosis or melorheostosis). The dermal lesions are composed of collagen, elastin fibers, and, in some instances, glycosaminoglycans. The cutaneous lesions are usually localized on the trunk, in the sacrolumbar region, or symmetrically on the extremities. Occasionally, lesions may be found on the head. They present with slightly elevated and flattened yellowish papules and nodules grouped together forming plaques several centimeters in diameter, as depicted below. The plaques are of irregular shape and sharply demarcated. They are numerous, painless, nonpruritic, and develop over several years.

Plaque of grouped papules on the abdominal coat. Plaque of grouped papules on the abdominal coat.

Other findings in  Buschke-Ollendorff syndrome include nasolacrimal duct obstruction, amblyopia, strabismus, benign lymphoid hyperplasia, hypopigmentation, otosclerosis, and short stature. There is also some suggestion in the literature that it may be associated with cognitive or developmental delay.[16]

The bones demonstrate osteopoikilosis in the stratum spongiosum of the epiphysis and the metaphysis of the long bones, especially in the fingers, ulna, and radius. Focal bone densities are often present in the carpal bones, metacarpal bones, and phalanges. They also occur in the lumbosacral spine. Each focal area of density may measure from 1-16 mm in length. Other forms of osteosclerosis, including osteopathia striata, melorheostosis, and mixed sclerosis bone dystrophy, may be present. See the image below.

Small longitudinal lesions of increased bone densi Small longitudinal lesions of increased bone density in the proximal epiphysis of the left tibial bone and in the distal epiphysis of the right tibial bone.

Congenital spinal stenosis, disk herniation, clubfoot deformity, and nerve root compression may be present.

Otosclerosis with or without hearing loss may occur. It is caused by bone resorption and redeposition, and it may be clinically asymptomatic; however, otosclerosis is a rare phenomenon in patients with  Buschke-Ollendorff syndrome.

Complications

Complications can include the following[4, 8, 18] :

  • Bone malignancy - Osteosarcoma, chondrosarcoma, giant cell tumor
  • Hearing impairment
  • Stenosis of the aortae
  • Diabetes
 

DDx

Diagnostic Considerations

Connective-tissue nevi can occur sporadically or as part of an inherited or congenital disorder such as tuberous sclerosis (shagreen patch), Proteus syndrome, and multiple endocrine neoplasia type 1. The differential diagnosis also includes disseminated nevus anelasticus.

In the absence of osteopoikilosis, familial cutaneous collagenoma, juvenile elastoma, or eruptive collagenoma may be considered. Lack of LEMD3 gene mutation allows for differentiation.[29] Connective-tissue nevi can also occur sporadically

The differential diagnosis of osteopoikilosis includes osteopathia striata, melorheostosis, bone metastases,[30] tuberous sclerosis (see Tuberous Sclerosis), osteomas (Osteoma Cutis), and mastocytosis (Mastocytosis).

Differential Diagnoses

 

Workup

Laboratory Studies

Patients suspected of having dermatofibrosis lenticularis (Buschke-Ollendorff syndrome) should undergo genetic testing, given the highly variable phenotypic expression.[16]

Imaging Studies

Consider the following the information below with regard to imaging studies.[1, 2, 4, 5, 27, 31]

In Buschke-Ollendorff syndrome, the radiographic appearance of osteopoikilosis is diagnostic. Bone densities are often present in the fingers, carpal and metacarpal bones, lumbosacral spine, and tibial and radial bones. They are sclerotic circular or ovoid lesions symmetrically distributed in a periarticular location, and they may be 1-16 mm in diameter. Lesions can increase or decrease in size and number or even disappear in serial radiographs. The bone densities are caused by condensations of the spongiosa.

Other sclerosing dysplasias, including osteopathia striata, melorheostosis, and focal sclerosis, can be seen. When osteopoikilosis is seen in combination with these sclerosing dysplasias, the term mixed sclerosing bone dystrophy is used.

Lesions do not have increased bone radiotracer uptake.

T1-weighted MRI reveals multiple, well-circumscribed, low-signal foci usually in a symmetric distribution. The differential diagnosis includes blastic metastases, tuberous sclerosis, and mastocytosis. However, symmetry and uniform size of the lesions would be most suggestive of osteopoikilosis.

Histologic Findings

Regarding skin lesions, histopathologic examination reveals numerous thickened collagen fibers in the dermis. Orcein stain of the reticular layer of the dermis reveals numerous elastic fibers with various diameters as depicted below. These fibers are frequently fragmented, and, in some places, they create a net of bundles. Weigert stain of the reticular dermis also reveals numerous elastic fibers with different diameters as shown below.[10] While most lesions have mixed findings, they can be categorized into four subtypes based on their composition: pure collagenoma, pure elastoma, mixed connective-tissue nevi, and cellular connective-tissue nevi.[15]

Orcein stain of elastic fibers shows the histopath Orcein stain of elastic fibers shows the histopathologic features of the skin lesions.
Weigert stain of the elastic fibers shows the hist Weigert stain of the elastic fibers shows the histopathologic features of the skin lesions.
Hematoxylin and eosin stain shows the histopatholo Hematoxylin and eosin stain shows the histopathologic features of the skin lesions.
 

Treatment

Surgical Care

Surgical excision of the dermal lesions is indicated only for cosmetic reasons. In some patients, surgical treatment of deafness is possible. Surgical treatment of associated conditions, such as stenosis of the aortae, should be performed as appropriate.

Consultations

Note the following potential consultations:

  • Laryngologic examination with audiogram

  • Ophthalmologic examination with ophthalmoscopy

  • General physical examination with ECG

Activity

Osteopoikilosis is asymptomatic; however, 15-20% of patients experience pain and joint effusions. Usually, no special restrictions in activity are required.[5]

Long-Term Monitoring

There are no specific follow-up requirements in the case of asymptomatic dermatofibrosis lenticularis (Buschke-Ollendorff syndrome).