Laboratory Studies

Morphologic and biochemical examinations of the blood show that the following values are within the reference range in Winchester syndrome (WS) patients:

White blood cell count
Red blood cell count
Erythrocyte sedimentation rate
Alkaline phosphatase level
Calcium level
Phosphate level
Potassium level
Blood glucose level
Urea concentration
Rheumatoid factor

No specific morphologic or biochemical examinations provide results that are characteristic of Winchester syndrome.

For a better understanding of the nature of this disease, studies should be conducted to assess the urine for abnormal oligosaccharides^[7]and increased para-amino-isobutyric acid, leucine, and proline levels.^[5]

Determinations of IgM serum levels,^{[4, 5]}rheumatoid factor tests, and other examinations are indicated to rule out rheumatoid arthritis.

The organic acid and mucopolysaccharide screening tests of the blood and urine are indicated to exclude mucopolysaccharidoses and mucolipidoses.^[8]

Imaging Studies

Radiologic examination of the skeleton demonstrates generalized osteoporosis with progressive osteolysis in the carpal and tarsal bones. The intensity varies depending on the patient's age and the duration of the disease.

Radiographs of the long bones of the limbs show cortical thinning with widening of the marrow cavity and metaphyses. Also present is flattening of the epiphyses, which have an irregular shape and visible erosions on the surfaces. These changes result in ankylosis of the elbows, knees, and other joints.

Radiographs of the hand bones show osteoporosis of the phalangeal and metacarpal bones, which are enlarged in a cystic manner, with visible destruction of the interphalangeal and metacarpophalangeal joints.

Destructive changes of the hand bones with strong resorption and even osteolysis of the carpal bones and proximal part of the metacarpals can result in ankylosis.^{[2, 3, 4, 9]}

The radiographic changes observed in a 40-year-old female patient included the following: ankylosis between the radius and all the carpal bones, fusion of the carpals and metacarpals, and penciling and resorptive deformities of all the phalanges.^[8]Analogous osteoporotic and osteolytic changes were found in the tarsal, metatarsal, and phalangeal bones.

Intense osteoporosis in the vertebral bodies causes compressive fractures and vertebral curvatures; in the pelvic bones it causes deformation of the plate and hip joints.^{[2, 8]}

A case report documented the progression of radiological findings over a 23-year period.^[40]

Microscopic findings

In biopsy samples of leathery and hyperpigmented skin obtained from children aged 8 and 9.5 years, Cohen et al found characteristic changes in the deeper parts of the skin.^[9]The epidermis is normal, without atrophic changes. An increased amount of melanin was found only in cells of the basal layer. The dermis of the papillary, subpapillary, and medial layers had a mild inflammatory infiltration with features of chronic infection and an increased number of mast cells.

No pathologic changes were found in the collagen fibers. Elastic fibers were numerous. Within the deeper part of the dermis, down to the subcutaneous tissue, a diffuse proliferation of fibroblasts was observed, and collagen bands surrounded the skin appendages without causing their damage. Staining with periodic acid-Schiff (PAS), methylene blue, and colloidal iron did not reveal abnormal mucopolysaccharides or other pathologic substances.^[9]

In the case of the 22-year-old man in whom the disease had a chronic course, a biopsy sample obtained from the upper arm showed a diffuse and somewhat hypocellular and dense homogenization of the collagen that extended from below the reticular dermis to the subdermal adipose tissue.^[9]

Ultrastructural findings

Electron microscopic examinations of fibroblasts obtained from both pathologically changed skin and healthy skin, as well as from hypertrophic gums, showed the following changes: dilated and vacuolated mitochondria, varying amounts of myofilaments in the cytoplasm, and a prominent fibrous nuclear lamina.^[9]The described ultrastructural changes were visible only in fibroblasts. The changes were not found in other cells (eg, endothelial cells, mast cells, marrow cells, chondrocytes).

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Media Gallery

(A) Case 1. Girl aged 2.5 years. Destruction of the carpal ossification centers that have appeared early is visible. (B) Case 1. Girl aged 6 years. The carpals are totally destroyed, and erosion of the proximal metacarpals is seen. The phalanges are expanded and appear cystic. Destructive arthritis is observed in the metacarpal, phalangeal, and interphalangeal joints. (C) Case 1. Girl aged 12 years. Only small portions of the metacarpals remain, and destruction of the phalanges of the fifth finger has occurred. The distal radius and ulna are flared. Courtesy of Patricia Winchester, MD, Departments of Radiology, Pediatrics, and Medicine, Cornell University Medical College and the New York Hospital, Cornell Medical Center, 525 East 68th Street, New York, NY 10021.
Case 1. Girl aged 12 years. The knees are ankylosed. The ends of the long bones are flared. The bone density is markedly diminished. The left distal fibula is eroded. Destruction of the small bones of the foot is seen. Courtesy of Patricia Winchester, MD, Departments of Radiology, Pediatrics, and Medicine, Cornell University Medical College and the New York Hospital, Cornell Medical Center, 525 East 68th Street, New York, NY 10021.

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Table. Clinical Features of Patients with Winchester syndrome^a

Table. Clinical Features of Patients with Winchester syndrome ^a

Clinical Feature	Winchester et al, 1969 ^[2]		Hollister et al, 1974 ^{[3, 4]}			Nabai et al, 1977 ^[5]	Irani et al, 1978 ^[6]	Dunger et al, 1987 ^[7]		Prapanpoch et al, 1992 ^[8]
Clinical Feature	Case 1	Case 2	Case 1	Case 2	Case 3	Case 1	Case 1	Case 1	Case 2^b	Case 1
Sex	F	F	F	F	M	M	M	F	F	F
Age	12 y	3.5 y	9.5 y	8 y	22 y	3 mo	4 y	2	16 y	40 y
Onset	2 mo	1 y	1 y	1 mo	1 y	1 mo	1 y	1 mo	1 y	ND
Consanguinity	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	ND
Skin changes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Coarse face	Yes	Yes	No	No	Yes	Other^c	No	Yes	Yes	Yes
Thickened facial skin	No	No	Yes	Yes	Yes	Yes	No	Yes	No	Yes
Hyperpigmented patches	No	No	Yes	Yes	Yes	Yes	Yes	No	No	No
Skin nodules	No	No	Yes	No	No	No	No	Yes	No	No
Corneal opacity	Yes	Yes	Yes	Yes	Yes	No	No	No	No	Yes^d
Gum hypertrophy	Yes	Yes	Yes	Yes	ND	Yes	No	Yes	Yes	No
Short stature	Yes	Yes	Yes	Yes	Yes	No	ND	Yes	Yes	Yes
Flexion contractures	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Osteoporosis (visible on radiographs)	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Osteolysis of the carpal and tarsal bones	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes
Abnormal test results^e	No	No	No	IgM	IgM	IgM^f	No	Yes^g	Yes^g	No
Patient location	USA	USA	Mexico	Mexico	Mexico	Iran	India	Iran^h	India^h	USA
^a Winter, 1989; completed by Urban. ND indicates no data. ^b Additional clinical details obtained at repeat examination by Winter. ^c Upper lip was hypertrophic. ^d Glaucoma was present. ^e Increased immunoglobulin M (IgM) levels were observed. ^f Increased para-amino-isobutyric acid, leucine, and proline levels in the urine. ^g Abnormal oligosaccharide in the urine. ^h Cases reported in Great Britain.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Janusz E Urban, MD Associate Professor, Head of Division of Pediatric Dermatology, Departments of Dermatology and Venereology, Medical University of Lublin, Poland; Vice-President of Pediatric Dermatology, Polish Dermatology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Albert C Yan, MD Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine

Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology, Society for Pediatric Dermatology, American Academy of Pediatrics

Disclosure: Nothing to disclose.