Inflammatory versus neoplastic

An early and major “branch point” in classifying skin diseases is deciding simply if a skin condition is “neoplastic” (either benign or malignant) or “inflammatory” (either infectious or non-infectious) (see Fig. 0.1 ). However, an experienced clinician knows that one must consider possible diagnoses along multiple limbs before narrowing the differential diagnosis, because both overlap and mimicry can occur. For example, mycosis fungoides, the most common form of cutaneous T-cell lymphoma, is a clonal lymphoproliferative disorder (a “neoplasm”), yet its clinical presentation resembles an inflammatory disorder ( Fig. 0.2 ), especially in its early stages. Conversely, sarcoidosis is an inflammatory condition, but it may present as an isolated infiltrated plaque or nodule that may mimic a neoplasm ( Fig. 0.3 ).

Mycosis fungoides, the most common form of cutaneous T-cell lymphoma.

Mycosis fungoides represents a neoplastic proliferation of monoclonal lymphocytes, but it presents clinically in a manner akin to that of inflammatory disorders.

Courtesy, Lorenzo Cerroni, MD.

Sarcoidosis.

It is an inflammatory disorder of uncertain etiology, most prevalent in African-Americans from the southern United States, but sarcoidosis can present as a papulonodule or infiltrated plaque, mimicking a neoplastic disorder.

Palpation and appreciation of textural changes

Any discussion of morphology must include textural change, and palpating a lesion often provides important diagnostic clues. In dermatology, palpation can prove useful in several ways. Firstly, it helps in making a distinction amongst primary morphologies (see Table 0.1 ). For example, the key difference between macules and papules, or patches versus plaques, is that macules and patches are flush with the surrounding skin and cannot be appreciated by palpation. On the other hand, papules and plaques, by definition, must be palpable ( Table 0.3 ). Secondly, palpation may augment the examination and appreciation of a disease process for which visual changes are absent, unimpressive, or nonspecific. For example, in morphea, an autoimmune connective tissue disease that leads to sclerotic collagen within the dermis, the skin feels indurated (very firm) while only nonspecific hyperpigmentation may be evident with visual inspection. The same is true for other fibrotic disease processes, such as nephrogenic systemic fibrosis and systemic sclerosis. Likewise, atrophy, be it epidermal, dermal or subcutaneous, also serves as a diagnostic clue ( Fig. 0.5 ). Lastly, purpura is often classified as palpable or non-palpable, and this division implies different underlying etiologies (e.g. small vessel vasculitis aligned more with palpable purpura than macular purpura). Examples of useful distinctions that can be gleaned via palpation are outlined in Table 0.4 .

Table 0.3

Use of palpation in defining cutaneous lesions.

USE OF PALPATION IN DEFINING CUTANEOUS LESIONS
Types of lesion			Examples
Macules & patches (non-palpable)			• Solar lentigines • Idiopathic guttate hypomelanosis • Melasma • Vitiligo • Petechiae • Dermal melanocytosis
Papules & plaques (palpable)			• Psoriasis • Lichen planus • Dermatitis • Intradermal or compound melanocytic nevus • Hypertrophic scar, keloid • Morphea
Atrophy – dermal & subcutaneous		(A) (B) (C)	• Anetoderma • Focal dermal hypoplasia (Goltz syndrome) • Lipoatrophy due to corticosteroid injections • Lipoatrophy due to panniculitis

 

Major types of cutaneous atrophy.

Photos courtesy, Jean L Bolognia, MD.

Variation in skin color within the human population

Many racial and ethnic descriptors are used in common parlance, including African, African-American, Asian, Middle Easterner, Northern European, Southern European, Native American, Pacific Islander and Hispanic, to describe individuals with similar cutaneous characteristics as well as heritage. Yet even within racial and ethnic groups, gradations exist with regard to skin pigmentation. Sometimes the term “skin of color” is used to describe all skin tones darker than those of white (Caucasian) skin . However, this term encompasses more than skin color and its response to ultraviolet irradiation, as is assessed by the Fitzpatrick Scale (skin phototypes I–VI; Table 0.6 ). It also refers to other shared characteristics, such as hair color, hair texture, and a tendency toward certain reaction patterns in the skin as a response to an insult. The practice of dermatology requires a solid understanding of the differences in clinical features (e.g. hues of red) amongst individuals with different levels of skin pigmentation.

Variations in skin color are due to differences in the amount and distribution of melanin within epidermal melanocytes and keratinocytes , rather than the number of melanocytes (see Ch. 65 ). In addition, the ratio of eumelanin (brown–black) to pheomelanin (yellow–red) influences skin color, with pheomelanin the predominant pigment in those with freckles and red hair. Exposure to ultraviolet radiation also significantly impacts melanin production (tanning).

Pigmentation of the skin clearly influences the prevalence of certain cutaneous findings and disorders. For example, individuals with darkly pigmented skin are more likely to develop multiple streaks of longitudinal melanonychia (see Ch. 71 ) , pigmentation of the oral mucosa , persistent postinflammatory hyperpigmentation (see Ch. 67 ), and obvious pigmentary demarcation lines (Futcher lines or Voigt lines; see Fig. 67.12 ). Whether postinflammatory hypopigmentation is more common or just more clinically apparent is a matter of debate. In addition, discoid lupus erythematosus and keloids are seen more often in patients with darkly pigmented skin and African ancestry, but the relationship of these disorders to melanocyte function is not clear.

There can also be differences in the physiologic properties of the skin. For example, the stratum corneum of black skin often retains more layers and is more compact and cohesive than that of white skin. In addition, darker skin produces less vitamin D ₃ in response to equivalent amounts of sunlight, and this is postulated to have been a driving force in the evolution of paler skin as early humans migrated away from the equator .

Perhaps the most important point to remember is that erythema (redness) can be difficult to appreciate in darkly pigmented skin. Erythema is caused by vasodilation and/or increased blood flow within the dermis, and if the epidermis is deeply pigmented, the red hues of oxyhemoglobin are often less obvious. For this reason, diseases that are classically described as erythematous (e.g. cellulitis) or violaceous (e.g. lichen planus) may present more subtly in darker skin types ( Fig. 0.6 ) . Diagnostic procedures that depend upon the development of erythema, such as patch testing for the evaluation of allergic contact dermatitis, can be more challenging to interpret in dark skin. Lastly, cyanosis (blue hues indicative of poor oxygenation and a critical clinical sign) is also more difficult to appreciate when the skin is darkly pigmented.

Lichen planus presents differently in darkly pigmented versus lightly pigmented skin.

A,B The erythematous to violaceous hue seen in lightly pigmented skin is more muted in darkly pigmented skin and the lesions appear brown–black in color. Wickham striae (lacy white pattern) are more easily seen in B .

Configuration

Appreciation of the configuration or arrangement of skin lesions can provide important clues as to the diagnosis. Examples include annular (e.g. tinea corporis, granuloma annulare; see Ch. 19 ), serpiginous (e.g. cutaneous larva migrans), clustered/grouped (e.g. piloleiomyomas, herpetiform vesicles), reticulated (e.g. erythema ab igne), and retiform (e.g. purpura fulminans, purpura due to calciphylaxis [ Fig. 0.8 ]; see Ch. 22 ). The latter pattern reflects occlusion of the cutaneous vasculature .

Retiform purpura and cutaneous necrosis secondary to calciphylaxis.

Note the irregular shape of the purpura.

Courtesy, Amanda Tauscher, MD.

It also important to note if the cutaneous lesions are in a linear configuration ( Fig. 0.9 ). The lesions may follow the lines of Blaschko, which reflect patterns of embryonic development (see Fig. 62.1 ) , or they may be confined to a dermatome, which represents an area of skin whose innervation is from a single spinal nerve (see Fig. 80.14 ). Irrespective of whether the lesions are along the lines of Blaschko (e.g. epidermal nevi) or in a dermatomal pattern (e.g. herpes zoster [see Fig. 0.7 ]), there is often a characteristic midline demarcation. In addition to these two patterns, a linear arrangement can result from a trauma-induced Koebner phenomenon (an isomorphic response [ Table 0.7 ]), as in vitiligo, lichen planus ( Fig. 0.10 ), and psoriasis , or it may be due to trauma-induced autoinoculation, as in verrucae vulgares or verrucae planae. Linear lesions are frequently seen in acute allergic contact dermatitis due to plants (e.g. poison ivy), reflecting brushing of the branches and leaves against the skin. Lastly, papulonodules due to a range of infectious agents can align along lymphatic vessels in a sporotrichoid pattern (see Ch. 77 ).

Linear configuration patterns.

Some of the photographs courtesy, Jean L Bolognia, MD; Edward Cowen, MD; Louis A Fragola, Jr, MD; Joyce Rico, MD; Kathryn Schwarzenberger, MD.

Koebernization (isomorphic response) of lichen planus secondary to trauma.

As a result, the lesions have a linear configuration.

On occasion, cutaneous lesions have an unusual, even “unnatural”, shape that corresponds to an external (exogenous) insult, such as allergic or irritant contact dermatitis ( Fig. 0.11 ), an accidental or purposeful injury (see Ch. 90 ) , or even ritualistic medicinal practices (e.g. “cupping” or “coining”; see Ch. 133 ).

Allergic contact dermatitis to a para-phenylenediamine-based (“black henna”) temporary tattoo.

The shape of the lesion clearly suggests an exogenous insult/etiology.

Courtesy, Colby Evans, MD.

Distribution

Stepping back and observing the anatomic distribution pattern of skin lesions can also prove very helpful. For example, plaques of psoriasis often favor extensor surfaces (e.g. elbows and knees) while lichenified plaques of atopic dermatitis favor flexural surfaces in older children and adults (e.g. the antecubital and popliteal fossae; Table 0.8 ). However, to complicate matters a bit, there is an “inverse” form of psoriasis in which lesions are present in major body folds, i.e. in flexural areas (see Ch. 8 ). Langer cleavage lines refer to natural skin tension lines that are often used to guide the orientation of surgical excisions (see eFig. 142.3 ). The long axis of oval lesions of pityriasis rosea and erythema dyschromicum perstans follows these cleavage lines, and this pattern is most obvious on the posterior trunk.

A seborrheic distribution pattern includes the head and neck as well as the upper trunk, and it reflects areas rich in sebaceous glands; seborrheic dermatitis, acne vulgaris, and pityriasis versicolor are dermatoses that favor these sites. The term “ photodistribution ” describes lesions that are accentuated in areas exposed to ultraviolet irradiation, and photodermatoses include polymorphic light eruption, phototoxic drug reactions (e.g. to doxycycline), and subacute cutaneous lupus erythematosus. Of note, sometimes a disorder will display a combination of distribution patterns; for example, in dermatomyositis, lesions can be both photodistributed and involve extensor surfaces (e.g. elbows, knees).

In addition to differences in the color of inflammatory lesions, individuals with darkly pigmented skin also have an increased frequency of several cutaneous disorders (see section on Color ) and certain types of reaction and distribution patterns . Examples of these reaction patterns include papular eczema and a follicular accentuation of atopic dermatitis and pityriasis versicolor, as well as an annular configuration of seborrheic dermatitis and facial secondary syphilis. An example of a favored distribution pattern is inverse pityriasis rosea in which lesions occur primarily in the axillae and groin rather than on the trunk. Although a sound explanation for these phenomena is not currently available, it is still important to be aware of their occurrence .

Sometimes the distribution is best explained by the phenomenon of locus minoris resistentiae in which certain anatomic sites are more vulnerable than others to a particular disease process . Examples would be cutaneous infections within a lymphedematous limb and asteatotic eczema within a skin graft site.