Lecture 9 - 40s and 50s PDF

Lecture 9 – 40s and 50s Actinic Keratosis (AK) AKs are common lesions. The more lightly pigmented a patient is, the more likely they are to have AKs. Chronic sun exposure, especially in areas of more intense UV (closer to the equator), is the other significant risk factor for AKs. AKs start as ro...

Lecture 9 – 40s and 50s Actinic Keratosis (AK) AKs are common lesions. The more lightly pigmented a patient is, the more likely they are to have AKs. Chronic sun exposure, especially in areas of more intense UV (closer to the equator), is the other significant risk factor for AKs. AKs start as rough patches on sun exposed skin, especially the face. As an AK progresses, it goes from being rough to having thick, adherent scale (Figure 9.1). In addition, the skin under the scale often becomes erythematous (Figure 9.2). The typical AK is 0.5 – 1.5 cm in diameter and has rather ill-defined borders. Most patients with AKs have multiple lesions. AKs are considered to be precursor lesions of cutaneous squamous cell carcinoma (SCC). Between 0.1% and 1% of AKs will develop into SCCs. UV radiation causes the mutations which lead to AK development. The most common mutation is loss of function of p53. AKs are usually treated with destructive means. There are multiple destructive modalities available: freezing with liquid nitrogen, burning with electrocautery, and chemical destruction with topical 5-Fluorouracil. Freezing and burning are useful for treating patients who have few to several lesions. For patients with many lesions, topical 5-Fluorouracil is more appropriate, as multiple lesions can be treated simultaneously. In addition, it is important to counsel patients that the presence of AKs indicates a high risk for developing skin cancer. While AKs only develop into SCCs, they indicate significant sun exposure, and thus identify patients as being at high risk for developing basal cell carcinomas and melanomas. Therefore, patients with a history of an AK should have at least annual skin exams and should use sunscreen on a daily basis. Onychomycosis and Tinea Pedis Onychomycosis and tinea pedis are both extremely common, and both become more common with increasing age. Other risk factors are poor circulation to the lower extremities, diabetes, and immunosuppression. The two diseases are often found simultaneously. Onychomycosis is fungal infection of the toenails. It presents as yellow or white discoloration of the toenails. There is often separation of the nail from the nailbed with significant accumulation of scale and white, powdery material under the nails. The nail may also be quite thickened. The toenails are affected much more commonly than the fingernails (Figure 9.3) (Figure 9.4). Tinea pedis is an extremely common fungal infection of the skin of the feet. There are several types. In the “moccasin” type, redness and dry scaling occurs on the sole and sides of the foot (Figure 9.5) (Figure 9.6). In the interdigital type, there is soggy, white, fissured skin between the toes, most commonly between the 4th and 5th toes (Figure 9.7). Finally, in the bullous type, there are 0.5 – 1.5 cm groups of small blisters on the sole of the foot (Figure 9.8). The moccasin and interdigital types are much more common than the bullous type. When a fingernail with green discoloration separates from the nailbed, it is called “Green nail” (Figure 9.9). It is asymptomatic. The green color is usually quite striking and is most often due to Pseudomonas aeruginosa infection (green pigment production  pyocyanin). Onychomycosis is caused by dermatophytic fungi, most commonly Trichophyton rubrum and Trichophyton mentagrophytes. Dermatophytic fungi produce keratinases, enzymes that break down keratin, allowing the fungi to penetrate keratinized tissue (i.e., nails or stratum corneum). Different types of Tinea pedis are caused by different dermatophytes Moccasin type  Trichophyton rubrum Interdigital type  Trichophyton mentagrophytes var. interdigitale Bullous type  Trichophyton mentagrophytes var. mentagrophytes Systemic agents must be used to cure onychomycosis. The most effective agent is terbinafine, which stays in the nail for months after the medication is stopped. Itraconazole is relatively effective (less than terbinafine), and also stays in the nail for months after it is stopped. Tinea pedis can usually be treated with topical terbinafine BID to the entire foot until better. It is important to note that if a patient has both T pedis and onychomycosis, treatment for T pedis cannot be effective unless the onychomycosis is also treated. The reason is that unless the onychomycosis is also cured, fungus from the infected toenails will spread back onto the skin. Green nail can usually be treated by applying ofloxacin eardrops under the affected nail. Systemic antibiotics are not particularly effective, as they do not reach this site very well. The drops may need to be applied daily for several months. Soaking the finger in a solution of one part vinegar and five parts water for 10-15 minutes a day is also helpful. Sarcoidosis Sarcoid most commonly presents in women between 20 and 60. It is more common in African- American women than in Caucasian women. Cutaneous sarcoidosis presents most commonly as non-inflamed papules and nodules. These lesions are often described as having an “apple-jelly” appearance – yellow-brown and slightly “waxy”. The papules and nodules can vary from 0.2 cm to several centimeters in diameter (Figure 9.10) (Figure 9.11). Sarcoid is considered the “great imitator” in dermatology, as although the papules and nodules described above are the most common finding, the lesions of sarcoid can have almost any appearance. In addition, as mentioned in the previous lecture, erythema nodosum can be associated with pulmonary sarcoidosis. Sarcoid is a multisystem granulomatous disease, primarily affecting the lungs. The cytokine profile of the disease is a Th1-dominant profile, with CD4+ lymphocytes and macrophages dominating the picture. The underlying cause of the disease is unknown. Small numbers of cutaneous lesions can be treated very effectively with intralesional steroid injections. Intralesional injections are not practical for large numbers of lesions, so systemic medications become necessary. Medications that can be effective include anti-inflammatory antibiotics (minocycline), antimalarials (hydroxychloroquine), methotrexate, and prednisone. If cutaneous sarcoid is diagnosed, the patient should have a thorough multi-system exam to look for other involved organs. Most important are a chest x-ray, pulmonary function studies, an EKG, and ophthalmologic exam. Dermatomyositis (DM) DM is most common in women around age 50. It is a relatively rare disease, although the prevalence may be increasing. There are many cutaneous manifestations of DM. The most diagnostic findings are heliotrope and Gottron’s papules. Heliotrope is edema and violet-red color of the eyelids, more commonly of the upper eyelids. Heliotrope is often very subtle and difficult to clearly identify. Gottron’s papules are small (1-5 mm), red, scaly papules on the dorsal aspect of the fingers, overlying the knuckles (Figure 9.12) (Figure 9.13). Other important findings are the shawl and V-neck signs. These are violaceous erythema of the V-portion of the neck (Figure 9.14) and upper back (Figure 9.15). There will often be scaling or crusting and pruritus as well. A similar eruption can also occur on the upper, outer arms, elbows, knees, thighs, and ankles. Gottron’s sign is erythema without papules on the dorsal aspects of the fingers overlying the knuckles. Gottron’s sign is similar to Gottron’s papules without the papules. Finally, patients with DM often have abnormal nail cuticles, ranging from erythema of the skin around the nails to changes of the capillaries in the cuticles. Capillary changes include large, dilated capillaries or disappearance of the capillaries, or most commonly some combination of both (Figure 9.16). In this setting, the cuticles are often described as “ragged” or dystrophic. DM is one of the idiopathic, inflammatory myopathies. It is often induced by “novel” antigens, such as tumors or drugs, but overall, the pathogenesis is essentially unknown. Anti-synthetase antibodies are the most frequent class of antibodies in DM; anti-Jo-1 is the best known. These are serum antibodies directed against tRNA synthetases located in the cytoplasm, so these antibodies are NOT anti-nuclear antibodies. Compared to patients without anti- synthetase antibodies, those with them are more likely to have significant pulmonary disease. Anti-nuclear antibodies are found in approximately half of patients with DM, and they are neither sensitive nor specific for DM. Due to muscle inflammation and damage, muscle-derived enzymes are detectable in the blood (aldolase, CPK, AST, ALT). Only checking AST and ALT would lead one to suspect liver disease; however, if checked, elevated CPK and aldolase will confirm the muscle disease. Some patients have cutaneous manifestations of DM without muscle disease or other systemic involvement. Treatment of these patients revolves around aggressive sun protection and topical steroids. If this is not sufficient, then systemic immunosuppressive medications, such as prednisone, azathioprine, and methotrexate are needed. Patients with systemic disease (pulmonary, muscle) require systemic treatment with the above medications, and if these are not sufficient to control the disease, other medications, such as intravenous immunoglobulin or cyclophosphamide are used. Importantly, all patients over age 40 presenting with DM, regardless of whether or not there is systemic involvement (i.e., even if the disease is limited to the skin), should have an aggressive malignancy work-up. Specifically, colonoscopy, mammogram/prostate exam, CBC (leukemia), urinalysis (for hematuria), and CT scan of chest/abdomen/pelvis (ovarian carcinoma, lymphoma, lung carcinoma, gastric carcinoma). This aggressive evaluation is necessary because ~20% of patients with DM over age 40 have an underlying malignancy, the most common being ovarian carcinoma. The malignancy may be detectable at the time of diagnosis of DM or may not become detectable for up to 3 years after DM starts. Therefore, if the above evaluation is negative at the time of diagnosis, it should be repeated yearly for the first three years. The likelihood of malignancy increases with increasing age, but in patients under 40, it is probably still worthwhile to pursue a malignancy work-up, unless the patient is under age 18, in which case, there is no association with malignancy. Systemic Sclerosis (SSc) SSc is an uncommon disease, seen almost exclusively in women, with onset between the ages of 30 and 50. SSc is divided into limited and diffuse forms. The major difference is that in the limited form, the skin of the trunk and proximal extremities is spared, with thickening limited to the distal extremities (Figure 9.17) and face. In the diffuse form, the proximal extremities and trunk are involved, in addition to the hands, feet and face. In both forms, there are typical findings in addition to the skin thickening. Microstomia, or decreased oral aperture, is a result of sclerosis of the facial skin. Telangiectasias are frequently very prominent on the face (Figure 9.18). There are often skin ulcerations (Figure 9.19) and calcifications on the fingers (Figure 9.20). The capillaries of the nail cuticle are often abnormal, similar to that seen in dermatomyositis (some capillaries enlarged, some missing). Raynaud’s phenomenon typically precedes the onset of the disease. A subset of limited SSc is the CREST syndrome. In CREST syndrome, there is accentuated calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. These finding are also present in regular limited SSc and diffuse SSc, but are quite prominent in CREST. Also, in CREST, the other manifestations of the disease (thickening of skin other than on the fingers, systemic involvement) are not well developed. Common systemic involvement includes swallowing difficulty from esophageal dysmotility, constipation from intestinal dysmotility, pulmonary hypertension, and renal crisis leading to renal failure and severe hypertension. SSc is considered an autoimmune disease, but the pathogenesis is very poorly understood. There is a clear increase in dermal collagen production in involved skin. It is thought that TGF-beta is involved in causing the up-regulation of collagen production. An interesting theory is that scleroderma may be related to graft-versus-host disease. It is thought that microchimerism may develop from the placenta during pregnancy, and this presence of “foreign” cells may stimulate an immune response, leading to the increased collagen production. Several auto-antibodies are present in SSc. Specifically, anti-centromere antibodies are associated with CREST syndrome, and anti-scl70 antibodies are associated with diffuse SSc. Anti-scl70 antibodies are directed against topoisomerase I. Most patients have anti-nuclear antibodies, regardless of the presence of anti-scl70 or anti-centromere. SSc is extremely difficult to treat and requires systemic immunosuppressants. Renal disease can be prevented with ACE inhibitors, and this has dramatically improved the prognosis of the SSc in general. Pulmonary hypertension is difficult to treat, but prostacyclin infusions have shown some benefit. Patients with esophageal dysmotility should be on proton pump inhibitors. There is some evidence that d-penicillamine, an immunosuppressive that inhibits collagen production, can improve the skin disease. Burning vulva syndrome, burning scalp syndrome, burning mouth syndrome Each of these diseases is relatively uncommon, but not rare. They are all seen most commonly in peri-menopausal and post-menopausal women. These diseases fall into the category of cutaneous dysesthesia syndromes. By definition, there is no identifiable physical cause, and physical examination is normal. The three diseases do not occur together in a given patient, but they will be discussed as a group, since they have similar presentations, only at different anatomical sites. Patients complain of burning or pain, but not of itch. The symptoms can be continuous, randomly intermittent, or may recur at specific times or with specific activities. The pathophysiology of these diseases is currently not understood. The most viable hypothesis is that they represent abnormal function of the cutaneous or mucosal sensory nerves, and therefore are a type of neuropathy. There is a clear relationship between the dermatologic symptoms and a triad of stress, anxiety, and depression (SAD triad). This is not to say that the symptoms are a result of the SAD triad. It is more likely that the SAD triad leads to an alteration of central regulation of peripheral nerve function. In addition, the pain and burning certainly cause the SAD triad, and thus, an escalating cycle of burning symptoms and psychologic dysfunction can be present. The initial step in evaluating patients with these symptoms is to rule out identifiable causes, such as dry mouth, Sjogren’s syndrome, decreased vaginal secretions, candidiasis, contact dermatitis, lichen planus, etc. This typically means performing a good physical examination and taking swabs for candidal and bacterial cultures. In patients with burning mouth syndrome, iron, folate, B12, B1, B2, and B6 levels should be checked, as a vitamin deficiency can cause burning mouth symptoms. Also, referral to the relevant specialist (ob/gyn, dermatologist, dentist) is appropriate. If underlying causes have been ruled out, then treatment should be directed at abnormal nerve function. This typically means using medications such as gabapentin, pregabalin, imipramine, and amitriptyline. These medications typically help alleviate the symptoms. However, it is unusual for the symptoms to resolve completely. Generalized Pruritus, Pruritus of Unknown Origin, Pruritus without a rash Generalized pruritus is uncommon. It can affect individuals of any age or race. By definition, patients with generalized pruritus experience widespread, symmetrical itch. Their entire body does not have to itch, but the itch does have to affect large areas. In addition, there cannot be any rash associated with the pruritus (other than sequelae of scratching). Specifically, it is very important to look for xerosis (dry skin) and signs of scabies (mite infestation). Originally, pruritus was thought to be equivalent to “low grade pain” from a neurophysiologic perspective. Data has shown this view to be incorrect. There are specific “itch receptors”, specific nerve fibers that transmit itch, and CNS regulatory centers that affect itch perception. Opioids are some of the stronger CNS itch mediators, and we often see patients on narcotic medications who complain of itch. The first step in treating generalized pruritus is to look for an underlying cause, as about 15-20% of patients will have a systemic cause of their itch. Causes include renal failure, iron deficiency- anemia, hyperbilirubinemia, other types of liver disease (hepatitis B, C), hyper- or hypo- thyroidism, and cancer. Hematologic malignancies (leukemia, non-Hodgkin’s lymphoma, and Hodgkin’s Disease) are the most common cancers, but rare reports of generalized pruritus exist for all types of solid malignancies. All patients with generalized pruritus should have the following bloodwork and films: CBC with differential Total bilirubin BUN/Creatinine ALT/AST TSH Alkaline Phosphatase Hep B panel Chest x-ray Hep C antibody If, based on the H&P, there is high suspicion for malignancy, then a CT scan of the chest, abdomen, and pelvis should be considered. The underlying cause, if identified, should be treated. However, if no underlying cause is identified, then treatment is directed at trying to relieve the pruritus with topical agents, such as steroids, menthol, and camphor. Antihistamines are also usually useful. Non-sedating antihistamines (loratadine, fexofenadine, cetirizine) are used during the day, and sedating antihistamines (hydroxyzine, diphenhydramine, doxepin) are used at night. In recalcitrant cases, agents such as gabapentin, naloxone (an opioid blocker), and paroxetine are sometimes effective. Contact Dermatitis Contact dermatitis is extremely common. It is one of the most common reasons for seeing a dermatologist. The two types of contact dermatitis are allergic and irritant. The classic cause of acute allergic contact dermatitis is poison ivy. Most individuals in the US are sensitized to this plant, and when they come into contact with it, they develop a red, bullous, intensely pruritic eruption (Figure 9.21) anywhere from 8 hours to 3 days later. The eruption lasts for approximately 3 weeks. Chronic allergic contact dermatitis is also very common. While over 3000 separate agents that cause allergic contact dermatitis have been reported, there are only a few common causes: Nickel: Nickel is the most common cause of chronic allergic contact dermatitis. It is found in most jewelry (except 24kt gold) (Figure 9.22), belt buckles (Figure 9.23), and clothing snaps and buttons. On a population basis, prevalence of nickel allergy is directly related to prevalence of ear piercing. Nickel allergy is usually easily self-diagnosed by patients. Preservatives and fragrances: Common exposures are personal care products (soap, shampoo, moisturizer) and cosmetics (make-up, nail polish, perfume (Figure 9.24)). Allergy to preservatives and fragrances can be extremely difficult to diagnose, as many agents cross- react, and many agents are used in multiple different products. Thus, a patient may suspect they are allergic to a moisturizer, and switch to a different product, but if the causative ingredient is in both products, they will not get better.  Topical medications: By far the most common topical medication allergies are to neomycin and bacitracin. Neomycin is in Neosporin and “triple antibiotic creams”, and bacitracin is in Neosporin, Polysporin, and “double antibiotic creams”. These are also often difficult to diagnose, as patients will apply the medication to treat a minor abrasion (Figure 9.25) or cut, and when an allergic reaction develops, they think the wound has become infected. This same scenario can occur if Neosporin is used post-operatively to treat surgical sites. The other type of contact dermatitis is irritant contact dermatitis (ICD). Any agent that can damage the skin can cause ICD. In general, the more toxic the agent, the shorter the duration of contact necessary to cause a reaction. Chemical burns (i.e., from acids) are a good example of this type of acute irritant contact dermatitis. Chronic ICD is much more common than acute ICD. The most common site of chronic irritant dermatitis is the hands, and this is discussed in more detail in lecture 12. Allergic contact dermatitis is a type 4 hypersensitivity reaction, mediated by lymphocytes with a Th1 cytokine profile (IL-2, IL-12, Interferon gamma). On first exposure to an antigen, there is no clinical reaction, instead the antigen is transported to the regional lymph nodes in antigen presenting cells, and memory lymphocytes are produced. On re-exposure to the antigen, the memory lymphocytes traffic to the site of exposure and react to antigen being presented at that site by antigen presenting cells. In general, allergens act as haptens, binding to protein, and the allergen–protein complex acts as the antigenic agent. Most allergens are non-protein, small molecules, less than 500 daltons in molecular weight. Treatment of allergic contact dermatitis revolves around identifying the causative agent and avoiding exposure to it. This can be relatively easy, as with nickel dermatitis and neomycin allergy, or it can be very difficult, as with allergies to fragrances and preservatives. Avoiding fragrances is especially difficult because products labeled and “unscented” or “fragrance-free” often contain fragrance. When allergic contact dermatitis is suspected, a patch test should be performed. Patch testing is done by dermatologists who specialize in diagnosing allergic contact dermatitis. In this test, pure allergens are applied to the patient’s back under occlusion for two days. After two days, the allergens are removed, and the following day, the skin is examined. A positive test manifests as redness and erythema of the skin at the site where the allergen was applied. Since the causative allergen is often unknown, up to 150 allergens may be applied to the back of a given patient. In addition to avoiding the relevant allergen, symptomatic relief can be accomplished with topical or systemic steroids. However, steroids are not a good long-term treatment, as they often lose effectiveness and can cause side effects when used long term. In irritant contact dermatitis, the diagnosis is either apparent based on history and physical, or the diagnosis is one of exclusion, meaning that if patch testing is negative, we then consider the patient to have irritant contact dermatitis. In irritant contact dermatitis, the patient must protect the skin from injury with gloves or protective clothing. If this is not possible, the patient must minimize the effects of the relevant irritant, usually with lipid-rich moisturizers.