Disease-a-Month ] (]]]]) ]]]–]]]

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Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth

Clinical pearls in dermatology 2014 Catherine C. Newman, MD, John B. Bundrick, MD

Case 1 A 34-year-old female presents with papulopustular acne. She has tried topical tretinoin, benzoyl peroxide wash, topical clindamycin, and oral doxycycline. She has adhered to her treatment regimen for 3 months without improvement. She has deep, painful, persistent nodules on the jawline, chin, and neck (Fig. 1). Question What is the next best option for treatment? A. B. C. D. E.

Change to oral minocycline Add a salicylic acid wash, 2% Consider hormonal intervention Oral isotretinoin Culture pustule for bacterial resistance

Discussion Acne may begin in adult women who have not experienced teenage acne. The patient should be checked for other signs of androgen excess such as hirsutism, menstrual irregularities, or androgenetic alopecia. However, this type of acne in women with deep nodules on the lower face and neck will often improve with hormonal intervention, even if there are no other clinical signs of androgen excess. The most common cause of treatment failure for acne is lack of adherence to the treatment plan. After ascertaining that the patient is using treatments correctly and yet not improving, it is reasonable to consider hormonal intervention. Oral contraceptives block adrenal and ovarian androgens. The most beneficial ones for acne with FDA approval are as follows:

 

Norgestimate/ethinyl estradiol Drospirenone/ethinyl estradiol

http://dx.doi.org/10.1016/j.disamonth.2014.04.014 0011-5029/& 2014 Mosby, Inc.. All rights reserved.

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Fig. 1. 34-year-old female with papulopustular acne

Spironolactone can also be used as an antiandrogen. It is often used in combination with an oral contraceptive. It is a teratogen and can cause feminization of the developing male fetus. Usual dosing starts at 25 mg daily and can be increased to 200 mg daily, while monitoring serum potassium with dose changes. Clinical pearl Hormonal interventions may be beneficial for acne in women, even in the absence of other clinical signs of androgen excess. References 1. Kamangar F, Shinkai K. Acne in the adult female patient: a practical approach. Int J Dermatol. 2012;51(10):1162–1174. 2. Newman MD, Bowe WP, Heughebaert C, Shalita AR. Therapeutic considerations for severe nodular acne. Am J Clin Dermatol. 2011;12(1):7–14. Case 2 A 45-year-old female complains of recurrent “canker sores.” She notes round white ulcers on the buccal and labial mucosa (Fig. 2). They usually resolve in 10–14 days but are very painful. She has about 10 episodes a year. These interfere with speech and mastication. She is otherwise healthy. Question If you are able to identify an underlying condition, it will most likely be A. Inflammatory bowel disease

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Fig. 2. 45-year-old female with recurrent “canker sores”.

B. C. D. E.

Gluten-sensitive enteropathy Deficiency of folate, B12, or iron Behcet’s syndrome Cyclic neutropenia

Discussion Recurrent aphthous stomatitis (RAS) is most often induced by trauma such as biting gums, brushing, or dental procedures. It can also be induced by spicy foods, citrus, rough foods, emotional stress, or hormone changes. About 10–20% of patients who have been investigated for causes had low folate, B12, or iron. Correction of the abnormality can clear or improve the condition. Most patients should be screened for folate, B12, or iron deficiency. All of the other choices can induce aphthous stomatitis as well but are much less common. Other known causes include HIV, malabsorption syndromes, or IgA deficiency. If the patient has had multiple episodes for many years without other symptoms or changes in health, it is likely not useful to screen for these unusual conditions. However, any patient with new-onset aphthous stomatitis or severe disease should at least have these conditions considered. Clinical pearl Recurrent aphthous stomatitis can be caused by deficiency of folate, B12, or iron. References 1. Chavan M, Jain H, Diwan N, et al. Recurrent aphthous stomatitis: a review. J Oral Pathol Med. 2012;41(8):577–583. 2. Liang MW, Neoh CY. Oral aphthosis: management gaps and recent advances. Ann Acad Med Singapore. 2012;41(10):463–470.

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Case 3 A 45-year-old female complains of recurrent “canker sores.” Her diagnosis is recurrent aphthous stomatitis (RAS). She notes small, painful, white ulcers on the buccal and labial mucosa (Fig. 3). She has about 10 episodes a year. These interfere with speech and mastication. She is otherwise healthy. Her investigation did not reveal any underlying process that would be correctable. She would like to discuss treatment options. Question All of the following treatments would be appropriate, except A. B. C. D. E.

Elixir of Benadryl and Maalox Viscous lidocaine 2% Dexamethasone ointment Valacyclovir Fluocinonide 0.05% gel or fluocinonide compounded in Orabase

Discussion Oral valacyclovir would not be indicated if this is truly RAS and not herpes simplex. Recurrent Herpes simplex normally presents on the vermillion border of the lips instead of the inside the mouth. If the diagnosis is in question, testing for herpes virus can be done with culture, PCR, or direct fluorescent antibody assay. Testing methods may depend on which lab method is used by each institution. While they do not prevent new ulcers from developing, topical steroids are very helpful to speed healing if used early in the course of an episode. There are many forms of topical steroids that may be used for RAS. They can be used up to 4 times daily. Gels are usually the easiest to apply. Ointments can be used. Often providers compound topical steroids with protective barriers such as Orabase.

Fig. 3. 45-year-old female with recurrent “canker sores.”

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The other treatments (elixir of Benadryl/Maalox and viscous lidocaine) are useful for symptomatic relief. Topical steroids can be used in combination with other symptomatic treatments. In severe cases of RAS refractory to topical therapies, many dermatologists will use colchicine. While no adequate randomized placebo-controlled trials have been done to demonstrate its efficacy, there was a suggested benefit in an uncontrolled case series of 55 patients with severe RAS ( 410 episodes per year). Clinical pearl Topical steroids can be helpful in recurrent aphthous stomatitis. References 1. Liang MW, Neoh CY. Oral aphthosis: management gaps and recent advances. Ann Acad Med Singapore. 2012;41(10):463–470. 2. Lynde CB, Bruce AJ, Rogers RS 3rd.Successful treatment of complex aphthosis with colchicine and dapsone. Arch Dermatol. 2009;145(3):273. Case 4 A 17-year-old male has noticed blue spots on his cheeks. He has papulopustular and comedonal acne with mild scarring (Fig. 4). He has been on topical benzoyl peroxide wash, topical clindamycin gel in the morning, topical tretinoin at night, and 100 mg of oral minocycline twice daily for 4 months. Question The most likely cause of the discoloration is A. B. C. D. E.

Secondary venous lake formation Minocycline hyperpigmentation Postinflammatory hyperpigmentation Ochronosis (alkaptonuria) Minocycline-induced photosensitivity

Discussion Minocycline classically induces 3 types of pigmentation. Type I is blue–black discoloration appearing in areas of prior inflammation such as acne, surgical scars, or trauma. Type I is not usually dose or duration dependent. Type II minocycline pigmentation is blue–black pigmentation in normal skin, often the shins. It can also involve the sclera, conjunctiva, bone, thyroid, nail beds, oral mucosa, ear cartilage, or teeth. Type I and Type II usually appear 3 months to 1 year after initiation of minocycline. Type III pigmentation is generalized muddy-brown pigmentation. It is usually accentuated in the sun-exposed areas. This is the least common type. Any of the 3 types of pigmentations will usually fade if the minocycline is stopped early. However, it may take months or even years for complete resolution. It can be hard to differentiate the minocycline-induced blue pigment in scars from postinflammatory hyperpigmentation. However, postinflammatory hyperpigmentation is usually more brown than blue, black, or gray.

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Fig. 4. 17 yo male with blue spots on cheeks.

Clinical pearl Minocycline may cause blue–black hyperpigmentation with long-term use.

References 1. Chatterjee S. Hyperpigmentation associated with minocycline therapy. Can Med Assoc J. 2007;176:322. 2. Bowen AR, et al. The histopathology of subcutaneous minocycline pigmentation. J Am Acad Dermatolol. 2007;57:836. Case 5 A 30-year-old male presents with painful, itching, “cold sore,” or “fever blister” episodes of the lips (Fig. 5). His description of the episodes is compatible with classic herpes simplex virus (HSV)—with a prodrome of pain or itching before the blisters appear. It is usually after a physical or emotional stress or sun exposure. He gets these 4–5 times a year and would like to discuss treatment options.

Question If you feel comfortable with the diagnosis of recurrent HSV, which of the following treatments would be most effective? A. B. C. D. E.

Acyclovir cream Penciclovir cream Tetracaine cream Oral valacyclovir, pulse dosing Use of daily sunblock

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Fig. 5. 30 year-old male with recurrent HSV

Discussion UV light can be a trigger, so sunblock and sun protection can be helpful. The topical acyclovir and penciclovir are proven to reduce the disease duration and pain by 1 day or less. The topical tetracaine would be used for pain management only. If the patient has significant symptomatic outbreaks 6 times per year or less, they are a candidate for pulse valacyclovir, which is far more effective than the other listed treatment options. If they have more than 6 episodes per year, then suppressive therapy may be a consideration. Pulse therapy is given as soon as the patient recognizes the onset of an episode. They may feel the prodrome or note early blisters. Valacyclovir 2 g twice daily is given for 1 day. The patient takes 2 g at the first onset of any symptoms or suspicion of an outbreak and repeats the dose 12 h later. This may completely prevent the blister from appearing. If there are blisters, they may be smaller than usual and heal faster. Clinical pearl High-dose, short-duration early valacyclovir is very effective for episodic treatment of cold sores. Reference 1. Spruance SL, Jones TM, Blatter MM, et al. High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of 2 randomized, placebo-controlled, multicenter studies. Antimicrob Agents Chemother. 2003;47(3):1072–1080. Case 6 A 65-year-old man complains of chronic scaling pruritic rash of both lower legs. He states that he gets “recurrent infections” of both lower legs. On exam, he has erythema, light brown

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pigmentation, eczematous weeping dermatitis, and 1 plus pitting edema of the lower third of the lower legs (Fig. 6). His jugular venous pressure is normal.

Question The patient will likely benefit from all of the following, except A. B. C. D. E.

Acute diuresis Compression therapy Emollients Horse chestnut extract (aescin) Topical steroids

Discussion Chronic venous insufficiency results from increased pressure of the venous system. There are often insufficient valves of the deep venous system or lower perforating veins. Chronic edema leads to fibrosis, thickened skin, or dermatitis. There is a high rate of contact allergy from the usage of multiple topical products. This condition may often be misdiagnosed as cellulitis. However, stasis dermatitis is generally bilateral; the process will have been ongoing for years; there is often pitting edema; and the legs should be nontender. Compression therapy can be implemented by means of pressure wraps, unna boots, coban, or compression stockings. Patients should be taught to elevate legs above the heart for at least 1–2 h during waking hours. The edema will be aggravated by long cramped sitting, especially from travel. If there is a central cause of fluid retention (cirrhosis, heart failure, and renal failure), then diuresis may be helpful. However, this patient had no evidence of such a cause, and diuretics are generally not useful for isolated chronic venous insufficiency.

Fig. 6. 65 year-old man with chronic scaling pruritic rash

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Horse chestnut extract (aescin is the active ingredient) helps soften the skin and reduce edema and pain. It is not helpful for marked hyperpigmentation. The most common dosage of horse chestnut is 300 mg of horse chestnut seed extract twice daily, standardized to contain 50mg aescin per dose, for a total daily dose of 100 mg of aescin. Clinical pearl Stasis dermatitis may be misdiagnosed as cellulitis and also overtreated with diuretics. In addition to compression, horse chestnut seed extract may be beneficial. References 1. Keller EC, Tomecki KJ, Alraies MC. Distinguishing cellulitis from its mimics. Clev Clin J Med. 2012;79(8):547–552. 2. Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. 2012;11:CD003230. Case 7 A 33-year-old female complains of cosmetically bothersome brown patches on the malar prominences and forehead (Fig. 7). She is not pregnant and not on any photosensitizing medications. She denies associated rash, flaking, or itching. Question Which of the following is least likely to help her? A. B. C. D. E.

Complete sun avoidance, sunblock, and broad spectrum UVB and UIVA coverage Nightly tretinoin cream Topical 4% hydroquinone Tri-Luma (combination of tretinoin, hydroquinone, and topical steroid) Measuring her levels of estradiol and FSH

Discussion Sun exposure is the primary trigger for melasma. Prevalence increases with age, genetic predisposition, and female hormones. Melasma occurs frequently with pregnancy, oral contraceptives, and hormone replacement therapy. Melasma of pregnancy clears quickly after birth. Other forms of melasma, particularly hormone induced, often take years to clear. Surgical procedures and peels can be helpful but must be done very carefully to avoid irritation, which will aggravate the pigmentation and exacerbate the condition. While melasma is known to occur with hormonal changes, clinical evidence to date does not clearly associate serum hormone levels to melasma. For women who note the onset of melasma after beginning a course of an oral estrogen, the medication should be stopped if they wish to avoid progression of the pigmentation. Clinical pearl Although the use of exogenous estrogens should be reviewed in women with melasma, it is not clinically useful to check levels of serum estrogens. Strict sun avoidance and use of topical therapies are the mainstays of treatment.

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Fig. 7. 33 year-old female with brown patches on malar prominences and forehead

References 1. Sheth VM, Pandya AG. Melasma: a comprehensive update: Part 1. J Am Acad Dermatol. 2011;65 (4):689–697. 2. Nicolaidou E, Katsambas AD. Pigmentation disorders: hyperpigmentation and hypopigmentation. Clin Dermatol. 2012;32(1):66–72. Case 8 An 80-year-old man presents with itchy, spongy red bumps that have not responded to topical steroid, treatment for scabies, or oral antihistamines (Fig. 8). His health is otherwise stable. He has not started any new medications. He has not had any risk factors for insect bite exposure.

Question What is the next step to help establish the cause and diagnosis?

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A. B. C. D. E.

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Look aggressively for bed bugs Biopsy a skin lesion for routine histopathology and direct immunofluorescence (DIF) Treat patient again for scabies and treat family members Check triglyceride levels Trial of low-dose oral corticosteroids

Discussion This patient has bullous pemphigoid (BP). Classic BP is characterized by large, tense, subepidermal bullae with a predilection for the groin, trunk, thighs, and flexor surfaces of forearms. However, BP can sometimes present with itchy red bumps and no blisters. Occasionally, bullous pemphigoid can be manifested as a non-bullous pruritic eruption of polymorphous and non-specific lesions such as erythematous, urticarial papules and plaques. The diagnosis is confirmed by a skin biopsy that shows subepidermal bullae. The DIF shows immunofluorescence along the basement membrane zone. This confirms that the disease is an autoimmune blistering disease with antibodies to the basement membrane of the skin. There are also serologic tests such as bullous pemphigoid antibody 180 and 230 that can be useful for

Fig. 8. 80 year-old man with itchy, spongy red bumps

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diagnosis. These are not usually used alone but in combination with clinical and pathologic findings. Patients with itchy red bumps need to be evaluated for insect bites. Scabies would usually have wrist, finger web, or genital burrows. Triglycerides should be checked if these were thought to be eruptive xanthomas. However, eruptive xanthomas would present as eruptive firm yellow papules that are generally not pruritic. Clinical pearl Bullous pemphigoid can present as small red itchy bumps that do not blister. Reference 1. Kershenovich R, Hodak E, Mimouni D. Diagnosis and classification of pemphigus and bullous pemphigoid. Autoimmun Rev. 2014;11(14):00023–00028.

Answers: 1—C; 2—C; 3—D; 4—B; 5—D; 6—A; 7—E; and 8—B

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