Diagnosis and Examination Techniques

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[edit] Diagnosis and Examination Techniques

Frank Parker

James C. Shaw


[edit] AN APPROACH TO DIAGNOSING SKIN DISEASE

Dermatology is a visual specialty. The patient's skin condition is apparent and readily observed by the physician. Because there are hundreds of dermatoses, a logical process of elimination is needed to narrow the possibilities, first to a specific group of diseases and finally to one condition, when initially examining a patient with a skin disease. Such a diagnostic approach is based on specific morphologic description of the skin lesions along with an appropriate history and laboratory tests. This systems analysis approach to diagnosis involves three steps. First, the primary and secondary skin lesions are identified. Second the examiner places the patient in one of several major diagnostic groups of diseases. Many skin conditions are found in each of the groups, but all the diseases in a given group tend to manifest the same primary and secondary lesions. The third step involves selecting the one disease the patient has from the other conditions in the group. This step is accomplished by looking for specific features such as location and distribution of skin lesions, unusual shapes or arrangements of the lesions (annular, serpiginous, dermatomal), color, and surface characteristics (appearance of scales, verrucous or vegetative changes).

Figure 82-1 KOH examination of tinea versicolor. Note shorter nonbranching hyphae.
Figure 82-1 KOH examination of tinea versicolor. Note shorter nonbranching hyphae.


[edit] Step 1: Description of Primary and Secondary Skin Lesions

Primary skin lesions are uncomplicated lesions that represent the initial cutaneous pathologic changes uninfluenced by secondary alterations such as infection, trauma, or therapy. Secondary skin lesions are changes that occur as a result of progression of the disease, scratching, or infection of the primary lesion. At times primary changes also can occur as secondary manifestations (i.e., pustules may appear as primary lesions of folliculitis or as secondary lesions when pruritic primary lesions are scratched and infected). The challenge is to recognize a primary skin lesion as the initial change characteristic of a disease.

The terminology used to describe primary and secondary skin lesions is the basic language of dermatology, the means by which skin diseases are accurately described (Table 82-1). Each descriptive term is not only a short account of what is seen on the surface of the skin, but also implies specific information about pathologic processes within the skin.


Table 82-1 Primary and Secondary Skin Lesions

LesionDescription
Primary skin lesions 
MaculeCircumscribed change in skin color without elevation or depression of the surface, Example: erythema, purpura, café au lait, vitiligo ( Plate 1 ).
PapuleA solid elevated area no more than 10 mm in diameter. Implies pathologic involvement of epidermis (especially if there is scaling or disturbance of the normal surface of the epidermis) or dermis (usually epidermal surface is normal but redness is present). Example: warts, molluscum contagiosum, lichen planus ( Plate 2 ).
NoduleSimilar to a papule but larger (1 cm or larger in diameter) with visible elevation of the skin. It may represent a pathologic process in the epidermis, in which case it may be associated with scale, erosion, and loss of skin markings or dermis, where it may be fluctuant (if it is a cyst) or firm (if it is a skin cancer or granulomatous infiltrate). Example: cyst, basal cell carcinoma ( Plate 21 ).
PlaqueEvolves from a confluence of papules leading to a flat-topped, circumscribed elevation. Example: psoriasis, urticaria, mycosis, fungoides ( Plate 3 ).
WhealSpecial type of plaque. A slight elevation caused by movement of fluid out of blood vessels. Example: hives ( Plate 4 ).
Vesicles and bullaeCircumscribed, elevated lesion with cavities containing free fluids that flow out if the lesion is pricked. Vesicles are less than 10 mm in diameter. Bullae are greater than 1 cm in diameter. Vesicles and bullae may evolve within the epidermis ( Plates 5 and 6 ), in which case the fluid is usually clear serous. The lesions may be flaccid and easily break (i.e., very thin roof), or they may evolve at the DEJ, in which case the lesions are tense, may contain hemorrhagic fluid, and are less likely to rupture (thick roof). Umbilicated vesicles suggest viral-induced lesions (herpes simplex and zoster). Example: pemphigus, pemphigoid, porphyria cutanea tarda.
PustuleA vesicle containing purulent exudate. Example: acne, folliculitis ( Plate 7 ).
ScaleDesiccated thin plates of cornified epidermal cells that result from altered keratinization. Scale occurs when the epidermis is perturbed and involved scale assumes different appearances that can be useful in diagnosis, including, fine, thin squames seen in eczema or exfoliative dermatitis; thick, silvery scales typical of psoriasis ( Plate 8 ).
AtrophyLoss of tissue with depression of the surface of the skin. Atrophy may involve the epidermis with fine wrinkling and redness (stria) or the dermis with whitish depression (scleroderma) ( Plate 9 ).
TelangiectasisPersistent dilation of individual vessels in the skin, usually associated with alterations in the connective tissue of dermis. Example: connective tissue diseases, radiation skin damage ( Plate 7 ).
Secondary skin lesions 
LichenificationDry, leathery thickening of the skin with exaggerated skin markings. Thickening of the epidermis resulting from repeated rubbing and scratching of the skin in chronic dermatitis. Example: atopic dermatitis, neurodermatitis ( Plate 10 ).
FissuresErosion and breaks in the skin of varying depths and causes. Fissures are linear cracks in the skin, usually through the epidermis. Example: chronic eczema, perléche. Erosions are wide, shallow defects in the skin ( Plate 11 ).
UlcerDeep loss of skin into the dermis and even into the subcutaneous tissue. Example: Venous and arterial ulcers ( Plate 12 ).
ScarAn area of replacement fibrosis of the dermis or subcutaneous tissues. Scars vary in appearance and may be depressed or raised. Example: keloids may appear as nodules ( Plate 13 ).
CrustsDried exudate of serum, blood, sebum, or purulent material on the skin surface after vesicles or bullae break down to release their contents ( Plate 14 ).
OozingLoss of stratum corneum or breakdown of small vesicles with serum covering the skin surface. Example: acute dermatitis ( Plate 15 ).
DEJ, Dermal-epidermal junction.



[edit] Step 2: Assignment of Spectrum of Primary and Secondary Lesions to a Major Group of Skin Diseases

Each disease within a given group shares the same primary and secondary skin lesions. Because some diseases have overlapping traits, they may be assigned to more than one group. An arbitrary grouping of common skin diseases listed in Table 82-2 according to their dominant skin lesion is used in this section to facilitate discussion.


Table 82-2 Major Groups of Skin Diseases

Skin diseaseDominant skin lesions
Dermatitis or eczemasErythema papules, vesicles, lichenification, oozing, crusts
 Example: contact dermatitis, atopic eczema, nummular eczema, stasis eczema
Papulosquamous skin diseasesUnique papules, plaques, and scales
 Example: psoriasis, pityriasis rosea, lichen planus
Pustular skin diseasesPapules and pustules
 Example: acne, rosacea, folliculitis
Nodular skin diseasesEpidermal and dermalnodules
 Example: benign skin tumors and malignant skin tumors
Vesiculobullous skin diseasesVesicles and bullae
 Example: infectious—impetigo, herpes; immunologic—pemphigus and pemphigoid; mechanical—epidermolysis bullosa.
Pigmentary alterations of the skinHyperpigmented and hypopigmented macules
 Example: vitiligo, Addison's disease, albinism, melasma
Maculopapular eruptionsMacules and papules
 Example: childhood exanthems, drug eruptions, purpuric lesions
Special erythematous reactions of the skinMacules and plaques
 Example: urticaria, dermatographism, insect bites
Ulcerative skin lesionsExample: pyoderma gangrenosum, ulcers due to vascular diseases, infectious ulcers



[edit] Step 3: Narrowing the Possibilities within a Given Group to the Exact Diagnosis

Several factors are important in identifying the specific skin condition within each group. The distribution of the skin lesions is important because many conditions have typical patterns or often affect specific regions. For example, psoriasis commonly affects extensor surfaces and atopic eczema involves flexor areas of extremities. Photoreactions are confined to the sun-exposed areas of the body. Involvement of the palms and soles is seen in erythema multiforme, secondary syphilis, psoriasis, and eczema. Contact dermatitis presents with unusual patterns corresponding to areas where the offending material contacts the skin.

A second important clue in differentiating diseases within a given group is the shape of individual lesions and the arrangement of lesions in relation to one another. For example the lesions of lichen planus characteristically are angular papules, whereas pityriasis rosea presents as oval, raised patches. A linear arrangement of lesions is typical of contact with an exogenous substance brushing across the skin or a cutaneous nevus. “Zosteriform” refers to lesions arranged along the cutaneous distribution of a spinal nerve in a bandlike, unilateral configuration (e.g., herpes zoster, dermatomal hemangiomas in Sturge-Weber syndrome) ( Plate 16 ). Annular lesions are circular with normal skin in the center. Annular macules are observed in drug eruptions, secondary syphilis, and lupus erythematosus. Scaling annular lesions suggest dermatophytosis ( Plate 17 ). Iris lesions are a special annular lesion in which a papule or vesicle evolves into the center-target or bullseye lesion typical of erythema multiforme ( Plate 18 ). Urticaria polycyclic patterns evolve when numerous annular lesions enlarge and run together (hives). Serpiginous (snakelike patterns) are seen in creeping eruption ( Plate 19 ). Herpetiform refers to the grouping of lesions seen in herpes simplex or dermatitis herpetiformis ( Plate 5 ).

Other physical features are important in diagnosing skin diseases. Dry, lichenified lesions ( Plate 10 ) suggest a chronic state of a disease, whereas wet, oozing, macerated lesions ( Plate 15 ) suggest acute reactions. Nodular lesions that are soft, fluctuant, and tender suggest an abscess, whereas firm nodules are likely to be a benign or malignant tumor ( Plate 1 ). Redness caused by dilation of superficial blood vessels blanches with pressure, whereas erythema caused by extravasated blood, as occurs in petechiae and purpura, does not blanch ( Plate 20 ). Hues of blue and black indicate melanin pigment. The deeper the melanin pigmentation deposition in the skin, the bluer the color ( Plate 21 ).


[edit] Dermatologic History

Although the clinical examination is vital in diagnosing skin disease, the history is also important and certain specific information should be determined if possible:

  • Onset: Where precisely on the body did the condition begin? What did it look like? What are associated symptoms?
  • Course: How did the disease progress and change? What has been done to treat the condition (by the patient or by physicians)? What is the relationship to vacations, seasons, the environment? Has the condition been continuous or intermittent?
  • Past Medical History: Does the patient have other cutaneous diseases? Is there a history of atopy, endocrine conditions, skin, or other malignancies or autoimmune diseases?
  • Family History: Is there a history of atopic diseases and allergies, psoriasis, or other inherited conditions in family members?
  • Work and Hobbies: What work or hobbies of the patient may expose them to contactants?
  • Topical and Systemic Medications and Materials Used: Because drug reactions are so common (both to topical and systemic medications—prescribed and over the counter), the physician should always be alert to this possibility. What medications does the patient apply,especially with rubber gloves? Does the patient use topical steroids? Are other cosmetics, anti-itch products, and other topical medications used? What medications are used in every orifice (i.e., eyedrops, eardrops, suppositories, oral). Even vitamins, cough medications, and birth control pills may cause skin reactions.

The chapters in this section deal with the major disease groups (e.g., dermatitis, papulosquamous, pustular). Not every skin group listed in Table 82-2 is identified as a separate chapter; some chapters are listed based on etiologic factors (e.g., infectious diseases of the skin, common reaction patterns [hives, erythema multiforme], and photoreaction). Nevertheless, it should be possible for the physician to “place” a patient presenting with a common skin condition into the appropriate chapter and further to arrive at a precise diagnosis if the steps in the preceding systematic clinical approach are followed.In this section, skin conditions are discussed in association with internal diseases and in pediatric, geriatric, and black patients. Finally, a chapter on the general principles of dermatologic therapy is included to help the clinicians treat the common disorders.


[edit] EXAMINATION TECHNIQUES

The examination of the skin by inspection is the most valuable step in dermatologic diagnosis. The use of selected tests can be helpful in confirming or excluding suspected diagnoses. These include the potassium hydroxide (KOH) examination, Gram's stain, Tzanck smear, selected cultures, and skin biopsy for histologic examination. An understanding of when and how to perform these ancillary tests is essential in dermatologic diagnosis (Table 82-3).


Table 82-3 Ancillary Tests in Dermatology: When to Use Them

TestIndicationsPrecautions
KOH (potassium hydroxide)Fungal infections of skin or mucosaLarge depth of field on microscope. Never need greater than 40× lens
 Tinea versicolor: short, plump hyphae and spores (see Fig. 82-1).Debris can look like fungal hyphae
 Scabies: look for a linear burrow.Scabies: scan at low power (2× or 4×)
 Any red, scaly dermatosis where diagnosis uncertain 
Gram's stainBacterial folliculitis (gram-positive cocci in clumps)Federal regulations may not allow this test as an office procedure.
 Pustular eruption (sterile if psoriasis, drug reaction) 
 Candida, when there are pustules (gram positive) 
Tzanck smearTo confirm or rule out herpesvirus infection:Frequently much cellular debris: PMNS, lymphocytes
  HSV 
  herpes zoster 
  varicella 
 Confirms molluscum bodies in material from molluscum lesions. 
Direct if for herpesvirus infectionConfirmation of herpesvirusRequires special glass slides from laboratory.
 Identifies HSV 1 and 2 and varicella-zoster virus 
CulturesBacterial infectionsNegative result does not exclude infection.
 Nasal staphylococcal carrier statePositive bacterial culture may not be the primary cause of the disease (i.e., leg ulcers, mouth ulcers, crusted lesions)
 Fungal disease: nail, scalp 
 HSV: positive in 48-72 hours 
 CMV infection 
Wood's light examinationFungal infections (tinea capitis from Microsporum species fluoresces green)Not confirmatory
  Negative test does not rule out disease.
 Inguinal dermatitis (erythrasma fluoresces coral red) 
Skin biopsyAny atypical dermatosis where a specific diagnosis will influence treatment.Consultation by dermatologist may be more cost effective if no biopsy required.
 If malignancy is in the differential diagnosisMany dermatoses do not have pathognomonic histologic findings.
 If histologic confirmation is desirable by patient, epidemiologists, treating physicians 
  Sampling errors may hinder making a correct diagnosis.
 Atypical presentations of common disordersPathology report without diagnostic possibilities (i.e., descriptive only) may not help in making the diagnosis.
 Skin lesions in immunocompromised patients 
HSV, Herpes simples virus; PMNS, polymorphonucleocytes; CMV, cytomegalovirus.



[edit] Examination of the Skin
[edit] Morphology.

Color, size, shape, texture, as well as the presence or absence of scale, serum crust, or pus, are a few important morphologic features of primary lesions that aid in making a correct diagnosis and communicating with dermatologists. Good lighting and magnification are important, and examination of the entire skin surface is frequently required.


[edit] Distribution.

Certain diseases have characteristic distributions that are pathognomonic even if the primary lesions are not characteristic (i.e., herpes zoster in a dermatomal distribution and photo-related skin eruptions on sun-exposed areas: central face, extensor arms, and dorsal hands).


[edit] Palpation.

While macules feel like normal skin, palpable lesions may reflect epidermal, dermal, or subcutaneous involvement. A rough surface or scaling suggests epidermal involvement; a smoother surface usually implies dermal or deeper involvement.


[edit] KOH Examination

KOH examination ( Plates 22 and 23 ) of skin rapidly confirms or excludes tineas (dermatophyte fungi), candidiasis, scabies, or tinea versicolor (Fig. 82-1). The KOH examination helps dissolve keratin and allows for separation of aggregates of stratum corneum cells but does not disrupt the cell walls of fungi. All of the following steps must be optimal for a successful test:

  • Obtain copious scale with a no. 15 blade onto a glass slide. In annular lesions, scrape the peripheral scale. Center material on slide and place cover slip.
  • Apply KOH (10% to 20%). DMSO 5% helps with penetration of the KOH.✢✢Solution can be obtained from DELASCO, 800-831-6273.
  • Heat the slide, with gentle agitation. Blot excess fluid.
  • The microscope must have the appropriate optical settings. The ten power (10×) objective is the best to look for fungal hyphae. The four power (4×) is best for the larger scabies mites. In both cases, the visualization is optimal with a large depth of field made by closing down the iris or bylowering the condenser lens. The forty power (40×) lens can be used to confirm findings but should not be used to search for fungi. The oil immersion (100×) lens is not necessary in the KOH examination and can actually hinder the chances of finding hyphae.


[edit] Gram's Stain

Once utilized and valued as a diagnostic test by physicians, recent federal regulations allow only certified laboratories to perform Gram's stains. Most specimens sent for culture will include a Gram's stain.


[edit] Tzanck Smear

The Tzanck smear is the most rapid way to identify herpesvirus infection, including herpes simplex virus (HSV), varicella, and herpes zoster. Any dark nuclear stain is acceptable. A 5% methylene blue solution is inexpensive and effective, but Wright's or Geimsa stain also work well.


[edit] Preparation.

Open a vesicle and scrape the base or the under side of the blister roof. Smear onto a slide, air dry, and fix with absolute alcohol or gentle heating. Stain with Geimsa or Wright's for 1 minute or methylene blue for 15 seconds. Rinse, dry, and examine at 10× and 40× power. Immersion oil and a cover slip optimize the optics.


[edit] Interpretation.

Look for multinucleated keratinocytes ( Plate 24 ). The keratinocytes become “fused” in herpesvirus infections and appear as large cells with multiple nuclei. Neutrophils and mononuclear cells frequently are also present on a Tzanck smear and are much smaller than the multinuclear keratinocytes.


[edit] Direct Immunofluorescence for Herpesvirus

Direct immunofluorescence (IF) is now available in most laboratories and is valuable in rapidly confirming the presence of HSV 1 or 2 or varicella-zoster virus. Obtain material as for a Tzanck smear and place in wells on special slides from the lab. Results are usually available within 2 hours.


[edit] Cultures

Fungal culture is most valuable in cases of tinea capitis and nail infections, both of which are difficult to diagnose by inspection and KOH examination. In tinea capitis, use either plucked hairs or swab/brush and place directly into media provided by the laboratory. Bacterial culture can be helpful in any atypical pustular eruption. Culture of the anterior nares is useful to diagnose a staphylococcal carrier state. HSV usually grows in 48 hours; varicella-zoster virus requires up to 4 weeks to grow and is frequently negative. Tissue cultures from biopsy specimens are indicated when deep fungi, atypical mycobacteria, or other deep bacterial involvement are suspected.


[edit] Wood's Light Examination

The use of a Wood's light (ultraviolet light, 360 nm) helps diagnose certain fungal and bacterial infections and helps delineate some disorders of pigmentation. Most tinea capitis does not fluoresce, since Tinea tonsurans became the predominant organism. Erythrasma, the intertriginous infection with Corynebacterium minutissimum, can fluoresce a coral-red color if the water soluble porphyrins have not been recently washed off.


[edit] Skin Biopsy

The punch biopsy is the most common form of skin biopsy, with punches ranging in size from 2 mm to 8 mm in diameter. Most skin diseases are best sampled by this method because the epidermis, dermis, and subcutaneous fat are present in one sample. If the skin lesion is raised above the skin surface, a shave biopsy of superficial skin can be used, and in cases where deep tissue or a larger sample are needed, an incisional or excisional biopsy is indicated.


[edit] Indications.

There are no absolute indications for doing a skin biopsy. This is because there are frequently nonspecific histologic findings that do not allow confirmation of a particular diagnosis, and because management of the patient may not be affected by a histologic diagnosis. In cases where consultation by a dermatologist may obviate the need for biopsy, considerations pertaining to cost effectiveness may be important. In spite of these uncertainties, some general principles apply when considering performing a skin biopsy (see Table 82-3).


[edit] Procedure.

In most cases the required materials include local anesthetic, a biopsy punch or scalpel, and means of achieving hemostasis. Healing is rapid after closure with sutures but usually is adequate when the wound is allowed to heal by granulation. Hemostatic products include aluminum chloride, silver nitrate, and Gelfoam packing.


[edit] Interpretation.

Dermatopathology is a subspecialty of its own because of the complexity of skin pathology. A skin biopsy in the primary care setting may not always provide an answer to a dermatologic problem. The following factors determine the quality of the information from a biopsy:

  • Characteristic pathologic findings: Many skin diseases have nonspecific histologic changes, and skin biopsies may be noncontributory (e.g., atopic dermatitis, urticaria, drug eruptions, viral exanthems).
  • Sample location: A biopsy from the center of a lesion has the best chance of demonstrating pathology. Occasionally, a sample from the periphery of the lesion shows the characteristic changes (e.g., some bullous diseases).
  • Sample size or depth: A sample that is not large enough or deep enough may not demonstrate the pathologic changes.
  • The pathologist: The person who interprets the skin biopsy must be an expert in the histopathology of the skin. Dermatopathologists are the best trained in this field, although general pathologists and dermatologists receive training in skin pathology.

Ideally, a pathology report either confirms a specific diagnosis, or discusses differential diagnoses and suggests further diagnostic procedures if indicated.


[edit] ADDITIONAL READINGS

  • TP Habif: Clinical dermatology ed 3. St Louis: Mosby; 1996:
  • JK Robinson, PE LeBoit: Biopsy techniques: description and proper use. Arndt KAet al.: Cutaneous medicine and surgery. Philadelphia: Saunders; 1996:
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