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Basic Principles of Genetics

Introduction The completion of the human genome sequence, with an estimated size of 3.2 gigabases (Gb) and containing ~20 000–25 000 genes , represents a powerful tool in medicine that facilitates the identification of disease-associated genes. Detailed information on human sequence variation and advanced technologies for its detection have broadened our knowledge of the genetic basis of human disease. The pathogenesis of many disorders also involves epigenetics, which…

Dermatologic Manifestations in Patients with Systemic Disease

Key features ▪ Because of the frequency of skin involvement in systemic diseases, cutaneous manifestations often prove helpful in establishing the correct diagnosis ▪ Skin signs of systemic disease can be specific, e.g. cutaneous lupus, cutaneous sarcoidosis, in part because of associated histologic features, while others are best described as suggestive, e.g. pyoderma gangrenosum, acquired ichthyosis ▪ Cutaneous disease can serve as the initial manifestation of…

Graft-versus-Host Disease

Key features ▪ Currently, over 25 000 allogeneic hematopoietic stem cell transplants (HSCTs) are performed worldwide each year ▪ Trends in the use of unrelated donors, non-myeloablative conditioning protocols, and donor lymphocyte infusions are impacting the incidence and presentation of graft-versus-host disease (GVHD) ▪ Acute GVHD is a major complication of allogeneic HSCT; severe skin involvement, although uncommon, is associated with a high mortality rate ▪ Chronic…

Nutritional Diseases

Key features ■ Nutritional deficiencies may affect any organ system, including the skin, which may provide clues to the diagnosis ■ The two classic protein–energy malnutrition syndromes are kwashiorkor and marasmus ■ In addition to inadequate oral intake, there are secondary causes of nutritional deficiencies, e.g. intestinal malabsorption due to medical conditions or surgical procedures ■ Vitamin and trace element deficiencies can lead to a wide…

Calcifying and Ossifying Disorders of the Skin

Synonyms ▪ Calcinosis cutis: cutaneous calcification ▪ Osteoma cutis: cutaneous ossification ▪ Calciphylaxis: calcific uremic arteriolopathy; calcifying panniculitis; uremic gangrene syndrome ▪ Subepidermal calcified nodule: solitary congenital nodular calcification; Winer's nodular calcinosis Key features ▪ Calcium regulates several key physiologic events in the skin, including epidermal proliferation, differentiation, and cell–cell adhesion ▪ Disruption of normal calcium regulatory pathways can lead to calcification and/or ossification of the…

Porphyria

Key features ▪ The porphyrias result from dysfunction of enzymes involved in heme biosynthesis ▪ The different types can be classified into either acute versus non-acute or cutaneous versus non-cutaneous forms ▪ Cutaneous symptoms exclusively involve sun-exposed areas of the body ▪ Life-threatening neurologic attacks can occur in the acute porphyrias ▪ Diagnosis of specific types of porphyria may at times be difficult because clinical symptoms…

Deposition Diseases

Introduction The cutaneous deposition disorders are a heterogeneous group of conditions characterized by the presence of primarily endogenous substances within the dermis or the subcutis. Deposition disorders can be associated with localized or generalized cutaneous findings, and skin involvement is sometimes the earliest sign of a deposition disease. Histologic examination of cutaneous lesions, with the use of special stains including immunohistochemistry, is a very helpful diagnostic…

Amyloidosis

Synonyms ▪ Primary systemic amyloidosis – AL amyloidosis ▪ Secondary systemic amyloidosis – AA amyloidosis Subtypes ▪ Primary cutaneous amyloidosis – macular amyloidosis, friction amyloidosis, lichen amyloidosis (lichen amyloidosus), biphasic amyloidosis, dyschromic amyloidosis, nodular amyloidosis Key features ▪ Characteristic properties of amyloid include congophilia and green birefringence under polarized light, a distinctive fibrillar ultrastructure, and a cross-β-pleated sheet configuration by X-ray crystallography ▪ The three major…

Mucinoses

Key features ▪ The cutaneous mucinoses are a heterogeneous group of disorders in which an abnormal amount of mucin accumulates in the skin ▪ The etiopathogenesis of cutaneous mucinoses is unknown ▪ The cutaneous mucinoses are divided into two groups: (1) primary cutaneous mucinoses, in which the mucin deposition leads to clinically distinctive lesions and is the major histologic feature; and (2) secondary mucinoses, in which…

Other Rheumatologic Disorders and Autoinflammatory Diseases

Although all the disorders in this chapter represent inflammatory systemic diseases, there are two major groups based upon underlying pathomechanisms. Disorders such as systemic-onset juvenile idiopathic arthritis (Still disease) and inherited autoinflammatory diseases are related to abnormalities in the innate immune system whereas other disorders, including rheumatoid arthritis and Sjögren syndrome, are characterized by autoimmune-mediated tissue damage via autoreactive antigen-specific T cells and the presence of…

Morphea and Lichen Sclerosus

Morphea and lichen sclerosus are inflammatory skin diseases that ultimately evolve into two distinct modes of cutaneous sclerosis. In morphea, there is inflammation of the dermis that may extend into subcutaneous structures. Lichen sclerosus is primarily a disease of the genital mucosa (and less often extragenital sites) that affects the epidermis and the dermis. Although morphea may lead to joint contractures and atrophy of underlying muscle,…

Systemic Sclerosis (Scleroderma) and Related Disorders

Systemic Sclerosis Synonyms Systemic sclerosis: ▪ Scleroderma ▪ Progressive systemic sclerosis Subtypes of cutaneous involvement: ▪ Diffuse ▪ Limited (includes CREST syndrome) Key features ▪ An uncommon autoimmune connective tissue disease of unknown etiology ▪ Characterized by symmetric hardening of the skin of the fingers, hands and face that may generalize ▪ Raynaud phenomenon is common and digital ulcers may develop ▪ Internal organ involvement is…

Dermatomyositis

Synonyms ■ Dermatomyositis ■ Idiopathic inflammatory myopathies ■ Idiopathic inflammatory dermatomyopathies Key features ■ Autoimmune connective tissue disease of uncertain etiology demonstrating a bimodal age distribution with both juvenile and adult forms ■ Clinical and laboratory signs of proximal extensor inflammatory myopathy ■ Distinctive, photodistributed, pink–violet poikiloderma favoring the scalp, periocular region, and extensor surfaces, in addition to distinctive nail-fold changes and pink–violet papules overlying the…

Lupus Erythematosus

Synonyms/variants ▪ Discoid lupus erythematosus: a subset of chronic cutaneous lupus erythematosus ▪ Lupus profundus: a variant of lupus panniculitis ▪ Lupus erythematosus tumidus: tumid lupus Key features ▪ There are several variants of cutaneous lupus, defined in part by the location and depth of the inflammatory infiltrate ▪ Acute cutaneous lupus involves primarily the epidermis and upper dermis and is usually associated with active systemic…

Autoantibodies Encountered in Patients with Autoimmune Connective Tissue Diseases

Key features ▪ Autoantibodies can be of significant value in the diagnosis, management, and prognosis of autoimmune connective tissue diseases (AI-CTDs), but their interpretation depends on the type of autoantibody and the specific AI-CTD ▪ The classic ANA assay remains the entrée into the world of AI-CTD serology, and understanding its limitations is critical to clinical decision making ▪ The evolution of clinical immunology laboratory technology…

Diseases of the Eccrine and Apocrine Sweat Glands

Sweat Glands Eccrine Sweat Glands Key features ▪ 2–5 million eccrine glands are unevenly distributed over the skin surface ▪ In healthy individuals, eccrine sweat is 99% water ▪ Sweating is a reflex sympathetic autonomic function mediated by cholinergic neurons In humans, sweating is essential for thermoregulatory homeostasis. There are two main mechanisms for cooling the body: radiative cooling via cutaneous vasodilation and evaporative cooling via…

Folliculitis and Other Follicular Disorders

Introduction This chapter will review both superficial and deep forms of folliculitis as well as disorders of follicular keratinization and the follicular occlusion tetrad (acne conglobata, hidradenitis suppurativa, dissecting cellulitis, and pilonidal sinus). Examples of superficial folliculitis include those due to Staphylococcus aureus or Pseudomonas aeruginosa infections, whereas acne keloidalis and pseudofolliculitis barbae are examples of deep forms. The disorders of follicular keratinization represent a varied…

Rosacea and Related Disorders

Introduction The term “ rosacea ” encompasses a constellation of clinical findings, with the key components being persistent facial erythema and inflammatory papulopustules. Additional features are facial telangiectasias, a tendency for frequent facial flushing (sometimes referred to as “pre-rosacea”), non-pitting facial edema with erythema, ocular inflammation, and phymatous changes. The latter predominantly affect the nose and rarely the ears, forehead, chin, or eyelids. In 2002, rosacea…

Acne Vulgaris

Synonym ▪ Acne Key features ▪ A multifactorial disorder of the pilosebaceous unit ▪ Significant psychologic and economic impact ▪ Clinically characterized by comedones, papules, pustules, cysts, and potential scarring Introduction Acne vulgaris is a multifactorial disorder of the pilosebaceous unit. The clinical picture can vary significantly, from mild comedonal acne to fulminant systemic disease. Although all age groups may be affected by its many variants,…

Structure and Function of Eccrine, Apocrine and Sebaceous Glands

Eccrine, Apocrine, and Apoeccrine Sweat Glands Key features ▪ Eccrine sweat glands are activated by emotional and thermal stimuli and are necessary for thermoregulation; they have a generalized distribution, with the highest density on the palms and soles ▪ The eccrine secretory unit consists of a coiled secretory portion that drains into a long thin duct whose apical portion (acrosyringium) opens to the skin surface ▪…