Contents << Previous Chapter Next Chapter >> Search


This connective tissue disorder usually appears at birth or develops at any age up to the third year.

Clinical Features

Skin lesions are characterized by firm, smooth, pink or flesh colored nodules, which are found on one or more fingers or toes. The thumbs and great toes are spared. The swellings, which are firmly attached to the skin, are usually on the extensor aspect or the side of the terminal phalanges. Spontaneous regression usually occurs within two years.



This is an invasive calcifying tumor of the palms and soles with a unique histological pattern, occurring usually in young children as firm, fixed, fibrous nodules.


(Infantile Systemic Hyalinosis)

This syndrome affects infants in the first weeks of life, causing limitation of joint mobility with diffuse thickening of the joints and hyaline tissue deposit. General manifestations: gingival hypertrophy, subcutaneous nodules of the perianal, lips, and ears.

Systemic manifestations: diarrhea, growth failure, recurrent infections may accompany the syndrome.



This hereditary connective tissue disorder appears in early infancy and is characterized by mild hirsutism, limitation of joint mobility and localized areas of stony-hard skin. The condition affects the deeper skin and fascia which is much thicker than normal and tends to be most pronounced in the buttocks and legs.



All the premature aging syndromes are probably inherited, though the defect may not be obvious in the first few years of life.

Clinical Features

Skin changes :

Loss of cutaneous fat leading to atrophy and wrinkling.


Hair loss.

Nail dystrophy.

Defective pigmentation.

Poikiloderma, sclerosis and ulceration.

Different syndromes associated with premature aging are:

  1. Inherited syndromes:




  2. Congenital progeroid syndromes:

    Down‘s syndrome

    Neonatal pseudo-hydrocephalic progeroid syndrome


    Osteodysplastic Xeroderma

    Wrinkly skin syndrome

    Familial mandibulo-acral dysplasia.

  3. Excessive exposure to irradiation (usually UVR).

  4. Photosensitivity, especially congenital, e.g. poikiloderma congenitale, xeroderma pigmentosum, Cockayne‘s syndrome.

  5. Diseases causing elastolysis, e.g. cutis laxa.

  6. Thickened immobile skin, e.g. diabetic cheiroarthropathy.

  7. Fragile skin, e.g. prolidase deficiency.

Loss of subcutaneous fat e.g. generalized lipodystrophy.


(Donohue‘s syndrome)

This is an inherited syndrome that begins early after birth and is characterized by resistence to insulin. The defect is in the receptor binding, post receptor or in both. Fibroblasts respond poorly to the metabolic actions of insulin and to the actions of several other growth factors as epidermal growth factor.

Clinical Features

The child is abnormal at birth with low birth weight and the disease is usually fatal.

Growth is generally retarded, the nutritional status remains poor and susceptibility to infection is high.

The skin appears too large for the body, loosely folded at the flexures, and may be corrugated with gyrate folds on the hands and feet, which may be disproportionately large.

Hypertrichosis of the forehead and cheeks.

Progressive muscle wasting.

The bone age is retarded and there may be metaphyseal and epiphyseal dystrophy.

The nose is broad, the ears are low set and large.

The eyes are widely spaced.

The breasts and the penis or clitoris may be slightly hypertrophic.


(Adult premature aging syndrome)

Clinical Manifestations

The earliest manifestations of the syndrome are:

Graying at the temples

Skin manifestations: the skin becomes tense, shining and adherent. The lower legs and feet, forearms and hands are most severely involved and to less extent the face and neck.

Keratoses and ulcers: over pressure points on the feet and ankles.

Pigmentation: mottled or diffuse and telangiectasia are often conspicuous on the limbs, face and neck.

Subcutaneous tissue: loss of subcutaneous tissue results in a bird-like faces and thin spindly legs, which contrast with the normal or obese trunk.

Joints: become fixed and there may be sclerodactaly and acral gangrene.

The voice: may be high pitched and hoarse from thinning of the cords and fixation of the epiglottis.

Intelligence is usually normal.

Endocrine changes: small stature and hypogonadal, with sparse or absent pubic and axillary hair.

Diabetes: This type is characterized by relatively low blood glucose levels and peripheral resistance to insulin.

Eye changes: Cataracts develop between the ages of 20 and 35 in most cases and are usually posterior and subcapsular. Other ocular defects may occur.

Malignancy: fibrosarcomas, which occur in 10% of patients. Carcinoma has developed in a chronic leg ulcer.

Blood vessels: atheroma develops early.

Death usually occurs in fourth to sixth decade, due to myocardial infarction or malignancy.


The disease has characteristic clinical features with multi-systems involvement.

The radiological changes are often striking. There may be calcification of arteries, ligaments, tendons and subcutaneous tissue with osteoporosis of the extremities, especially the legs.


(Hutchinson-Gilford syndrome)

This is an autosomal recessive syndrome where fibroblast survival time is decreased with increased production of hyaluronic acid that appears in urine.

Clinical Manifestations

General features

Affected children usually appear normal at birth.

In the first year the infant manifests with retarded growth.

In the second year there is growth failure with reduced subcutaneous fat on the face and limbs.

Prominent eyes and scalps veins, bird facial appearance, peaked nose and centrofacial cyanosis.

Micrognathia and thin lips, large cranium with patent fontanels and frontal bossing.

Skin manifestations

Thin, taut and shiny skin in some areas but lax and finely wrinkled in others.

Hair changes: Thin hair and alopecia may develop.

Sweat glands: Hypohidrosis due to decreased eccrine sweat glands.

The veins are prominent and there may be easy bruising.

Fig. 303. Progeria

After several years the manifestations are:

Hyperpigmentation: progressive mottled hyperpigmentation develops, most marked on exposed sites, but there is no photosensitivity.

Thickened sclerotic areas: may be present on the lower trunk or thighs and in one case multiple keloids developed on the hands and arms .

Nails: are usually small, thin and dystrophic. Koilonychia and onychogryphosis may occur.

Teeth: The dentition is abnormal and delayed. There may be skeletal abnormalities, such as dystrophic clavicles and coxa vulga and joint contractures.

Nipples: may be hypoplastic.

Bone resorption: may lead to frequent fractures .

Sexual maturation : is absent.

Intelligence is normal.

Death usually occurs in the second decade as a result of severe generalized atheroma.



Acrogeria is characterized by cutaneous atrophy and loss of subcutaneous fat particularly over the distal extremities, leading to premature aging of the extremities. Acrogeria begins at birth, where the general health and life expectancy are normal.

Clinical Manifestations

Short stature and low birth weight.

The skin becomes dry, thin, transparent and wrinkled, especially over the hands.

Poikiloderma and telangiectasia and easy bruising due to prominent veins as a result of lack of the supporting subcutaneous fat.

The hands and feet may be very small.

The face appears ‘pinched‘, with a hollow-cheek ‘owl-eyed‘ appearance, with a beaked nose and thin lips.

Micrognathism may be present.

Premature senility due to lack of subcutaneous fat.

Nails may be atrophic or thickened.



The manifestation of this rare familial syndrome appears at birth. The cause is unknown, where the dermal collagen and elastin appear normal on light microscopy.

Clinical Manifestations

Skin manifestations

Dry wrinkled skin of the hands, feet and ventral surfaces of the trunk.

General manifestations

The veins are unduly prominent.

There may be also mental retardation, ocular defects and poor muscle tone.



Skin of diabetics may show different changes mainly: Thick, tight waxy skin, limited joint mobility, frozen shoulder and Dupuytren‘s contracture. The “prayer sign“ in which the patient tries to oppose the two palms provides an easy screening test.

Retinal and renal disease due to microvascular damage.

The histology of the skin changes resembles systemic sclerosis. The difference is a large collagen fibers, thickening of the capillary basement membrane and increased mucin.



Perforating dermatoses include different types of skin diseases in which some tissue protrudes from the dermis. The manifestations of this syndrome are due to defect in collagen, elastic tissue or defect in the epidermal keratinocytes.

The extruded materials may show inflammatory cells, red cells, microorganisms and extracellular substances, such as mucin or altered connective tissue components.

  1. Primary perforating dermatoses

    These include the following types:

    Reactive perforating collagenosis

    Perforating folliculitis

    Reactive perforating folliculitis (Kyrle‘s disease)

    Perforating serpiginous dermatoses.

  2. Secondary perforating dermatoses:

    The condition is secondary to an underlying disease, such as granuloma annulare or pseudoxanthoma elasticum.

    Perforating dermatoses secondary to exogenous factors include:

    Chemicals applied to the skin topically or by intradermal injection of medications such as steroids may lead to perforating disease.

Reactive Perforating Collagenosis

The condition usually starts in early childhood.

Clinical Features

The primary lesion is skin colored small papules, which increase in size within one month to about half centimeter and then become umbulicated with keratinous plug. The lesions regress within two months leaving slight scarring or hypopigmentation. The lesions may recur again, can be elicited by trauma as a linear lesion, or can be produced in response to cold and regress by warming the area.


Topical retinoids may reduce the number of lesions.

Oral isotretinoin, methotrexate, emollient creams, topical steroids under occlusion may help some cases.

Perforating serpengious elastosis

The age of onset ranges from 6 to 20 years.

Clinical Manifestations

Small horny or umbulicated papules appear mainly on the back, sides of the neck, cheek and arms. Skin lesions may be unilateral or bilateral and symmetrical.

The lesions are characteristically arranged in lines, circles or segments of circles in a serpiginous pattern. The individual papules may remain small or may enlarge slightly to assume a crateriform appearance with an elevated edge and a central plug, which may leave an area of atrophic skin surrounded by smaller papules, each with a horny plug.

The lesions may persist for several years but eventually involute spontaneously to leave reticulate atrophic scars, which is liable for keloid transformation.



Colloid milium or colloid degeneration of the skin is a degenerative skin changes, characterized clinically by the development of yellowish, translucent papules or plaques on light-exposed skin and histologically by the presence of colloid in the dermal papillae.

In young children, the lesions are often confined to the face, around the orbits, the backs of the hands, the back and sides of the neck and the ears, with diffuse infiltration surmounted by innumerable small papules, which may appear vesicular.

Clinical features

The primary lesions are small dermal papules 1-2 mm in diameter, yellowish-brown and sometimes translucent, develop slowly and more or less symmetrically in irregular groups in areas exposed to sunlight. They feel soft and may release their gelatinous contents when punctured.

Fig. 304. Milia

In older patients the papules are often fewer, larger and their potential distribution is much wider, although often only one or two sites are involved in each individual.


CO2 laser ablation of the extensive lesions may give better cosmetic results. Superficial resurfacing by Co2 laser using topical anaesthetics as Emla creams

Dermabrasion, diathermy and cryotherapy, can also give good results.



  1. Simons-Ling N, Schachner L, Penneys N et al. Childhood systemic lupus erythematosus. Arch Dermatol 1983; 119: 491-4.

  2. Ansell BM. Perspectives in pediatric systemic lupus erythematosus. J Rheumatol 1987; 14: 177-9.

  3. Cummings NP, Hansen J, Hollister JR. Systemic lupus erythematosus in a premature infant. Arthritis Rheum 1985; 28: 573-5.

  4. Kettler AH, Bean SF, Duffy JO et al. Systemic lupus erythematosus presenting as a bullous eruption in a child. Arch Dermatol 1988; 124: 1083-7.

  5. Baguley E, Maclachlan N, Hughes GRV. SLE and pregnancy. Clin Exp Rheumatol 1988; 6: 183-5. Olansky AJ, Briggaman RA, Gammon WR et al. Bullous systemic lupus erythematosus. J Am Acad Dermatol 1982; 7: 511-20.

  6. Wojnarowska F, Marsden RA, Bhogal B et al. Chronic bullous disease of childhood, childhood cicatricial pemphigoid and linear IgA disease of adults. J Am Acad Dermatol 1988; 19: 792-805.

  7. Jacoby RA, Abraham AA. Bullous dermatosis and systemic lupus erythematosus in a 15-year-old boy. Arch Dermatol 1979; 115: 1094-97.

  8. Hall RP, Lawley TJ, Katz SI. Bullous eruption of systemic lupus erythematosus. J Am Acad Dermatol 1982; 7: 797-9.

  9. Wojnarowska F, Marsden RA, McKee PH et al. A comparative study of benign chronic bullous dermatosis of childhood and linear IgA dermatosis of adults. Br J Dermatol 1985; 113 (Suppl. 29): 17-19.

  10. Marsden RA, McKee PH, Bhogal B et al. A study of benign chronic bullous dermatosis of childhood and comparison with dermatitis herpetiformis and bullous pemphigoid occurring in childhood. Clin Exp Dermatol 1980; 5: 159-76.

  11. Hayslett JP. Effect of pregnancy in patients with SLE. Am J Kidney Dis 1982; 2 (Suppl. 1): 223-8.

  12. Jackson R, Gulliver M. Neonatal lupus erythematosus progressing into systemic lupus erythematosus. Br J Dermatol 1979; 101: 81-6.

  13. Lockshin MD, Bonfa E, Elkon K et al. Neonatal lupus risk to newborns of mothers with systemic lupus erythematosus. Arthritis Rheum 1988; 31: 697-701.

  14. Provost TT, Watson R, Gaitherk K et al. The neonatal lupus erythematosus syndrome. J Rheumatol 1987; 14: 199-205.

  15. Ansell BM. Perspectives in pediatric systemic lupus erythematosus. J Rheumatol 1987; 14: 177-9.

  16. Cummings NP, Hansen J, Hollister JR. Systemic lupus erythematosus in a premature infant. Arthritis Rheum 1985; 28: 573-5.

  17. Wallace DJ, Dubois EL, eds. Dubois‘ Systemic Lupus Erythematosus 3rd edn. Philadelphia: Lee & Febiger, 1987.

  18. Burge SM, Frith PA, Juniper RP et al. Mucosal involvement in systemic and chronic cutaneous lupus erythematosus. Br J Dermatol 1989; 121: 727-41.

  19. Potasman I, Bass HM. Multiple tendon rupture in systemic lupus erythematosus: case report and review of the literature. Ann Rheum Dis 1984; 43: 347-8.

  20. Powell FC, Greipp PR, Su WPD. Discoid lupus erythematosus and monoclonal gammopathy. Br J Dermatol 1983; 109: 355-60.

  21. Williams REA, O‘Keefe R, Mackie RM et al. The contributions of direct immunofluorescence (DIF) to the diagnosis of lupus erythematosus. Br J Dermatol 1988; 119: 520.

  22. Beck JS, Rowell NR. Discoid lupus erythematosus. Quart J Med 1966; 35: 119-36.

  23. HA, Klippel JH, Balow JE et al. Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986; 314: 614-19.

  24. Elliott RW, Essenhigh DM, Morley AR. Cyclophosphamide treatment of systemic lupus erythematosus. Br Med J 1982; 284: 1160-1.

  25. Plat JL, Burke BA, Fish AJ et al. Systemic lupus erythematosus in the first 2 decades of life. Am J Kidney Dis 1982; 2 (Suppl. 1): 212-22.

  26. Fretzin DF, Esterley NB. The fibromatoses. In: Moschella SL, eds. Dermatology Update. New York: Elsevier, 1982:253-84

  27. Rao BN. Challenges in the treatment of childhood fibromatosis. Arch Surg 1987; 122: 1296-8.

  28. Chung EB, Enzinger FM. Infantile myofibromatosis. Cancer 1981; 48: 1807-18.

  29. Fletcher CM, Achu P, van Noordens et al. Infantile myofibromatosis: a light microscopic, histochemical and Immunohistochemical study suggesting true smooth muscle differentiation. Histopathology 1987; 11: 245-58.

  30. Goldberg NS, Bauer BS, Kraus H et al. Infantile myofibromatosis: a review of clinicopathology, with perspectives on new treatment choices. Pediatr Dermatol 1988; 5: 37-46.

  31. Molnar P, Olah E, Miko TL et al. Aggressive infantile myofibromatosis. Report of a case of progressive congenital multiple fibromatosis. Med Paediatr Oncol 1986; 14: 332-7.

  32. Rosenberg HS, Stenback WA, Spjut HT et al. The fibromatoses of infancy and childhood. Perspect Pediatr Pathol 1978; 4: 269-384.

  33. Wiswell TE, Davis J, Cunningham BE et al. Infantile myofibromatosis: the commonest fibrous tumour of infancy. J Pediatr Surg 1988; 23: 315-18.

  34. Enzinger FM, Weiss SW. Fibrous proliferations of infancy and childhood. In: Enzinger FM, ed. Soft Tissue Tumors 2nd edn. St Louis: Mosby, 1988: 164-222.

  35. Paller AS. Fibrous hamartoma of infancy. Eight additional cases and a review of the literature. Arch Dermatol 1989; 125: 88-91.

  36. Chitale AR, Murthy AK, Maniar JK et al. Juvenile hyaline fibromatosis. Ultrastruct Pathol 1987; 11: 771-5.

  37. Landing BH, Nadorra R. Infantile systemic hyalinosis. Pediatr Pathol 1986; 6: 55-97.

  38. Coskey RJ, Dalney KW. Recurring digital fibrous tumor of childhood: review of the literature. J Pediatr Orthol 1986; 6: 612-17.

  39. Ryman W, Bale P. Recurring digital fibromas of infancy. Austr J Dermatol 1985; 26: 113-17.

  40. Esterley NB, McKusick VA. Stiff skin syndrome. Pediatrics 1971; 47: 360-9.

  41. Beauregard S, Gilchrest BA. Syndromes of premature ageing. Dermatol Clin 1987; 5: 109-21.

  42. Cohen JI, Arnett EN, Kolodny AL et al. Cardiovascular features of the Werner syndrome. Am J Cardiol 1987; 59:493-5.

  43. Epstein CJ, Martin GM, Schultz AL et al. Werner‘s syndrome: a review. Medicine 1966; 45: 177-221.

  44. Kuzuya H, Imura H. Insulin resistance associated with congenital disorders. Insulin receptors in Werner‘s syndrome, myotonic dystrophy and type A extreme insulin resistance. Jap J Med 1988; 27: 219-21.

  45. Salk D. Werner‘s syndrome: a review of recent research. Hum Genet 1982; 62: 1-15.

  46. Salk D et al. Werner‘s syndrome and human ageing. New York: Plenum Press, 1985.

  47. Vannini P, Ciavarella A, Forlani G et al. Investigation of insulin resistance associated with Werner‘s syndrome. Diabet Metab 1987; 13: 81-5.

  48. Badame AJ. Progeria. Arch Dermatol 1989; 125: 540-4.

  49. Brown WT, Zebrower M, Kieras FJ et al. Progeria, a model disease for the study of premature ageing. Basic Life Sci 1985; 35: 375-96.

  50. Hamer L, Kaplan F, Fallon M et al. The musculoskeletal manifestations of progeria. A literature review. Orthopedics 1988; 11: 763-9.

  51. De Groot WP, Tafelkruyer J, Woerdemann MJ et al. Familial acrogeria (Gottron). Br J Dermatol 1980; 103: 213-23.

  52. Venencie PY, Powell FC, Winkelmann RK et al. Acrogeria with perforating elastoma and bony abnormalities. Acta Derm Venereol 1984; 64: 348-51.

  53. Snigula F, Rautenstrauch T. A new neonatal progeroid syndrome. Eur J Pediatr 1981; 136: 325-4. 

  54. Gazit E, Goodman RM, Katznelson MB et al. Wrinkly skin syndrome. Clin Genet 1973; 4: 186.

  55. Rosenbloom AL, Silverstein JH. Limited joint mobility in childhood diabetes mellitus. New Engl J Med 1981; 305: 191-4.

  56. Kaplowitz PB, D‘Ercole J. Fibroblasts from a patient with leprechaunism are resistant to insulin, epidermal growth factor and somatomedin C. J Clin Endocr Metab 1982; 55: 741.

  57. Patterson JH, Watkins WL. Leprechaunism in a male infant. J Pediatr 1962; 60: 730-9.

  58. Patterson JW. The perforating disorders. J Am Acad Dermatol 1984; 10: 561-81.

  59. Goette DK. Transepidermal elimination of altered collagen after intralesional adrenal steroid injections. Arch Dermatol 1984; 120: 539-40.

  60. Katz R, Hood AF. Transepidermal elimination following the use of a topical adrenal steroid. Arch Dermatol 1985; 121:412-13

  61. Patterson JW. The perforating disorders. J Am Acad Dermatol 1984; 10: 561-81.

  62. Serrano G, Aliaga A, Lorente M et al. Reactive perforating collagenosis responsive to PUVA. Int J Dermatol 1988; 27: 118-19.

  63. Ayala F, Donofrio P. Elastosis perforans serpiginosa: Report of a family. Dermatologica 1983; 166: 32.

  64. Light N, Meyrick-Thomas RH, Stephens A et al. Collagen and elastin changes in d-penicillamine-induced pseudoxanthoma elasticum-like skin. Br J Dermatol 1986; 114: 381-8.

  65. Apfelberg DB, Druker D, Spence B et al. Treatment of colloid milium of the hand by dermabrasion. J Hand Surg 1978; 3: 98-100.

  66. Findlay GH, Morrison JGL, Simson IW et al. Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams. Br J Dermatol 1975; 93: 613-22.

  67. Hashimoto K, Black M. Colloid milium; A final degeneration product of actinic elastoid. J Cutan Pathol 1985; 12: 147-56.
| Top
Contents << Previous Chapter Next Chapter >> Search