Lecture 8 Part 2 PDF

Rosacea Rosacea is very common in lightly pigmented individuals, especially those of Irish or Scottish descent. Rosacea often begins with intermittent flushing. Triggers, such as hot drinks, alcohol, caffeine, hot food, spicy food, wind, or sunlight, immediately cause a sensation of facial warmth,...

Rosacea Rosacea is very common in lightly pigmented individuals, especially those of Irish or Scottish descent. Rosacea often begins with intermittent flushing. Triggers, such as hot drinks, alcohol, caffeine, hot food, spicy food, wind, or sunlight, immediately cause a sensation of facial warmth, and the central facial skin turns red. Eventually, this redness may become permanent, and the patient may develop facial telangiectasias. (Figure 8.12) The next phase of rosacea may occur after the flushing and redness have been established, may start at the same time as flushing and redness, or may happen in the absence of flushing and redness. In this phase, there are red papules and pustules, mainly distributed along the cheeks, but also found on the nose and forehead. (Figure 8.13) The third major type of rosacea typically occurs after years of one or both of the above. In this type, there is slow thickening of the skin of the nose, which can become dramatically enlarged. This is called rhinophyma. (Figure 8.14) Rosacea is poorly understood. There is clearly a component of hyperresponsiveness of the face’s cutaneous vasculature. One theory is that this excess vasodilatation of the cutaneous vessels leads to edema and inflammation of the skin. It is important to note that if a papule or pustule is biopsied, the inflammation is centered on a follicle. Rosacea is mainly treated with topical antibiotics, such as metronidazole and clindamycin. These antibiotics are effective for treating papules and pustules, but they are not effective for treating general erythema, flushing, or rhinophyma. In this disease, the antibiotics are thought work because of their anti-inflammatory effects, not because they are killing any microbes. For more severe cases, oral antibiotics, such as doxycycline are used, again, working more as anti- inflammatory agents, not anti-microbial agents. For individuals whose main problem is flushing, the most effective approach is to identify triggers and then try to avoid them. For individuals who are mainly troubled by general erythema of the skin or telangiectasias, treatment with pulsed dye laser is most effective. This laser specifically targets hemoglobin and leads to destruction of superficial blood vessels, thereby decreasing erythema. For rhinophyma patients, surgical removal of excess skin on the nose is the only significantly effective treatment. Livedo Reticularis (LR) LR is a fairly common physical exam finding. It is more common in women. LR presents as a bluish to violet, net-like pattern on the skin, usually on the legs (Figure 8.15). There is no palpable component, and there are usually not any symptoms. It is most commonly caused by skin exposure to cold temperature, and thus should resolve with temperature increases. In some cases, LR can be persistent and unrelated to cold exposure, and in these cases there can be an “aching” of the skin. In this setting, a good review of systems should be undertaken, and the patient should be questioned about a family history of blood clots. LR represents an excess of de-oxygenated blood in the small venules of the cutaneous plexus, which we are then able to see through the skin. Any process that increases the amount of blood or decreases the amount of oxygen in the venules can lead to LR. In typical cold-related LR, the cold leads to arterial vasoconstriction and slower flow of blood through the skin. More oxygen is extracted from the slower flowing blood, leading to greater de- oxygenation, thus increasing the visibility of the blood in the venules. In persistent LR, there are many potential causes. Any cause of increased blood viscosity, such as a lupus anticoagulant or cryoglobulinemia, can lead to slower flow through the cutaneous vessels, and thus cause LR. Alternatively, any cause of vasodilation of the cutaneous venules, such as neurologic or endocrine disorders, can also cause LR. Finally, any cause of arteriolar vasoconstriction, again from causes like neurologic or endocrine disorders, can cause LR. In typical cold-related LR, which is by far the most common type, no treatment is necessary. As noted above, if LR is persistent and does not disappear with skin warming, the patient should be evaluated for underlying causes. This typically means performing a good review of systems and general physical exam. There is a known connection between LR and lupus anticoagulant in women, and thus, should be checked in any woman who presents with persistent LR. Raynaud’s phenomenon Raynaud’s phenomenon is a relatively common disorder in young women. It is less common in men. There may be a weak association between Raynaud’s and migraine headaches. Raynaud’s phenomenon is a vasospastic disorder affecting the hands. Most commonly, on exposure to cold, several or all fingers will turn either blue or white. This color change is often associated with some numbness or tingling. After a variable amount of time, the affected areas turn bright red and may swell slightly, often with an accompanying burning or aching sensation. The classic description of Raynaud’s includes three phases: white, then blue, then red. As noted above, most patients report only two phases: white then red, or blue then red. Severe Raynaud’s may be associated with gangrene or ulceration of affected skin. There are several possible causes of Raynaud’s phenomenon. It may be a disorder of the sympathetic nervous system’s control of the digital vessels. It may be due to hyperviscosity of the blood. It may be due to an anatomic or functional abnormality of the digital vessels themselves. Finally, it may be due to local overproduction of a vasoconstrictor or local underproduction of a vasodilator. The first step in treating Raynaud’s is to determine if it is primary or secondary. Primary Raynaud’s phenomenon (80-90%) is Raynaud’s with no underlying associated disease. Secondary Raynaud’s is Raynaud’s caused by an underlying disease. By far the most common causes of secondary Raynaud’s are connective tissue diseases, especially diffuse and limited systemic sclerosis. Arterial obstructive disease, neurologic disorders, and hypercoaguable/ hyperviscosity diseases are much less common causes. Some patients may present with primary Raynaud’s, and may then develop diffuse or limited systemic sclerosis years later. For this reason, even if no underlying disease is identified initially, you must continue to follow patients. In a patient presenting with Raynaud’s, in addition to a review of systems and general examination, it is worthwhile to check an ANA and possibly an ESR. On physical exam, it is important to look carefully for any signs of skin tightening and to look for abnormalities of the capillaries of the proximal nail folds, as these can be early signs of systemic sclerosis. Treatment of Raynaud’s phenomenon centers on trying to keep the extremities warm. If this is not sufficient, then therapy with calcium channel blockers, such as nifedipine or diltiazem is usually effective. Therapy is more likely to be effective in primary than in secondary Raynaud’s. Pemphigus Vulgaris (PV) and Pemphigus Foliaceous (PF) PV is a rare auto-immune blistering disease with onset commonly in the 30s, 40s, or 50s. There is no gender bias, but it is more common in individuals of Jewish or Mediterranean descent. PV is a severe, life threatening autoimmune disorder, presenting with painful blisters and oral (Figure 8.16) and cutaneous (Figure 8.17) (Figure 8.18) erosions. Some patients have only oral involvement, but most have both oral and cutaneous involvement. Patients with only cutaneous involvement are more likely to have a related disorder, called Pemphigus Foliaceous, which is more likely to affect elderly patients than is PV. Blisters in these diseases are usually fragile, flaccid, and large. The erosions actually represent ruptured blisters. The disease has a spectrum from mild to severe. Mild cases may have only occasional oral erosions and a few small blisters on the skin. In severe cases, the entire oral and esophageal mucosa can slough, and the entire cutaneous surface can be covered with blisters and erosions. Pemphigus vulgaris is more common and more severe than pemphigus foliaceous. A specific immune response develops against desmoglein proteins in the epidermis in both diseases. The immune response results in production of IgG, which binds desmoglein preventing it from performing its function, which is to hold the epidermis together. In PV, the immune response is directed against desmoglein 3 (oral disease only) or both desmoglein 3 and desmoglein 1 (oral and cutaneous disease). In PF, the immune response is directed against desmoglein 1 (cutaneous disease only). Desmoglein 1 is expressed throughout the stratum spinosum of the epidermis and to a very small degree in the mouth. Desmoglein 3 is expressed throughout the oral epithelium, mainly in the deeper parts of the stratum spinosum. These expression patterns explain why disease is limited to the skin when only desmoglein 1 is affected, the disease is limited to the mouth when only desmoglein 3 is affected, and the disease affects mouth and skin when both are affected. The blisters in these diseases are fragile because they are intraepidermal blisters. We will later discuss another autoimmune blistering disease in which the blisters are much less fragile because they are subepidermal blisters. Pemphigus is treated with immunosuppressive medications. Prednisone is the most effective medication, but the long-term side effect profile prevents its chronic use. Therefore, other medications with better long-term safety profiles, such as azathioprine, mycophenalate mofetil, and cyclophosphamide, are used in order to decrease the need for prednisone. In resistant cases, intravenous immunoglobulin and/or plasmapheresis are used. The goal of each of these therapies is either to remove the pathogenic antibodies or stop production of the pathogenic antibodies. Cutaneous Lupus Lupus is a systemic autoimmune disease. It is much more common in women. Cutaneous lupus can be seen in patients with or without systemic lupus. There are three types of cutaneous lupus: Acute cutaneous lupus erythematosus (ACLE) Subacute cutaneous lupus erythematosus (SCLE) Chronic cutaneous lupus erythematosus (CCLE) ACLE is seen almost exclusively in patients with systemic lupus erythematosus. It typically presents as the classic malar rash – with erythema and edema of the skin of the cheeks and nasal bridge. The nasolabial folds are typically spared. (Figure 8.19) 50% of patients with SCLE have systemic lupus, while the other 50% have cutaneous lupus with no systemic disease. SCLE presents with a widespread, erythematous, scaly, photo-distributed rash that often spares the face. It is usually not very itchy. (Figure 8.20) (Figure 8.21) 5 – 20% of patients with CCLE (a.k.a. discoid lupus) have systemic lupus. Patients with CCLE who have systemic lupus usually have relatively mild systemic lupus. CCLE presents with 1-3 cm lesions that show atrophy of the epidermis, dilated pores, scaling, and hypo- or hyper- pigmentation. (Figure 8.22) (Figure 8.23) The conchal bowl of the ear is frequently involved, usually showing dyspigmentation. (Figure 8.24) Lupus is an autoimmune disease with both humoral and cell-mediated immune responses against auto-antigens. The photo-related nature of cutaneous lupus lesions is thought to be due to the effects of sunlight on cutaneous cells. The sunlight damages cells, and as part of the effects of this damage, antigens that are typically intracellular and therefore not visible to the immune system, are either released from damaged cells or are expressed on the surface of damaged cells, making them available to the immune system. UVB is more damaging to cutaneous cells, and this is probably the reason why cutaneous lupus is induced more effectively by UVB than by UVA. In patients with systemic lupus, treatment of the systemic lupus with systemic steroids, anti- malarial drugs, and immunosuppressants typically leads to improvement of the cutaneous lupus. However, even in this setting, if the patient does not practice effective sun protection (clothing, UV window filters, sunblock) their cutaneous lupus is likely to flare frequently, which can initiate flares of systemic lupus. In patients with only cutaneous lupus, conservative therapy for mild disease includes aggressive sun protection and use of high potency topical steroids. For patients with more severe disease, anti-malarial agents (hydroxychloroquine and quinacrine) are extremely effective, as long as they are combined with effective sun protection. Polymorphous Light Eruption (PMLE) PMLE is somewhat more common in women. Overall, it is a relatively common disorder (up to 25% of the population), but is usually mild and self-resolving, and therefore, rarely comes to medical attention. It is much more common in “temperate” regions, defined as places where there is a warm, sunny summer and a cold, snowy winter (like Pittsburgh). PMLE presents as erythematous, edematous papules and plaques without scale, usually on the upper chest (Figure 8.25), arms (Figure 8.26), and upper back. It starts in the spring and gets less severe as summer gets closer, until it finally disappears, only to re-appear the following year. PMLE typically spares areas that either do not get a lot of sunlight early in the year (feet, thighs, abdomen) or get lots of sunlight year-round (face, hands). It tends to involve areas that are covered during the winter and exposed during the spring (forearms, upper chest). The pathogenesis of PMLE is uncertain. It is clearly an abnormal response to ultraviolet light, and is probably auto-immune in some sense, as biopsies show infiltrates of lymphocytes into the affected skin. However, the mechanism by which ultraviolet light causes PMLE, the reason for its predisposition for intermittently exposed areas, and the reason it resolves spontaneously with continued UV exposure are all unknown. PMLE can be treated with anti-malarial medications, similar to lupus. Interestingly, it can also be treated by giving people multiple, very low intensity UV exposures early each spring. We think this UV treatment “hardens” the skin, but since the exposures are so low intensity, the treatments do not elicit the clinical disease. Porphyria Cutanea Tarda (PCT) PCT is uncommon but not rare (in other words, you will see patients with this disease). It is more common in men, and typical onset is in the 40s. PCT involves sun exposed skin. Involvement is limited to the skin; there are no neurovisceral symptoms, as are seen in acute intermittent porphyria. Cutaneous findings include skin fragility, blisters, scarring, and milia on the dorsal hands and forearms (Figure 8.27) (Figure 8.28). Fragility includes easy bruising and easy tearing of the epidermis. Facial hyperpigmentation and hypertrichosis (excess hair growth) on the cheeks are often seen. There can be a burning sensation of the skin of the dorsal hands, but most patients are asymptomatic except for painful erosions and ulcers that develop at sites of minor trauma. PCT is caused by a deficiency of the enzyme uroporphyrinogen decarboxylase (UROD). Deficiency of the enzyme leads to accumulation of uroporphyrins, which cause cutaneous damage after absorbing ultraviolet radiation. UROD is mainly present in the liver. Most patients with PCT have chronic liver damage, and this chronic damage leads to decreased UROD activity. The types of liver disease that are common include hemochromatosis, alcoholism, and hepatitis C. In addition, some patients have a genetic deficiency of UROD, which may be severe enough to cause PCT in the absence of liver disease, but which more commonly is a partial deficiency that only manifests clinically when combined with chronic liver disease. UROD is one of the enzymes in the heme biosynthetic pathway. There are multiple other enzymes, and deficiencies in other enzymes of the pathway lead to other types of porphyria. PCT is diagnosed by checking urinary porphyrin levels. Skin biopsy can also be helpful. The most effective treatment for PCT is phlebotomy. Essentially, one unit of blood is removed weekly or biweekly until the hematocrit is 30 and/or symptoms resolve. Phlebotomy is probably effective because it increases the need for heme; thus, fewer precursors accumulate, because patients have only a partial, not complete, deficiency of UROD. In patients with PCT, there is a high prevalence of hemochromatosis, hepatitis C, alcoholism, and HIV. Therefore, patients should be screened for hemochromatosis, hepatitis C and alcoholism, and HIV risk factors should be reviewed. Erythema Nodosum (EN) EN is a relatively common disorder. It is more common in women, and the most common ages are the 20s, 30s, and 40s. EN is the most common type of panniculitis. Panniculitides are diseases in which the primary problem is inflammation in the subcutaneous fat. EN presents with extremely painful, deep seated, red nodules on the shins (Figure 8.29). Most commonly, several nodules develop rather quickly, persist for several weeks, and then resolve. They may recur. Patients may have fevers, chills, or malaise. EN is frequently associated with systemic disorders, such as sarcoidosis, strep infection, coccidiomycosis, viral infections, inflammatory bowel disease, and medications such as oral contraceptives and sulfas. EN is commonly associated with pregnancy. Most often, however, there is no identifiable cause of EN. The etiology of EN is unknown. It is theorized that it represents a hypersensitivity response to circulating antigens, but the exact pathogenesis is unknown. Initial treatment of EN is with non-steroidal anti-inflammatory medications, elevation of the affected legs, and rest. An in-depth review of systems should be performed, and any abnormalities should lead to appropriate testing. In all cases, it is worthwhile to consider checking a chest x-ray and anti-streptolysin antibody. In patients in whom an underlying disease is found, treatment of that disease often leads to improvement of the EN. In patients without an identifiable, underlying cause, initial treatment is as noted above (NSAIDS, elevation, rest). If this is not effective, a short course of systemic steroids is a reliable choice.