A Triad of Dermatologic Dilemmas

Abstract

The U.S. health care system relies on primary care physicians to provide the majority of the dermatologic care—dermatologists see an estimated 30–40% of patients with dermatologic issues.¹ Issues related to skin and mucous membrane conditions account for an estimated 8% of all visits to Family Physicians.² Thus the primary care physician must be prepared to assess patients’ with conditions benign or malignant, cosmetic or grave, irritants or harbingers of systemic illness, pathological or normal variant. In this article, three commonly seen and difficult to treat conditions will be reviewed.

Angular Chelitis

Also called angular chelosis, commissural chelitis, angular stomatitis or perleche, Angular Chelitis (AC) is an inflammation of the vermilion commissures and adjacent mucous membranes which can rapidly escalate to erythema, moist maceration, ulceration and crusting at the corners of the mouth (See Figure 1). With long-term inflammation, granulation tissue may develop, evolving into diffuse chelitis involving the entire upper and lower lips. Symptoms are soreness, pain, burning, and itching, exacerbated by opening the mouth, and can be unilateral or bilateral. It is most common in adults in the third and sixth decades of life.³

Figure 1.

Angular Chelitis

AC is associated with a variety of local and systemic factors, alone or in combination, but most common are local factors: irritant, allergic, or infectious. Treatment must neutralize the impact of specific local factors on the barrier function.

The most common cause is irritant chelitis due to persistent contact with saliva with maceration and resulting inflammation. Factors leading to this are conditions which lead to deeper than usual fold of skin at the corner of the mouth, such as in edentulous patients or those with damage to elastic tissue due to extensive UV light skin damage or smoking. Other causes include habitual drooling (e.g. post CVA) or chemical irritants from denture cleaning products.³ It is more common in people with underlying eczema with reactive skin.

Allergic AC is less common but should be considered if no irritant cause is found. Nickel-based metals in braces or other oral appliances may be a cause of AC, even in the absence of mucositis. Anything that can cause generalized chelitis (lipstick, toothpaste, sunscreens, and medications such as neomycin) can also cause localized AC.

Whether AC is in part due to infectious causes or if the microorganisms found are just colonizing the inflamed tissue is controversial. Some believe infection to be the most common cause of AC.⁴ Staphylococcal species, Streptococcal species, Candida albicans, and Herpes simplex are the common organisms found.

Less common causes of AC are nutritional deficiencies (iron, B vitamins, Zinc), side effects of pharmaceuticals (isotretinoin and other systemic retinoids, Indinavir, drugs that interfere with B-6 synthesis such as INH), drugs of abuse (cocaine due to compulsive lip smacking, heroin and methamphetamines due to neurotic excoriation), and systemic diseases (Down’s syndrome, xerostomia (from many causes), anorexia, systemic lupus erythematosus, inflammatory bowel disease, uremia, and HIV).⁵

The diagnostic approach to a patient presenting with AC begins with a history of timing, duration, recurrence, exposures, medication use, dental issues, tobacco use, solar damage due to prolonged UV light exposure, and symptoms of systemic illness that may predispose to AC. Examination should include evaluating the extent of the chelitis and associated dental hygiene, signs of pooling of saliva, and any sign of nutritional deficiencies. In select patients, cultures can be considered as well as further laboratory testing for systemic illness or nutritional deficiencies.⁵

Treatment is often not needed and AC resolves on its own.⁵ For persistent symptoms, barrier creams or emollients applied frequently will resolve the condition (e.g., zinc oxide). Addition of a low-potency steroid may help reduce inflammation.⁵ If there is evidence of an infectious agent, topical treatment with antifungals or antibiotics will suffice without systemic treatment. Replacement of ill-fitting dentures or oral appliances may be needed. Addressing nutritional deficiencies will be needed in those unusual cases. If deep folds at the corner of the mouth cause recurrent symptoms, tissue fillers such as collagen or autologous fat may be considered.⁵

Recurrent Aphthous Stomatitis

Aphthae, also called canker sores, have plagued mankind throughout recorded history, first described by Hippocrates (460-370 BCE).7 Recurrent Aphthous Stomatitis (RAS) results in recurrent small round or ovoid symmetric mucosal ulcers with circumscribed margins, erythematous halos and yellow or gray bases (See Figure 2). RAS is the most common inflammatory ulcerative condition of the oral cavity. The point prevalence is 1.23% and the lifetime prevalence is 36.5% based on the National Survey of Oral Health in the USA (1986–1987).⁷ The incidence is higher in children, and if both parents have a history of RAS, 90% of their children will experience it, whereas only 20% of children will have it if neither parent has it. RAS is five times more common in children of high socioeconomic status.⁸ The peak age is 10–19 and de creases over the decades, but can affect people of any age. The etiology is unknown, but several local, systemic, immunologic, genetic, allergic, nutritional, and microbiological factors have been proposed.⁷

Figure 2.

Angular Stomatitis

RAS is more common with trauma—denture wearers have triple the incidence of non-denture wearers. Smokers have lower incidence than non-smokers for uncertain reasons. Change in saliva composition has been suggested as a cause of RAS, such as stress-induced increase in salivary cortisol. Graduates students have been noted to have a higher incidence of RAS, presumably due to the stress of exams, dissertation, etc. However, those same students later become professionals with no higher incidence of RAS than non-professionals, so it may be more age related than stress related.⁷ Evidence for microbial causes have been unconvincing, with EB virus, Herpes virus, and H. pylori all effectively ruled out. However, a T-cell mediated immune response to Streptococcus sanguis 2A may be involved.⁷

A number of systemic conditions may have an RAS-like presentation. Behcet’s disease is a systemic vasculitis multi-organ process with RAS-like ulceration, but also has genital, cutaneous, and ocular symptoms along with renal, neurological, GI, hematological, and joint abnormalities. Other systemic conditions to consider are: mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome; periodic fever, aphthosis, pharyngitis, and adenitis syndrome (PFAPA); Crohn’s disease; ulcerative colitis; celiac disease; HIV infection, and cyclic neutropenia.⁷

Increased stress has been associated with exacerbations of RAS, and some women experience RAS associated with menses.⁷ Genetic predisposition exists as evidenced by the parent-child associations mentioned.

A small subset of patients with RAS may have nutritional deficiencies. The most common deficiencies reported include iron, folate, zinc, and vitamins B-1, B-2, B-6, and B-12.

Drug induced RAS has been reported with NSAIDs and beta-blockers.

Many patients associate certain foods with outbreaks. Some of the more commonly reported foods associated with exacerbations of RAS include: strawberries, chocolate, coffee, peanuts, cheese, tomatoes, citrus fruits, cereals, and almonds. Sodium lauryl sulfate in toothpaste has also been reported as a cause.⁷

Symptoms of RAS begin with a prodromal burning 2–48 hours prior to the redness and white papule which quickly ulcerates and enlarges over the next two days. The ulcerations cause pain with eating, swallowing and speaking. There are three presentations of RAS:

• Minor RAS. This is the most common presentation, representing >85% of cases.⁸ Typically there are 1–5 ulcers < 5mm on the labial or buccal mucosa or floor of mouth, lasting 10–14 days, healing with no scars.

• Major RAS. Uncommon, severe form, also called periadenitis mucosa necrotica recurrens. Oval, >1cm ulcers on lips or soft palate. The ulcers may last six weeks and leave scars. This is a chronic condition with recurrences over 20 years or more.

• Herpetiform RAS. Least common, presenting as multiple recurrent crops of widespread small painful ulcers on the tip of the tongue and the floor and anterior portions of mouth. Usually <2mm in size, but there may be dozens and some may fuse to appear to be larger ulcers. Most common in females and with later onset than the other types.

The diagnosis is usually evident on history and physical examination. No additional testing is indicated in most cases, however, if an adult presents with new onset RAS, consider screening labs (CBC, iron, B-12 and folate levels). If the history or examination suggests a systemic condition, further testing is indicated.

Treatment is aimed at pain relief and healing as well as attempts to decrease recurrence, although few agents have demonstrated efficacy.⁹ A search for triggers is indicated, looking for associated foods, medications, trauma (too firm toothbrush or ill-fitting dentures), or stress. Any nutritional deficiencies suspected should be addressed—it has been suggested that up to 20% of patients have iron deficiency.¹⁰

Puri, Gill, et al. have suggested a therapeutic ladder from topical to systemic.¹¹ Topical agents are used first. Local anesthetics/analgesics are used for pain relief, including lidocaine preparations, benzocaine, tannic acid, and camphor/phenol. If those products are inadequate, topical steroids can be tried, such as triamcinolone 0.1% in adhesive paste, high potency steroids including clobetasol solution 0.05% or fluocinonide solution 0.05% applied directly to the ulcer or mixed with Orobase, or betamethasone rinses. Tapuni, et al., demonstrated a significant decrease in the Ulcer Severity Score with oral rinses using 500 microgram betamethasone tablet dissolved in 10 mL of water four times a day for treatment and twice a day to prevent recurrence.¹² Topical antimicrobials are the next step on the ladder. Tetracycline, 250 mg dissolved in 10 mL of water and used as a rinse three times a day decreased pain significantly. Chlorhexidine rinses 0.12% also has demonstrated efficacy. Topical anti-inflammatories, such as diclofenac have been used, as has topical sulcrafate. Topical immunomodulatory agents have been used in recalcitrant cases, such as azelastine and cyclosporine.

If topical treatments are unsuccessful, physical therapies have been used: surgical removal or debridement, laser ablation, low dense ultrasound, chemical cautery (with agents such as silver nitrate), and barriers like cyanoacrylate adhesives.

For severe cases not responding to topical treatments, systemic treatments have been tried, although none are FDA approved. Immune enhancement agents, such as levamisole have been tried. Systemic steroids at doses of 1 mg/kg daily for one to two weeks have been used for severe exacerbations. Systemic cyclosporine and chlorambucil have shown some efficacy.

Agents used for prevention include dapsone, colchicine, pentoxifylline, methotrexate, and thalidomide. Biologic agents such as infliximab or entarecept have also been used.

Pruritis ani

At the other end of the alimentary canal is a less common but just as vexing issue. Pruritis ani (PA) is an intense, irresistible, chronic itching of the perianal region. PA was first mentioned in an ancient Egyptian papyrus in which 10 of the 41 remedies listed were to manage anal itching. It is estimated to affect 1–5% of the population, is four times more common in men, and presents most commonly in the fourth to sixth decade of life.¹³ Most cases have associated pathology, but up to 25% can be idiopathic. Over 100 causes have been reported, and can be dermatologic, hygienic, infectious (including sexually transmitted infections), due to topical or dietary irritants, due to systemic disease including malignancies, or psychological^13,14 (See Table 2). It is beyond the scope of this paper to discuss all causes—instead this paper will focus on the cases often felt to be idiopathic.

Table 2.

ITCH acronym for initial evaluation of causes of pruritis ani

Acronym	Examples
I-infections	Candida albicans, herpes, Condyloma accuminata, HIV, syphilis, gonorrhea, pinworm, other bacteria (erythrasma caused by Corynebacterium minutissimum)
T-topical irritants	Detergents, tight occlusive clothing, nylone undergarments, dyes and scent in toilet tissue
C-cutaneous	Lichen planus, psoriasis, contact dermatitis, seborrhea, lichen sclerosis, lichen simplex chronicus
C-cancer	Paget's, skin cancers, Mycosis fungoides
H-hypersensitivity	Foods ("C's"-coffee, cola, citrus, chocolate, and calcium), medications (colchicine, quinidine, chemotherapy)

Two of the most common causes of PA are related to hygiene—too little or too much. Fecal soiling, whether overt or occult, can lead to local irritation and maceration with resultant itching. Local conditions, such as anal fistulae or hemorrhoids can result in fecal leakage and skin irritation. This is usually detectable on examination and appropriate treatment instituted—resolution of conditions leading to the incontinence if possible, and barrier creams to protect the skin.¹³

Conversely, excessive hygiene can lead to PA. Often this begins with a sign or symptom such as minor itching or stained undergarments the patient relates to inadequate cleansing after bowel movements. As a result, vigorous hygiene with soap is often used to resolve the condition, but the over-zealous hygiene removes the protective mucous layer around the anus. As a result the itching intensifies and more cleansing is used in attempts to resolve it. If the history obtained is suggestive of over-zealous hygiene, resolution of the symptoms usually is rapid with advice to discontinue the cleansing practices—particularly the use of soaps—and application of petrolatum for a few days to allow the condition to resolve.¹⁴

If there is no explanation for the itching with the above conditions, then further history and examination must be done. Henderson, et al. suggest helpful mnemonics: the “Cs” and ITCH. ¹⁵

Food intolerances can cause PA. The most common foods reported are the “Cs”: cola, coffee, chocolate, citrus, and calcium (dairy products). There may be a direct correlation to the symptoms and amount of coffee consumed in sensitive individuals.¹⁶ Elimination diets are effective in these patients, with recurrent symptoms on re-challenge.

The ITCH acronym suggests looking for infections, topical irritants, cutaneous conditions/cancer, and hypersensitivity (See Table 1).

Table 1.

Causes of Pruritis Ani

Dermatologic Conditions	Fecal Soilage	Systemic Disease
Atopic dermatitis	Anal Fissure	Aplastic anemia
Contact dermatitis	Chronic constipation	Diabetes mellitus
Hidradenitis suppurativa	Chronic diarrhea	Inflammatory bowel disease
Lichen planus	Fistula	Jaundice
Lichen sclerosis	Incontinence	Leukemia
Psoriasis	Prolapsed hemorrhoids	Lymphoma
Seborrheic dermatitis	Rectal prolapse	Thyroid Disease
	Skin tags
Infections		Medications
Abscess	Dietary irritants	Chemotherapy
Candida (intertrigo)	Beer	Colchicine
Erythrasma	Coffee	Neomycin
Molluscum contagiosum	Chili peppers	Quinidine
Parasites (pinworms, scabies)	Citrus, tomatoes
Sexually transmitted (e.g., herpes simplex, syphilis, HPV)	Milk
		Topical irritants
		Deodorants
Malignancy	Miscellaneous	Detergents/fabric softeners
Bowen disease	Idiopathic	Soaps
Extra-mammary Paget’s	Lumbosacral radiculopathy	Suppositories
Squamous Cell Carcinoma	Psychological disorders	Talcum powder
		Tight clothing
		Toilet paper dyes and perfume
		Hemorrhoidal remedies

Adapted from Fargo, et al. ¹⁴

A number of systemic diseases have been linked to PA, including diabetes mellitus, uremia, thyroid disease, inflammatory bowel disease, jaundice, leukemia, and lymphoma.¹⁴

Evaluation of a patient with symptoms of PA should include a history to discover potential reversible secondary causes, symptoms of systemic illness, or exposure to irritants, food exposures, or exposures to infections. Examination should include inspection of the perianal region looking for local factors (e.g., hemorrhoids, fistulae, papilloma, condyloma, signs of infection), the presence of lichenification, implying chronicity, and skin changes suggesting an underlying dermatological or pre-malignant condition. A rectal examination is indicated for detection of internal hemorrhoids or masses. An anoscopy should be done if the diagnosis is not apparent from the external examination.¹⁵

Treatment is aimed at elimination of irritants and scratching. Adequate hygiene is imperative, however patients should be admonished to avoid aggressive perianal cleansing that can aggravate the condition and to avoid medicated or scented wipes or soaps after defecation. Instead they should use plain tissue or wipes to cleanse the perianal region. It should be emphasized that keeping the perianal region dry is important. Patient education regarding “pat” drying the perianal region or using a blow dryer on the cool setting may be beneficial.¹⁵

Addressing reversible causes such as hemorrhoids or fistulae or treating infectious causes is necessary, as is elimination of irritants and foods which may be causing the issue. In addition to patient education and treatment of secondary causes, medication may be needed. The itching of PA can be profound, and antihistamines may be helpful in diminishing the pruritis, particularly when used at night. Tricyclic antidepressants such as doxepin can also be helpful for night time itching. Witch hazel has been used as a topical anti-pruritic. Barrier creams can be helpful, such as zinc oxide or petrolatum. Low potency topical steroids, such as hydrocortisone 2.5% can be used for short periods to help with inflammation and itching, but must be used with caution due to the risk of epidermal thinning.¹⁵

Though somewhat counterintuitive, capsaicin cream 0.006% can be effective. The short intense burning produces an inhibitory feedback.¹³ In one randomized study, both 1% hydrocortisone and capsaicin 0.006% worked better than placebo.¹⁷

For the intractable cases, anal tattooing with methylene blue has been used.

Biography

R. Stephen Griffith, MD, MSMA meber since 2011, is Associate Professor, University of Missouri - Kansas City, Department of community of family Medicine and Truman Medical Center-Lakewood.

Contact: Steve.Griffith@tmcmed.org