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a rash🚧 施工中
a rash
Sarah Stein, MD
CHIEF COMPLAINT
PATIENT
Ms. N is a 23-year-old woman who comes to see you complaining of a rash.
What is the differential diagnosis of a rash? How would you frame the differential?
CONSTRUCTING A DIFFERENTIAL DIAGNOSIS
In clinical practice, rashes are diagnosed through pattern recognition (sometimes called system 1 reasoning) probably more than any other complaint. This is an effective way of making a diagnosis when the diagnosis is obvious or when the observer is very experienced. The risk with this type of reasoning is that diagnostic hypotheses are heavily influenced by recent experience, rare diagnoses tend not to be recognized, and physicians often reach premature closure on an incorrect diagnosis.
The differential diagnosis of a rash should be based on the morphology of the lesion. This can be considered the first pivotal point in the differential diagnosis. To correctly categorize a lesion’s morphology, the physician must first identify the primary lesion, the typical element of the eruption. This process can be complicated as the primary lesion is often affected by secondary changes such as excoriation, erosion, crusting, or coalescence. Because the differential diagnosis of 1 lesion can be extensive, once the morphology of the primary lesion is identified, the next pivotal points are determining the global reaction pattern and observing the distribution of lesions. What follows are some important definitions, followed by a differential diagnosis of some of the most common reaction patterns.
1. Macule: lesion without elevation or depression, < 1 cm
2. Patch: lesion without elevation or depression, > 1 cm
3. Papule: any solid, elevated “bump” < 1 cm
4. Plaque: raised plateau-like lesion of variable size, often a confluence of papules
5. Nodule: solid lesion with palpable elevation, 1–5 cm
6. Tumor: solid growth, > 5 cm
7. Cyst: encapsulated lesion, filled with soft material
8. Vesicle: elevated, fluid-filled blister, < 1 cm
9. Bulla: elevated, fluid-filled blister, > 1 cm
10. Pustule: elevated, pus-filled blister, any size
11. Wheal: inflamed papule or plaque formed by transient and superficial local edema
12. Comedone: a plug of keratinous material and skin oils retained in a follicle; open comedone has a black inclusion, closed comedone appears flesh-colored or pinkish
Primary lesions are further grouped into reaction patterns. Papulosquamous eruptions present with papules and plaques associated with superficial scaling. Folliculopapular eruptions begin as papules arising in a perifollicular distribution. Dermal reaction patterns result from infiltrative and inflammatory processes involving the dermal and subcutaneous tissues. Petechia and purpura occur when there is leakage of blood products into surrounding tissues from inflamed or damaged blood vessels. Blistering disorders present with vesicles and bullae. A differential diagnosis of rash is listed below and Figure 29-1 presents an algorithm of a possible approach to patients with rashes and skin lesions.
Figure 29-1. Approach to the patient with rash or skin lesion.
A. Blistering disorders (vesicles, pustules, and bullae)
1. Autoimmune
a. Bullous pemphigoid
b. Epidermolysis bullosa acquisita
c. Pemphigus vulgaris
2. Hypersensitivity syndromes
a. Stevens-Johnson syndrome
b. Toxic epidermal necrolysis
3. Infectious
a. Herpes simplex
b. Impetigo
c. Staphylococcal scalded skin
d. Varicella zoster
B. Dermal reaction patterns
1. Erythema nodosum
2. Granuloma annulare
3. Sarcoidosis
4. Urticaria
C. Folliculopapular eruptions (perifollicular papules)
1. Acne vulgaris
2. Folliculitis
3. Perioral dermatitis
4. Rosacea
D. Papulosquamous eruptions (papules and plaques with scale)
1. Eczematous dermatitis
a. Allergic contact dermatitis
b. Atopic dermatitis
c. Irritant contact dermatitis
2. Pityriasis rosea
3. Psoriasis
4. Seborrheic dermatitis
5. Tinea infections
E. Purpura and petechiae
1. Nonpalpable purpura
a. Actinic/senile purpura
b. Amyloidosis
c. Bacteremia
d. Benign pigmented purpura
e. Corticosteroid-associated
f. Disseminated intravascular coagulation
g. Medication-related
h. Thrombocytopenia
2. Palpable purpura
a. Infectious
(1) Bacteremia
(2) Rocky Mountain spotted fever
(3) Meningococcemia
b. Leukocytoclastic vasculitis
(1) Allergic vasculitis
(2) Henoch-Schönlein purpura
Ms. N complains of frequent “breakouts” on her face for the last several years. She reports the use of many topical over-the-counter agents over the years. She complains of feeling greasy and the need to “squeeze pus” out of lesions on a regular basis.
On examination, there are many erythematous papules, occasional pustules, and open and closed comedones on the forehead, cheeks, and chin. There is a predominance of larger nodules along the jaw line. Similar erythematous papules involve the upper back and chest. There is neither significant background erythema nor scaling in the scalp, eyebrows, or nasolabial folds. Figure 29-2 shows her on her initial visit.
At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?
Figure 29-2. Ms. N on initial presentation.
RANKING THE DIFFERENTIAL DIAGNOSIS
The pivotal clues, in this case, are the morphology of the lesion and its distribution. This patient has a folliculopapular eruption that predominantly affects the face, chest, and upper back. Primary lesions of inflammatory papules, pustules, and comedones place acne at the top of the differential. The history is typical for acne: a chronic course with intermittent flares.
Other folliculopapular conditions must be considered. The lack of background erythema and telangiectasias makes a diagnosis of rosacea less likely. Perioral dermatitis typically presents as monomorphic small papules and is closely associated with the use of topical corticosteroids and cosmetics. The mixture of lesion type, with comedones as well as papules and nodules, and the more diffuse distribution makes acne more likely than perioral dermatitis. An infectious folliculitis is possible, but the course of the disease makes this extremely unlikely (Table 29-1).
Table 29-1. Diagnostic hypotheses for Ms. N.
The patient is in good health and is not overweight. She is not taking any oral medications. She reports regular menstrual cycles and notes that the breakouts are worse around the time of her period. She does not report easy flushing or any increased hair growth on the face or chest. She has 1 healthy child.
Is the clinical information sufficient to make a diagnosis? If not, what other information do you need?
Leading Hypothesis: Acne Vulgaris
Textbook Presentation
Typically, acne vulgaris presents in adolescence with chronic, waxing and waning lesions. A variety of lesions are present, including inflammatory papules, pustules, comedones, and nodulocysts over the face, chest, and back.
Disease Highlights
A. Description of lesion: inflammatory papules, pustules, comedones, and nodulocysts over the face, chest, and back (see Figure 29-2).
B. Acne is a highly prevalent condition, most common during mid-to-late adolescence.
C. Acne may persist beyond adolescence, especially in women.
D. Acne is caused by the obstruction of sebaceous follicles on the face and trunk. Three factors are involved in the development of the lesions:
1. Increased sebum is produced (androgen dependent) and accumulates in follicles.
2. Desquamation of epithelial cells and keratin into sebum-rich follicles causes obstruction.
3. Inflammation develops as the anaerobe Propionibacterium acnes proliferates in this closed environment.
E. Although the 3 factors discussed above are responsible for most cases of acne, it is important to keep in mind other factors that may contribute to the disease.
1. Hyperandrogen states (most commonly polycystic ovary syndrome [PCOS] or androgenic progestins in contraceptives).
2. Exposure to topical comedogens (cocoa butter, mineral oil, lanolin, fatty acids).
3. Numerous factors that lead to follicular obstruction (eg, habits or clothing that cause skin trauma or obstruct pores, hot humid environments or heavy sweating leading to keratin over-hydration).
4. Medications known to trigger or exacerbate acne (eg, corticosteroids, isoniazid, lithium, androgens).
Evidence-Based Diagnosis
A. The diagnosis is typically clinical.
B. Work-up for hyperandrogenism is appropriate when there are signs of polycystic ovary disease, virilization, or an atypical presentation (such as later in life).
Treatment
A. Identify and remedy the acne precipitants discussed above.
B. Review general skin care techniques for acne-prone skin.
1. Vigorous scrubbing can aggravate acne by promoting the development of inflammatory lesions.
2. Abrasive cleaners and mechanical devices also aggravate acne by promoting inflammation.
3. Use of one’s hands and a mild cleanser with lukewarm water is best.
4. Use of moisturizers should be minimized and all cosmetics and lotions should be oil-free.
5. Minimize contact of facial skin with hair gels and other styling products (pomade acne).
C. Medical therapy is aimed at the 3 factors involved in acne development.
1. Decreasing sebum production
a. No topical therapies are effective
b. Estrogen
(1) Most effective at doses of > 50 mcg of ethinyl estradiol
(2) Common oral contraceptive pills containing ≤ 35 mcg ethinyl estradiol are still helpful.
c. Antiandrogens (spironolactone)
d. Isotretinoin (see later discussion)
2. Alteration of epithelial turnover and cohesiveness
a. Topical retinoids: tretinoin, tazarotene
b. Adapalene: a naphthoic acid with retinoid activity
3. P acnes proliferation and accompanying inflammation
a. Topical antibiotics
(1) Erythromycin
(2) Clindamycin
(3) Metronidazole
(4) Benzoyl peroxide
b. Systemic antibiotics
(1) Tetracycline class
(2) Macrolide class
(3) Trimethoprim/sulfamethoxazole
D. Guidelines for the use of these medications are as follows:
1. Predominantly comedonal acne: retinoid or adapalene
2. Mild inflammatory acne: topical antibiotic and benzoyl peroxide with or without retinoid or adapalene
3. Moderate to severe but noncystic inflammatory acne: systemic antibiotic in combination with a topical retinoid
4. Nodular cystic acne: isotretinoin
a. Should only be prescribed by clinicians experienced in its use because of potential adverse effects
b. Has the potential to cause hypertriglyceridemia and depression
c. Effective contraception must be assured because it is a potent teratogen.
E. Additional considerations
1. Oral contraceptives are useful in women with a strong hormonal component.
2. Spironolactone can be useful in adult women with recalcitrant acne.
MAKING A DIAGNOSIS
A clinical diagnosis of acne is most likely. Although PCOS might be considered based on the older age of the patient and the distribution of lesions along the jaw line, the patient lacks the oligomenorrhea that, along with evidence of hyperandrogenism, is necessary for making the diagnosis.
A clinical diagnosis of acne is made, and discussion about the most appropriate therapy begins.
Have you crossed a diagnostic threshold for the leading hypothesis acne vulgaris? Have you ruled out the active alternatives? Do other tests need to be done to exclude the alternative diagnoses?
Alternative Diagnosis: Rosacea
Textbook Presentation
Commonly presents in adults with a facial rash. There is a gradual development of telangiectasias and persistent centrofacial erythema occasionally with inflammatory red papules and papulopustules. Comedones are absent. There is often a history of easy flushing. The rash may worsen with sun exposure, ingestion of spicy foods and thermally hot foods/liquids, emotional stress, and exercise.
Disease Highlights
A. Description of lesion: centrofacial persistent facial erythema, telangiectasias, and, occasionally, inflammatory papules and papulopustules (Figure 29-3).
Figure 29-3. Rosacea. (Used with permission from Dr. Anne E. Laumann.)
B. Rosacea is most common in fair-skinned individuals of northern European descent but can be seen in people with darker skin as well.
C. Women are more commonly affected than men.
D. However, complicated disease with sebaceous gland hyperplasia and rhinophyma (sebaceous overgrowth causing deformity of the nose) develops more often in men.
E. Rosacea typically begins later than acne and reaches a peak in middle age. That said, the 2 can overlap.
F. Sun exposure is thought to be a trigger and sun-damaged skin is frequently seen in patients with rosacea.
G. Ocular rosacea is common, perhaps affecting more than half of patients with rosacea, and includes conjunctival hyperemia, anterior blepharitis, and keratitis.
Evidence-Based Diagnosis
A. Diagnosis is by clinical presentation.
B. Histopathology, which is rarely necessary, varies according to the stage and variant of the disease and is often nonspecific.
Treatment
A. Sun protection
B. Avoidance of triggers of flushing
1. Sun exposure
2. Ingestion of spicy and thermally hot foods and liquids
3. Emotional stressors
4. Physical exertion: encourage frequent cool-downs
C. Topical agents
1. Metronidazole (treats papules and papulopustules, modest effect on erythema)
2. Brimonidine (treats erythema)
3. Ivermectin (treats papules and papulopustules)
D. Systemic agents: oral antibiotics of the tetracycline class control severe eruptions of inflammatory lesions.
E. Laser treatment
1. Used to ablate telangiectasias and improve background erythema.
2. May be helpful to reduce rhinophyma.
CASE RESOLUTION
A management plan was discussed with the patient that included instruction on an appropriate skin care regimen, direction regarding appropriate selection of topical products, and use of systemic and topical medications. At follow-up in 3 months, the patient had significantly fewer active lesions with evidence of dyspigmentation associated with resolving lesions.
CHIEF COMPLAINT
PATIENT
Mr. B is an 18-year-old man who was in good health until 1 week ago, when he noted that the left side of his chest was painful. One day before his visit, he noticed a rash on the left side of his chest, just lateral to his sternum. He describes the rash as small bumps, blisters, and red patches. He says that the skin is extremely sensitive to light touch. He otherwise feels well, without fever or constitutional symptoms.
At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?
RANKING THE DIFFERENTIAL DIAGNOSIS
Several general etiologic categories need to be considered when presented with a patient with new-onset blisters or vesicles. Blisters can be a symptom of infection, autoimmune disease, or a reaction to an external stimulus. Infectious causes include varicella zoster virus (VZV), presenting either as chickenpox or herpes zoster (shingles), and bullous impetigo. Both are possible in this patient. The prodromal pain and unilateral, dermatomal distribution suggest VZV. Bullous impetigo can cause blisters in a young, healthy person, but these blisters often begin in intertriginous areas. Bullous impetigo is most common in children. Grouped blisters suggest VZV or herpes simplex virus (HSV), whereas other blistering diseases may demonstrate large distinct blisters or erosions.
Bullous arthropod bites can affect patients of any age. A history of exposure should be elicited. The numerous, small, clustered lesions, in this case, make arthropod bites a less likely diagnosis. Bullous pemphigoid and other autoimmune blistering disorders are rare but possible. Stevens-Johnson syndrome is unlikely given the subacute onset but is certainly a “must not miss” diagnosis (Table 29-2).
Table 29-2. Diagnostic hypotheses for Mr. B.
The patient reports no significant medical history. He recently finished a course of amoxicillin for pharyngitis. He also frequently helps his mother with gardening. The patient is afebrile with normal vital signs. The physical exam demonstrates clusters of small vesicles, filled with clear fluid, overlying erythematous skin. There is no lymphadenopathy. The rest of the skin exam is unremarkable (Figure 29-4).
Is the clinical information sufficient to make a diagnosis? If not, what other information do you need?
Figure 29-4. Mr. B. on initial presentation.
Leading Hypothesis: VZV (Herpes Zoster/Shingles)
Textbook Presentation
This condition usually presents as a rash over a single, unilateral dermatome. The lesions begin as closely grouped vesicles on an erythematous base. Over 2–3 days, the lesions become pustular and then crust over after 7–10 days. Pain and paresthesias along the involved dermatome often precede the rash by a few days.
Disease Highlights
A. Description of the lesion: small, tightly grouped vesicles on an erythematous base occurring in one dermatome (see Figure 29-4). Very early in the presentation, the lesions are large papules that then become vesicular, then pustular, and ultimately crusted.
B. Characteristics of the lesion
1. The rash tends to occur in the region where the rash of primary VZV infection (chickenpox) was most severe.
a. The most common dermatomes are trigeminal and T3–L2.
b. It is not uncommon to have a few vesicles in contiguous dermatomes.
2. New lesions may appear for several days, occasionally for up to 7 days.
C. Shingles is caused by reactivation of VZV in a dorsal root ganglion.
D. Complications
1. Herpes zoster ophthalmicus
a. Can occur when there is involvement of the first division of the trigeminal nerve.
b. The tip of the nose is in this division so vesicles in this area should raise the possibility of herpes zoster ophthalmicus.
c. Carries high risk of corneal damage
2. Herpes zoster oticus (Ramsay Hunt syndrome)
a. Reactivation of VZV within the geniculate ganglion
b. May cause facial paralysis (Bell palsy) and ear pain
c. Vesicles can often be seen in the ear canal.
d. Vestibular and hearing disturbances (vertigo and hearing loss or tinnitus) are frequently reported.
E. Disseminated varicella zoster may occur, most often in immunocompromised patients.
F. Varicella zoster in the elderly
1. Zoster can be associated with significant morbidity in elderly patients.
2. The rash is more severe and generally lasts longer in the elderly.
3. Postherpetic neuralgia, a potentially debilitating, long-term pain syndrome, is also most common in the elderly.
Evidence-Based Diagnosis
A. The diagnosis of varicella zoster is usually made clinically without additional tests.
B. Viral polymerase chain reaction (PCR) done of the vesicle fluid is useful if the diagnosis is in doubt.
C. The bedside Tzanck smear of material scraped from a fresh vesicle can be supportive evidence but cannot distinguish between VZV and HSV.
Treatment
A. In the immunocompetent, the eruption is self-limited; supportive care with pain relievers may be all that is necessary.
B. Patients with any involvement of the eye should be evaluated by an ophthalmologist.
C. Antiviral agents (acyclovir, famciclovir, valacyclovir)
1. Most useful when the rash is diagnosed within the first 72 hours
2. Decrease the duration and severity of the disease (including decreasing duration and severity of acute neuropathic pain)
3. Prevent dissemination
The use of antiviral drugs is not beneficial if the rash of varicella zoster has been present for more than 72 hours.
D. Symptomatic care: soaks and topical antipruritics might be useful.
E. Corticosteroids
1. Systemic corticosteroids have been used in conjunction with antiviral agents to reduce the duration of the rash and the acute pain syndrome.
2. Meta-analysis showed that systemic corticosteroids are probably ineffective in the prevention of postherpetic neuralgia.
F. Infection control
1. The vesicle fluid is infectious to individuals who are not immune (neither had chickenpox nor been vaccinated).
2. Infection risk can, therefore, be reduced by preventing direct contact with the vesicle fluid.
G. Postherpetic neuralgia
1. Most commonly complicates disease in the elderly
2. Potentially severe neuropathic pain syndrome
3. Meta-analyses show that systemic corticosteroids, antivirals, and other supplemental systemic therapies (gabapentin, pregabalin, amitriptyline) are ineffective in the prevention of postherpetic neuralgia, while supplemental interventional procedures (nerve block, epidural analgesics, transcutaneous electric nerve stimulation) may be beneficial.
H. Prevention
1. An inactivated recombinant vaccine was approved for use in the United States in 2017.
2. This vaccine has an efficacy of 97.2% in patients over age 50.
3. It is also effective in older patients (efficacy 90% for 70–79 years of age and 89.1% for 80 years of age or older).
4. The vaccine is recommended for patients over the age of 50.
a. Patients should receive the vaccine regardless of whether there is a history of chickenpox.
b. The vaccine should also be given 6–12 months after an episode of varicella zoster.
MAKING A DIAGNOSIS
Given the patient’s prodromal symptoms and classic dermatomal distribution, varicella zoster is the leading diagnosis. Because the rash was thought to be somewhat atypical, a fresh vesicle was unroofed with a scalpel tip and the vesicle fluid was sent for PCR testing.
The diagnosis of varicella zoster is often clinical. The distribution and clinical appearance of lesions, as well as the associated prodromal symptoms, can make the diagnosis obvious. Impetigo, bullous arthropod bites, and autoimmune blistering diseases typically demonstrate larger distinct blisters or erosions. Stevens-Johnson syndrome and other drug reactions must always be considered when medications are in use. This patient was taking amoxicillin. The clinical appearance of the lesions, their localized distribution, and the overall time course of the symptoms are not consistent with this eruption, so varicella zoster must still lead the list.
Have you crossed a diagnostic threshold for the leading hypothesis varicella zoster? Have you ruled out the active alternatives? Do other tests need to be done to exclude the alternative diagnoses?
Alternative Diagnosis: Bullous Impetigo
Textbook Presentation
Most commonly seen in children, bullous impetigo presents as flaccid, transparent bullae in the intertriginous areas. The blisters rupture easily and leave a rim of scale and shallow moist erosion.
Disease Highlights
A. Description of the lesion: flaccid bullae on normal skin (Figure 29-5)
Figure 29-5. Bullous impetigo.
B. Location of the lesion
1. Develops on grossly intact skin as a result of local toxin production.
2. This is in contrast to nonbullous impetigo, shown in Figure 29-6, resulting from Staphylococcus or Streptococcus infection, which tends to affect previously traumatized skin.
Figure 29-6. Impetigo.
3. Lesions most commonly develop on moist, intertriginous skin.
C. Superficial skin infection that most commonly affects infants and young children
D. The causative agent is Staphylococcus aureus.
E. The blistering is caused by the production of exfoliatin or epidermolytic toxins.
Evidence-Based Diagnosis
A. Diagnosis is by clinical presentation.
B. Culture of blister fluid or the moist edge of a crusted plaque may be diagnostic.
Treatment
A. Oral antibiotics active against S aureus should be prescribed for bullous impetigo. The possibility of methicillin-resistant S aureus (MRSA) must be considered.
B. Localized, nonbullous impetigo may be adequately treated with topical antibiotics (effective against gram-positive cocci) such as:
1. Bacitracin
2. Polymyxin
3. Mupirocin
C. Recurrent infections may indicate staphylococcal carriage. Eradication measures including daily washing with chlorhexidine gluconate, intranasal mupirocin ointment, and oral rifampin and doxycycline have been modestly successful.
D. Family members and close contacts may also be colonized and warrant investigation and treatment when appropriate. Environmental sources such as shared towels and athletic equipment should be considered.
Alternative Diagnosis: Bullous Arthropod Bites
Textbook Presentation
This condition commonly presents as a cluster of tense blisters on exposed skin. The blisters tend to be large (≥ 1 cm) and surrounding skin is normal.
Disease Highlights
A. Description of the lesion: large, often tense blisters on normal skin (Figure 29-7).
Figure 29-7. Bullous arthropod bites.
B. Character and location of the lesion
1. The lesions tend to develop in exposed areas of the skin, such as the extremities.
2. The patient will otherwise appear well.
3. The lesions are typically extraordinarily pruritic.
4. Although the blisters arise from otherwise normal skin, surrounding inflammatory changes from rubbing and scratching are often present.
C. Arthropod bite reactions are dermal hypersensitivity reactions to antigens from the saliva of insects.
D. Bedbugs, fleas, mosquitos and many varieties of mites are all typical culprits.
E. It is not possible to identify the culprit insect by the appearance of the bite.
Evidence-Based Diagnosis
A. Diagnosis is made by clinical presentation.
B. Histopathology, though rarely necessary, can be supportive, demonstrating edema, a subepidermal blister, and a dermal inflammatory infiltrate with numerous eosinophils.
Treatment
A. Avoidance of future bites with use of protective clothing and insect repellants.
B. Attention to eradicating the source of the biting insects, such as on pets, nests, etc.
C. Supportive local care to prevent secondary infection and relieve pruritus.
Alternative Diagnosis: Bullous Pemphigoid
Textbook Presentation
Bullous pemphigoid is usually seen in elderly patients with the sudden onset of 1–2 cm tense blisters and bright red, urticarial plaques. Lesions often begin on the lower extremities and progress upward.
Disease Highlights
A. Description of the lesion: tense bullae arising on skin that may be normal, erythematous, or urticarial (Figure 29-8).
Figure 29-8. Bullous pemphigoid. (Used with permission from Dr. Duri Yun.)
B. Bullous pemphigoid is an autoimmune disease primarily affecting the elderly.
C. Autoantibodies are targeted against components of the epidermal basement membrane zone, thus triggering separation and blistering.
D. The lesions heal without scarring.
E. Most cases occur sporadically without obvious precipitating factors.
F. Character and location of the lesion
1. Predilection of blisters for the extremities
2. Lesions range from asymptomatic to intensely pruritic.
3. Mucosal surfaces are rarely involved.
G. Other blistering syndromes, such as pemphigus vulgaris and epidermolysis bullosa acquisita, are caused by antibodies to other elements of the basement membrane zone.
Evidence-Based Diagnosis
A. Histopathology provides supportive information, demonstrating a subepidermal blister plane and accumulation of eosinophils.
B. Immunopathology confirms the diagnosis by demonstrating linear deposits of IgG and C3 at the dermal-epidermal junction.
C. In 70–80% of patients, circulating IgG that recognizes the identified antigens of the basement membrane zone can be found.
Treatment
A. Topical, potent corticosteroids can be effective.
B. Extensive disease can be treated with systemic corticosteroids.
C. Steroid-sparing immunosuppressives are used to limit the toxicities of systemic corticosteroids in chronic disease.
D. Alternative anti-inflammatory agents, such as tetracycline and nicotinamide, may be effective.
E. Remission is usually obtained within a few weeks; however, some degree of long-term therapy may be necessary.
F. Refractory cases may respond to plasmapheresis, intravenous gammaglobulin, or rituximab.
Alternative Diagnosis: Stevens-Johnson Syndrome
Textbook Presentation
Stevens-Johnson syndrome typically presents in a patient with fever, malaise, headache, and myalgias who is taking a potentially causative medication. After about 1 week of symptoms, a macular rash develops on the chest and face. These lesions subsequently blister and then rapidly erode. The skin is usually excruciatingly tender.
Disease Highlights
A. Description of the lesion: flaccid bullae and vesicles that develop centrally within preexisting target lesion. The bullae rapidly erode, leaving red and raw skin (Figure 29-9).
Figure 29-9. Stevens-Johnson syndrome.
B. Stevens-Johnson syndrome and toxic epidermal necrolysis are hypersensitivity reaction patterns involving the skin.
1. These 2 conditions are often considered to be on a spectrum of severity. Stevens-Johnson syndrome involves less body surface area, whereas toxic epidermal necrolysis leads to considerable areas of full-thickness skin sloughing.
2. Although the precise cause has not been found, drugs are involved in most cases.
C. More than 200 drugs have been implicated as causes of Stevens-Johnson syndrome and toxic epidermal necrolysis.
D. An older, but well-done case-control trial identified common culprits. These are listed in Table 29-3 with their associated ORs.
Table 29-3. Medications most commonly implicated in Stevens-Johnson syndrome or toxic epidermal necrolysis.
E. Disease course
1. Prodromal symptoms, characterized by fever, malaise, headache, myalgias, as well as gastrointestinal and respiratory complaints, occur over 1–2 weeks.
2. The rash occurs initially on the face and central trunk as pink to red macules and papules.
3. The rash may spread and evolve rapidly, with individual lesions becoming targetoid with dusky centers and ultimately coalescing into larger plaques.
4. Flaccid bullae and vesicles may develop centrally within targets as the skin necroses.
5. Blisters form and rapidly erode leaving red and raw skin that becomes coated by a gray-white pseudomembrane.
6. Mucous membranes
a. Lesions on mucous membranes may accompany or precede the skin rash.
b. The mucosal surfaces may be tender and burning.
c. The lips are often swollen, cracked, bleeding, and crusted.
F. A hallmark of Stevens-Johnson syndrome and toxic epidermal necrolysis is the presence of exquisite skin tenderness.
Evidence-Based Diagnosis
A. Histopathology supports the clinical impression.
B. Pathology demonstrates epidermal necrosis with minimal evidence of epidermal and dermal inflammation.
Treatment
A. If an offending drug is present, it must be discontinued.
B. Supportive care in a burn unit is optimal.
C. Surveillance for secondary infection is critical.
D. Immunomodulating drugs have been proposed for use early in the course of the disease to abort epidermal necrosis and disease progression; however, clear benefit has not been confirmed.
E. Use of systemic corticosteroids is controversial. Studies have not proven that the benefit outweighs the risk of immunosuppression.
CASE RESOLUTION
PCR for VZV was positive, thus confirming the diagnosis of varicella zoster. The patient was prescribed valacyclovir for 7 days. He was instructed to keep the skin lesions covered to prevent contacts from being exposed to the infectious vesicle fluid. He was counseled to avoid close contact with young infants and immunosuppressed individuals until all skin lesions are crusted.
CHIEF COMPLAINT
PATIENT
Ms. M is a 16-year-old girl who has many small red flaky spots. The rash developed first on her trunk and over the last 2 weeks is spreading to her extremities (Figure 29-10). She denies any history of similar eruptions. She states she is otherwise feeling well. This eruption is not particularly itchy. On examination, there are many 1–2 cm discrete, brightly erythematous plaques and papules with adherent white scale. The lesions are predominantly on the trunk but extend onto the extremities. Some lesions appear somewhat linear in configuration, whereas most are round to oval in shape. The scale is confluent over the surface of the lesions. The nails are normal and the palms and soles are clear. The oropharynx is injected with some tonsillar enlargement but without exudates. The tongue appears geographic. The rest of the physical exam is unremarkable.
At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?
Figure 29-10. Ms. M on initial presentation.
RANKING THE DIFFERENTIAL DIAGNOSIS
The appearance of the eruption suggests that this condition is papulosquamous in morphology, meaning that the eruption is composed primarily of papules and plaques with scale. Common causes of papulosquamous eruptions are psoriasis, pityriasis rosea, fungal infections, and nummular dermatitis.
The patient’s age, acute onset of the rash, and the pattern of small papules and plaques are pivotal points suggesting either guttate psoriasis or pityriasis rosea. In addition, the finding of pharyngeal injection suggests that there may be an infectious component (as is common with guttate psoriasis). The configuration of the lesions and the scale can be very helpful in narrowing the differential diagnosis. This patient’s scale is confluent over the surface of the lesions, consistent with guttate psoriasis. Tinea infections typically have scale at the border of the lesions (leading edge with advancing scale) and pityriasis rosea has scale at the center of the lesion (trailing scale). Nummular dermatitis is usually found on the extremities and is associated with significant pruritus, making it an unlikely diagnosis in this case. Secondary syphilis needs to be considered as a “must not miss” diagnosis. Syphilis can present with plaques, but they often involve the palms and soles and lack an adherent scale (Table 29-4).
Table 29-4. Diagnostic hypotheses for Ms. M.
On further questioning, the patient does recall a sore throat several weeks ago. Her medical history is unremarkable. Her family history is remarkable for a father with psoriasis.
Is the clinical information sufficient to make a diagnosis? If not, what other information do you need?
Leading Hypothesis: Guttate Psoriasis
Textbook Presentation
Guttate psoriasis generally presents with small, round or oval lesions on the back and trunk. The lesions often have somewhat silvery, adherent scales.
Disease Highlights
A. Description of lesion: small (0.5–1.5 cm), round or oval lesions with characteristic overlying silvery scales (see Figure 29-10).
B. Character of the lesion
1. Lesions tend to occur over the upper trunk and proximal extremities.
2. Face, ears, and scalp may also be involved.
3. The lesions may localize to sites of minor skin trauma, such as scrapes (Koebner phenomenon).
4. Eruption generally persists for 3–4 months and then remits spontaneously.
C. Most commonly seen in young adults, frequently preceded by a streptococcal throat infection.
D. Affected patients are at increased risk for development of psoriasis vulgaris in the next 3–5 years.
E. There is an increased incidence of psoriasis in families.
Evidence-Based Diagnosis
A. The diagnosis is often made based on the clinical presentation.
B. The presence of streptococcal pharyngitis would be a supportive finding.
C. A skin biopsy of an established lesion may demonstrate classic histologic findings of psoriasis vulgaris.
Treatment
A. Guttate psoriasis is typically a self-limited eruption, although clearance can take weeks to months.
B. Remission can be hastened with the use of UV light treatments.
C. If there is an infectious trigger, appropriate antibiotics should be administered.
D. Antibiotics with anti-inflammatory properties, such as erythromycin and tetracycline, can be additionally helpful for flares.
E. Topical corticosteroids can be effective on individual lesions.
F. Systemic corticosteroids should be avoided in psoriasis because withdrawal may trigger flares.
G. Topical calcipotriene, a vitamin D derivative, is also effective.
MAKING A DIAGNOSIS
Based on the lesions’ morphology, family history, and recent pharyngitis, guttate psoriasis was considered the likely diagnosis. A throat culture was sent. A skin biopsy was considered but not performed.
Have you crossed a diagnostic threshold for the leading hypothesis, guttate psoriasis? Have you ruled out the active alternatives? Do other tests need to be done to exclude the alternative diagnoses?
Alternative Diagnosis: Pityriasis Rosea
Textbook Presentation
Pityriasis rosea commonly presents with multiple small, oval, scaly plaques on the trunk and proximal extremities. A “herald patch,” the first lesion to develop, is often the largest lesion and may precede onset of other lesions by several weeks. The rash may be pruritic.
Disease Highlights
A. Description of lesion: oval or round plaque with central (trailing) scale (Figure 29-11).
Figure 29-11. Pityriasis rosea.
B. Character of the lesion
1. The primary eruption appears as a single oval or round, pink to brownish plaque with a collarette of scale around the inner margin of the lesion (the herald patch). This herald patch most often occurs on the trunk and is often misdiagnosed as tinea corporis.
2. One to 2 weeks after the appearance of the herald patch, the secondary eruption emerges as generalized smaller but similar oval scaly plaques distributed along skin tension lines in a “fir tree” pattern.
3. Variable degrees of pruritus
4. Spontaneous resolution occurs over 8–12 weeks, often with subsequent postinflammatory hypopigmentation or hyperpigmentation.
C. A history of a prodrome of mild symptoms of malaise, nausea, headache, and low-grade fever may be present.
D. Pityriasis rosea is a common worldwide disease without genetic or racial predilection, occurring sporadically throughout the year.
E. A viral cause is postulated; evidence suggests but does not confirm a role for human herpesvirus 7.
Evidence-Based Diagnosis
A. The diagnosis is clinical, based on morphology and distribution of the skin lesions.
B. Skin biopsy demonstrates nonspecific findings of a subacute dermatitis but can provide supportive evidence for the diagnosis.
Treatment
A. No specific treatment is indicated or effective; the condition resolves over 8–12 weeks.
B. In cases with severe pruritus, symptomatic treatment such as antihistamines or low potency topical corticosteroids may be beneficial.
C. UVB phototherapy has been advocated to decrease the severity, particularly when administered early in the course. This treatment may worsen the postinflammatory dyspigmentation.
Alternative Diagnosis: Tinea Corporis
Textbook Presentation
Tinea corporis commonly presents as round, pink plaques with small peripheral papules and a rim of scales. The neck and back are the most common locations (Figure 29-12).
Figure 29-12. Tinea corporis.
Disease Highlights
A. Description of the lesion: multiple lesions are possible.
1. Circular lesions with a sharply marginated raised border and central clearing, arising by centrifugal spread of the fungus from the initial site of infection
2. Inflammatory lesions may demonstrate pustules or vesicles, especially around the margin.
3. Overlying scale is common, typically more prominent at the border of the lesion.
4. Solitary lesions may occur, or there may be multiple plaques that remain discrete or become confluent.
B. The degree of associated inflammatory change is variable, depending on the causative species of fungus.
C. The wide variation in clinical presentation depends on the species of fungus, size of the inoculum, body site infected, and immune status of the patient.
Evidence-Based Diagnosis
A. Microscopic identification of fungal elements after application of 5–20% potassium hydroxide (KOH) solution to lesional scrapings collected on a microscope slide
B. Culture of tissue material (such as lesional scrapings)
C. Histopathology is rarely necessary to make the diagnosis of a superficial infection, but with the use of special stains (periodic acid-Schiff or Gomori methenamine silver) the fungal elements may be visible in fixed sections.
Treatment
A. Both topical and systemic antifungal agents are effective. The choice is determined by the extent and location of the infection.
B. Hair-bearing sites often require systemic therapy.
Alternative Diagnosis: Nummular Dermatitis
Textbook Presentation
Nummular dermatitis generally presents as an extremely pruritic rash of numerous, round, crusted lesions on the lower extremities.
Disease Highlights
A. Description of lesions: well-demarcated coin-shaped lesions composed of minute vesicles and papules on an erythematous base. The lesions have an overlying crust, frequently with a weeping exudate (Figure 29-13).
Figure 29-13. Nummular dermatitis.
B. Nummular dermatitis is an acute eruption of numerous lesions predominantly on the extremities.
C. The lesions are severely pruritic.
D. The eruption runs a remitting and relapsing course.
E. Patients are often atopic.
F. Secondary infection is frequently present.
Evidence-Based Diagnosis
A. Microscopic examination of a scraping will rule out tinea.
B. Histopathology can assist in the diagnosis by demonstrating the features of an acute dermatitis.
Treatment
A. Topical corticosteroids target the acute inflammation.
B. If present, secondary infection is efficiently managed with systemic antibiotics.
C. Antihistamines can help alleviate the pruritus until the inflammation is adequately controlled.
D. Skin care, especially bathing practices and appropriate use of emollients, should be emphasized.
Alternative Diagnosis: Secondary Syphilis
Textbook Presentation
Secondary syphilis presents as oval macules. The lesions are present diffusely, including on the palms and soles. A history of a transient, painless, genital ulcer in the preceding weeks can often be obtained.
Disease Highlights
A. Description of lesion: papules and plaques distributed over the entire body. They are copper red to hyperpigmented in color.
B. Character of the lesion
1. Lesions may vary at different stages of disease.
a. A fleeting eruption of symmetric, coppery red, round and oval macules may be seen early in the secondary stage, about 8 weeks after the infecting exposure.
b. The later, classic eruption includes involvement of mucosal surfaces and palms and soles.
c. In the latest phases, thick scales may cover the plaques.
2. The rashes of secondary syphilis are nonpruritic.
3. The lesions are generally symmetrically distributed.
Evidence-Based Diagnosis
A. Tests for syphilis include non-treponemal and treponemal tests.
1. Non-treponemal tests assess the reactivity of serum to a cardiolipin-cholesterol-lecithin antigen. They include the rapid plasma reagin (RPR) and the venereal disease research test (VDRL).
2. Treponemal tests are qualitative tests (“reactive” or “nonreactive”) that detect antibodies directed against specific treponemal antigens. They include the fluorescent treponemal antibody (FTA), microhemagglutination Treponema pallidum (MHA-TP), and Treponema pallidum enzyme immunoassay (TP-EIA).
3. Treponemal tests are more specific than non-treponemal ones.
B. Syphilis diagnosis is based on both treponemal and non-treponemal tests. Most laboratories employ algorithms that use a treponemal test as the screening test followed by a non-treponemal test for confirmation if the treponemal test is positive.
Treatment
Penicillin is the treatment of choice for secondary syphilis.
CASE RESOLUTION
The patient’s throat culture revealed group A streptococcus. A clinical diagnosis of guttate psoriasis was made. The patient was prescribed 10 days of penicillin as well as topical corticosteroids and topical calcipotriene. UVB treatments, 3 times weekly, were begun to induce remission of the psoriatic flare. She was counseled on her risk for future development of psoriasis vulgaris.
Guttate psoriasis affects those with a predisposition toward psoriasis. The guttate flares tend to remit quite reliably; however, affected individuals are at increased risk for the development of chronic psoriasis.
OTHER IMPORTANT CUTANEOUS DISORDERS
Urticaria
Textbook Presentation
Urticaria typically presents as an itchy rash with large or small, palpable, red areas over the entire body. The rash is transient, with no 1 lesion lasting very long. Both the rash and the pruritus respond to antihistamines.
Disease Highlights
A. Description of the lesion: transient pink to red gently elevated edematous papules and plaques that may coalesce into giant lesions. The lesions often leave purple discoloration or central clearing when they fade (Figure 29-14).
Figure 29-14. Urticaria.
B. Characteristics of the lesion
1. Individual lesions should resolve within 24 hours while new lesions may continue to develop.
2. The eruption is typically accompanied by itch, but excoriations are rare.
C. Mucous membranes, eyelids, hands, and feet may develop deeper subcutaneous swelling manifesting as angioedema.
D. Most urticaria is acute, lasting < 6 weeks.
E. Urticaria is a hypersensitivity reaction to numerous insults.
1. Etiologic factors can be remembered with the mnemonic I-I-I-I-I.
a. Infection
b. Infestation
c. Ingestion (food or drug)
d. Inhalation
e. Injection
2. Idiopathic should be added to this list.
F. Chronic urticaria (lasting > 6 weeks) can also be idiopathic, or associated with systemic disorders such as collagen vascular disease, malignancy, parasitosis, and chronic infection.
Evidence-Based Diagnosis
A. Clinical findings of typical transient urticaria are diagnostic, and a skin biopsy is rarely indicated.
B. The morphologic differential diagnosis often includes the following:
1. Erythema multiforme (because of the targetoid appearance of some urticaria)
2. Insect bite reactions
3. The early phases of bullous pemphigoid
C. Urticaria can be distinguished from all of the above disorders because it is the only one with lesions that last < 24 hours.
D. A careful history, including review of medications, recent exposures, and food ingestion, is the most important aspect of the evaluation to determine a cause.
E. Laboratory evaluation is sometimes undertaken in cases of chronic urticaria, but studies have shown that relevant results are so rarely found without other symptoms that this approach is discouraged.
Treatment
A. Identification of the inciting agent (medication, supplement, infection) is paramount and should be addressed as the first step in management.
B. Antihistamines are the mainstay of therapy. H1-blockers should be given on a regular dosing schedule until the eruption is suppressed and then tapered gradually to prevent rebound flare.
C. Combinations of different H1-blockers can be effective when a single agent is inadequate.
D. Addition of H2-blockers may be helpful in refractory cases.
Purpura/Petechiae
Textbook Presentation
Purpura and petechiae are seen in patients with bleeding diatheses or vascular damage. Petechiae are capillary hemorrhages that present as nonblanching, pinpoint, red spots over dependent body parts, most commonly the lower extremities. They are often associated with severe thrombocytopenia. Purpura are larger hemorrhages into the skin. Purpura are associated with a variety of life-threatening diseases, such as vasculitis and sepsis.
Disease Highlights
A. Description of the lesion: petechiae are red, blue or purple, nonblanching, pinpoint spots. Purpura are larger (up to several centimeters) nonblanching macules, papules, or plaques that may or may not be palpable (Figure 29-15).
Figure 29-15. Purpura.
B. Both purpura and petechiae are, to some degree, nonblanching (ie, the color cannot be compressed out of the lesion by pressure).
C. The shape of these lesions is variable, ranging from stellate to round or oval or targetoid to retiform (netlike).
D. The color, texture, and configuration of these lesions will be helpful in constructing a differential diagnosis of the cause.
E. The differential diagnosis of purpura/petechiae is vast, and many classification schemes have been proposed. The first step is to differentiate ecchymoses from purpura and petechiae.
F. Ecchymoses
1. Ecchymoses are the most common form of hemorrhage in the skin.
2. They are typically induced by trauma and, therefore, are seen on trauma-prone sites, such as the dorsal hand, forearm, lateral thigh, and shin.
3. The shape of ecchymoses tends to be geometric (rectangular) or linear because they are induced by an external force.
4. Predisposing factors to ecchymoses include weakening of the dermal structure secondary to age, corticosteroid use, solar damage, and vitamin C deficiency (scurvy) as well as coagulation defects.
G. Petechiae are most commonly associated with thrombocytopenia.
H. Purpura
1. Like petechiae, purpura signify hemorrhage into the skin.
2. The hemorrhage may
a. Be simple extravasation through leaky vessel walls.
b. Be accompanied by inflammation that is damaging vessel walls. (These lesions are often partially blanching because the inflammatory component blanches while the hemorrhagic component does not.)
c. Be the result of occlusion of a vessel leading to ischemic damage to the skin.
3. The degree to which purpuric lesions are palpable is helpful diagnostically.
a. Nonpalpable hemorrhage in the skin is most concerning for thrombocytopenia or abnormal platelet function.
b. Extravasation of blood alone into deep tissue layers can produce a nodule (such as occurs with a hematoma).
c. Edema associated with the vessel injury (such as in cases of inflammatory vasculitis) may cause a palpable lesion.
(1) Palpable purpura can be a sign of serious, potentially life-threatening, illness (eg, Rocky Mountain spotted fever, acute meningococcemia, disseminated gonococcal infection).
(2) Evaluation should include tests for vasculitis and, in the right setting, infectious causes (possibly including empiric treatment).
Evidence-Based Diagnosis
A. An evaluation of clotting (platelet number, function, and measures of coagulation) is indicated to determine whether purpura and petechiae are symptoms of a coagulopathy, thrombocytopenia, or vasculitis.
B. A skin biopsy can be helpful in determining
1. The size and location of affected vessels within the dermal and subcutaneous tissues
2. The degree and character of associated inflammation
3. The type of vessel damage (leukocytoclastic or granulomatous)
4. The presence and character of any occlusions within vessels (organisms, calcium, fibrin)
C. Immunofluorescence studies of histologic specimens can be helpful in identifying antibody and complement deposits on vessels walls.
Treatment
A. Treatment is directed toward management of the underlying cause of the vessel damage.
B. Supportive therapy includes local wound care and prevention of secondary infection.
Skin Cancer
There are innumerable specific forms of skin cancer, deriving from all of the structures of the skin and subcutaneous tissues. In addition, many cancers will metastasize to the skin. The 3 most common primary skin cancers are basal cell carcinoma, squamous cell carcinoma, and melanoma.
1. Basal Cell Carcinoma
Textbook Presentation
Basal cell carcinoma most commonly presents as a flesh-colored, translucent, or slightly red papule or nodule, classically displaying a rolled border. It most commonly presents on the head or neck of older adults.
Disease Highlights
A. Description of lesion: the typical lesion is a flesh-colored, translucent, or slightly red papule or nodule, classically displaying a rolled border (Figure 29-16).
Figure 29-16. Basal cell carcinoma. (Used with permission from Dr. Anne E. Laumann.)
1. Lesions are often friable, bleeding easily and developing crust. Telangiectasias on the surface can be a helpful sign.
2. Large tumors can be locally destructive.
B. Basal cell carcinoma is the most common malignant tumor in humans.
C. Lesions are typically asymptomatic except for the observation of easy bleeding from a site.
1. Only rarely is pain associated.
2. Metastasis from a basal cell carcinoma is rare.
D. Individuals at risk are adults with fair hair and eyes, easy freckling, and propensity for sunburn.
1. Patients with skin of color are less likely to be affected.
2. Men and women are about equally affected.
3. Exposure to UV light has long been believed to play a causative role in the development of this tumor, although the exact mechanism is not clear. Several genetic mutations have been isolated in basal cell carcinoma and may serve as targets for therapeutics.
4. Chronic wounds and sites of inflammation, as well as, immunosuppression can predispose to development of this tumor.
5. Exposure to arsenic is another risk factor for basal cell carcinoma.
E. The head and neck are the most common sites affected with this tumor.
1. Only 10–15% of tumors develop on sun-protected skin.
2. The nose is the most common site, accounting for 20–30% of all cases.
F. Basal cell carcinoma is likely derived from the hair follicle. The name implies a resemblance of the tumor cells to the basal cells of the epidermis, although this is not believed to be their derivation.
G. Patients have up to a 45% risk of developing subsequent basal cell carcinomas in the 5 years after initial diagnosis.
Evidence-Based Diagnosis
Histologic evaluation of affected tissue is the gold standard for diagnosis.
Treatment
A. The goal of therapy is to eliminate the tumor and prevent local tissue destruction. Numerous methods are available to accomplish this goal, and selection depends on tumor size, type, and location, patient characteristics, and patient preferences.
B. 5-year recurrence rates vary by treatment modality. The lowest recurrence rate is achieved with Mohs micrographic surgery.
1. This method involves excision of the visible tumor, followed by microscopic evaluation of frozen tissue sections to visualize tumor margins and repeat local excision until all margins are clear of tumor.
2. The technique allows for maximal tissue sparing while ensuring complete eradication of tumor.
C. Follow-up of patients for recurrent or subsequent tumors is critical.
2. Squamous Cell Carcinoma
Textbook Presentation
Squamous cell carcinoma most commonly presents as a firm but somewhat indistinct nodule or plaque. It may evolve from actinic keratoses on the sun-exposed skin of middle-aged people.
Disease Highlights
A. Description of lesion: lesions are firm but somewhat indistinct nodules or plaques that may arise from an in situ carcinoma or in normal skin. Tumors may become ulcerated or bleed easily and become crusted (Figure 29-17).
Figure 29-17. Squamous cell carcinoma. (Used with permission from Dr. Anne E. Laumann.)
1. The surface may be smooth, verrucous, or papillomatous, with or without scaling.
2. Fixation to underlying structures develops as the lesion invades locally.
3. In situ lesions tend to be sharply demarcated erythematous scaling plaques.
B. This tumor most commonly affects fair-skinned individuals with excessive sun exposure.
1. May evolve from actinic keratoses on sun-exposed skin in these patients.
2. UV radiation is a major risk factor for the development of this tumor.
3. Additional predisposing factors include
a. Radiation therapy
b. Chronic scar formation
c. Chemical carcinogens, such as hydrocarbons
d. Viral exposures
e. Thermal exposures
f. Arsenic
g. Long-term immunosuppression (such as in kidney transplant recipients).
C. Squamous cell carcinoma does carry a risk of local recurrence and metastasis.
1. The risk of local recurrence is around 3%.
2. Metastasis is less common but can reach 10% in patients with the thickest lesions.
3. Other factors, such as location (ears) and immunosuppression, are also associated with higher risk of metastasis.
D. Intraoral squamous cell carcinoma is predominantly a disease of adult men.
1. Risk factors are alcohol and tobacco use as well as HPV infection.
2. When detected in the early asymptomatic stage, these cancers are easily curable.
E. Incidence increases with age and varies with geographic location, ethnicity, and behavior patterns.
Evidence-Based Diagnosis
A. Histologic evaluation of affected tissue is the gold standard for diagnosis.
B. A high index of suspicion may be necessary to recognize a potential tumor when its appearance or location is unusual. For example, the verrucous form of squamous cell carcinoma can be mistaken for a wart.
Treatment
A. The goal of treatment is eradication of the tumor while producing the least disability and dysfunction for the patient.
B. Careful evaluation for the presence of metastatic disease is paramount. This may include lymph node dissection in some instances.
C. Multiple destruction modalities are available and are selected based on size, shape, and location of the tumor as well as patient preferences. These modalities include, but are not limited to
1. Surgical excision
2. Mohs micrographic surgery
3. Electrosurgery
4. Radiation therapy
5. Local immunotherapy
D. Wide destruction of these tumors usually results in cure as squamous cell carcinomas grow by direct extension. However, residual tumor can invade and extend along peripheral nerves, occasionally resulting in a deep recurrence.
E. A large percentage of squamous cell carcinomas could be prevented by avoidance of excessive solar exposure. Routine screening for tumors, especially in high-risk patients, is imperative.
3. Melanoma
Textbook Presentation
Melanoma typically presents as a dark brown or black macule or papule in a middle-aged person. The lesion has pigment variation throughout and irregular borders.
Disease Highlights
A. Description of lesion: the most common type of melanoma is superficial spreading (Figure 29-18).
Figure 29-18. Malignant melanoma. (Used with permission from Dr. Anne E. Laumann.)
1. These tumors may present as a dark brown to black macule or thin plaque, typically with pigment variation throughout and irregular borders.
2. With growth, the surface becomes glossy.
3. The most common location of superficial spreading melanomas is on the upper back in males and the leg in females.
B. These cancers are most commonly diagnosed in the fourth and fifth decades of life.
C. Melanoma may arise in a preexisting melanocytic nevus or de novo.
D. Multiple subtypes exist, including lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, acral lentiginous melanoma, and amelanotic melanoma, among others.
1. Nodular melanoma is the second most common type of melanoma.
a. Presents most often on the head, neck, or trunk.
b. These tumors evolve rapidly over months.
c. They appear as a blue-black, reddish, purplish, or even a nonpigmented papule or nodule.
2. Acral lentiginous melanoma is the predominant type of melanoma seen in the more pigmented races, such as Africans, Asians, and Indians.
a. Acral lentiginous melanoma occurs on the palms and soles and beneath the nail plate.
b. Diagnosis of these lesions is often delayed; therefore, they are often of a more advanced stage at diagnosis.
c. Affected individuals tend to be older.
3. Lentigo maligna melanoma is a rare type of melanoma found predominantly in the elderly on the sun-exposed portions of the head and neck.
a. The tumor is usually flat, with irregular borders and a diameter of several centimeters.
b. Color varies throughout from tan to brown to black and purple and blue.
E. Melanoma is a tumor of melanocytes.
1. Benign pigmented nevi are composed of altered melanocytes, termed “nevomelanocytes.”
2. Malignant transformation of melanocytes and nevomelanocytes can result in melanoma, arising de novo from normal skin, or from a preexisting nevomelanocytic lesion (nevus or mole).
F. The incidence of cutaneous melanoma is increasing steadily in the United States.
1. In 1935, the lifetime risk of an American developing melanoma was 1 in 1500 individuals, whereas in 2016 the lifetime risk of being diagnosed with invasive or in-situ melanoma was 1 in 28.
2. An estimated 96,480 Americans will be diagnosed with melanoma in 2097, and 7230 will die of the disease.
3. There has been a substantial rise in overall 5-year survival in patients with melanoma since the 1970s.
a. The improved survival may be due to earlier diagnosis as well as improved treatment and surgical techniques.
b. The rising incidence and improved outcomes raise the possibility of overdiagnosis.
G. Whites are 26 times more likely to develop melanoma than blacks. Worldwide, whites have the highest risk of developing melanoma, and Asian populations have the lowest risk.
H. Epidemiologic studies strongly suggest that sun exposure is a major risk factor for the development of cutaneous melanoma in the light-skinned populations.
1. Intense intermittent episodes of sun exposure before 18 years of age are thought to engender the highest risk in susceptible populations.
2. Phenotypic features have been associated with increased risk for cutaneous melanoma: light skin pigmentation, ease of sun burning, blond or red hair, prominent freckling, and blue or green eyes.
I. Familial melanoma accounts for 8–12% of cases. Those with at least 2 first-degree relatives with a history of melanoma are at particularly high risk.
J. Dysplastic nevi (clinically atypical appearing nevi) are thought to be markers of an individual with an increased risk of developing cutaneous melanoma.
1. The number of nevi on the body has been directly correlated with the magnitude of melanoma risk.
2. About one-third of melanomas have been associated with an underlying nevus.
K. Recurrences of disease generally occur in a stepwise manner, first locally, then in regional lymph nodes, and lastly as distant metastases.
Evidence-Based Diagnosis
A. An excisional biopsy is the preferred method for obtaining tissue for diagnosis. This preserves the extent of the primary tumor and all associated histologic features without disrupting the lymphatic architecture.
B. Full-thickness incisional or punch biopsies of lesions too large to excise fully or in anatomically sensitive locations are satisfactory.
C. The histologic diagnosis of melanoma is based on a constellation of features; no single feature is diagnostic. Both cytologic and architectural features are evaluated.
D. The staging system for melanoma follows the tumor, node, metastasis (TNM) system, which relies on assessment of the primary tumor, regional lymph nodes, and the presence or absence of distant metastases. Assessment of the primary tumor focuses on the histologic tumor thickness and presence of ulceration as the most important initial variables.
Treatment
A. Management of cutaneous melanoma is guided by stage of disease. Wide excision of tumors is the general rule.
B. Sentinel lymph node mapping may be beneficial diagnostically in more advanced stages, decreasing the complications associated with full lymph node dissections.
C. Adjuvant treatment options for advanced stage disease include
1. Immunotherapy using checkpoint inhibitors (pembrolizumab, nivolumab, ipilimumab) and targeted therapy (inhibition of BRAF and/or MEK genes) are first line.
2. Radiation therapy may have a palliative role for symptomatic localized areas of disease.
3. Cytotoxic chemotherapy has not been shown to improve overall survival in patients with advanced melanoma.
D. Follow-up of melanoma patients is critical to detect recurrences as well as new primary tumors and to provide ongoing education.
E. Melanoma prevention strategies focus on education about the risks of UV exposure via sunlight or tanning machines, sun protection guidelines, and the importance of routine self-skin exams.
1. Early detection is important for improving outcomes.
2. Patients should be instructed on the importance of their own skin examination and what constitutes a worrisome mole, easily remembered by the ABCDEs of mole evaluation.
a. A: asymmetry
b. B: borders that are irregular or changing
c. C: color that is irregular or changing
d. D: diameter > 6 mm (or larger than a pencil eraser)
e. E: evolution of the lesion in general
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Summary Table