Lecture 11 - Miscellaneous Dermatoses PDF

Lecture 11 – Miscellaneous Dermatoses Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)/Polymorphic Eruption of Pregnancy (PMEP) PUPPP/PMEP is the most common dermatosis specific to pregnancy, occurring in 0.5-1% of first pregnancies. It is extremely uncommon after the first pregnancy....

Lecture 11 – Miscellaneous Dermatoses Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)/Polymorphic Eruption of Pregnancy (PMEP) PUPPP/PMEP is the most common dermatosis specific to pregnancy, occurring in 0.5-1% of first pregnancies. It is extremely uncommon after the first pregnancy. The incidence of PUPPP increases with increasing maternal weight gain, being especially common in women bearing twins. It occurs almost exclusively in the late third trimester. Classically, the eruption begins in abdominal striae that develop during pregnancy. It may then become widespread, but the umbilicus is spared (Figure 11.1). The rash consists of erythematous, edematous papules and plaques. In severe cases, there may be tiny vesicles in the papules and plaques. It is extremely pruritic. The pathogenesis of PUPPP is unknown, but the most widely accepted hypothesis is that stretching of the skin leads to exposure of an antigen or antigens that are typically hidden from the immune system. A reaction to this antigen ensues, and it doesn’t remit until the stretching resolves and the antigen(s) become hidden again. Topical steroids and oral antihistamines, such as Benadryl, are often effective for ameliorating itch. In severe cases, oral steroids can be effective. The symptoms and rash always resolves within 1-2 weeks of delivery, so management should be conservative while waiting for spontaneous resolution. Pemphigoid Gestationis (PG) PG is much less common than PUPPP. It also typically occurs late in pregnancy. PG classically starts in the umbilicus (Figure 11.2). Lesions start as red papules and plaques and often develop into tense blisters that may become widespread. It almost always recurs with subsequent pregnancies. In PG, autoantibodies develop against the same antigens as in bullous pemphigoid. Similar to PUPPP, it is thought that antigens not typically available to the immune system become exposed during pregnancy. It is unknown if patients with PG have an increased risk of developing bullous pemphigoid later in life. PG is associated with an increased risk of premature delivery and low-for-gestational-age birthweight. However, there is no documented increased risk of fetal mortality or long term morbidity. In severe cases which require treatment for symptomatic relief, systemic corticosteroids are necessary. There is no evidence that systemic corticosteroids decrease the risk of premature delivery or small-for-gestational-age birthweights. In milder cases, oral antihistamines and topical steroids can be used, but they usually are not effective. Lichen Planus (LP) LP is uncommon, affecting less than 1% of the population. There is no racial predilection. It most commonly occurs in middle-aged individuals, but can affect the elderly and children. Classic LP is described as the “5P” disease: pruritic, purple, planar, polygonal papules. In other words, the classic lesions are small (2-10 mm), itchy, bumps with flat tops and straight angulated borders (Figure 11.3). Fine white lines in a net-like pattern are often seen on the surface of the papules. These are called Wickham’s striae (Figure 11.4). LP most commonly involves the flexor wrists. Other relatively common areas include the forearms, shins, and sacral areas. In addition to cutaneous LP, there is also oral/genital LP. Oral LP most commonly presents as red patches with white lines in a net-like pattern (Figure 11.5) on the bilateral cheeks. A given patient may have isolated cutaneous disease, isolated oral disease, or both. Lichen planus can also involve the lining of the esophagus and the vaginal/genital epithelium. LP is an autoimmune disease with an unknown trigger, possibly a virus, but this is controversial. Lymphocytes, predominantly CD8+ T-cells, attack the epidermis. The clinical manifestations are the result of the damage to and reparative efforts of the epidermis. Cutaneous LP is treated primarily with high potency topical steroids in an effort to locally blunt the activity of the immune system. For severe cases or cases resistant to topical steroids, treatment can be undertaken with systemic immunosuppressive agents or ultraviolet light. Oral LP is also treated primarily with topical steroids. If the disease is progressive, systemic immunosuppressive agents can be given. Granuloma Annulare (GA) GA is a relatively common dermatosis, most common in young adult to middle aged females. GA presents as yellow-to-orange, raised rings (Figure 11.6). It typically does not itch, and there is no scale. The borders of the rings are slightly raised and are somewhat shiny. The backs of the hands are the most common areas involved (Figure 11.7). In rare cases, there can be involvement of large areas of the body. The pathogenesis of GA is completely unknown. Biopsies show granulomas and mucin. GA is asymptomatic, does not affect the health of the patient, and often resolves spontaneously. For persistent cases, attempts to treat with topical steroids are usually not effective. For unknown reasons, trauma to lesions often leads to resolution, so cryotherapy with liquid nitrogen can be tried. If neither above treatment is effective, then oral medications (hydroxychloroquine, dapsone) can be tried, if the patient is willing to accept the risk associated with oral medications. Pretibial Myxedema (PM) Pretibial myxedema occurs mainly in patients with Graves’ disease, although it occurs in less than 5% of patients with Graves’ disease. PM presents most commonly as shiny, indurated nodules or plaques on the shins (Figure 11.8). It is usually symmetric, but not always (Figure 11.9). It may be skin colored, red, or brown. It may be tender, but this is uncommon. PM is an accumulation of mucin in the dermis. The mucin is produced by dermal fibroblasts. It is unclear what causes the fibroblasts to produce the excess mucin, as hyperthyroidism alone does not cause excess mucin production and rare patients without Graves’ disease develop PM. There is no effective treatment. Thyroid disease should be treated, but this does not affect the PM. In fact, patients may develop PM years after their Graves’ disease has been treated. Lichen Simplex Chronicus (LSC) LSC is common in patients with atopic dermatitis. Other pruritic dermatoses may also be complicated by LSC. LSC presents as hyperpigmented plaques of thickened skin. There is significant accentuation of the skin lines (Figure 11.10). There is often mild scaling on the surface, and there may be fissures with small amounts of bleeding. LSC develops as a direct result of chronic scratching or rubbing of a given area. With repetitive, low-grade trauma, the epidermis becomes hypertrophied, giving the lesions their thickened appearance. In addition, lesional skin shows greater than normal numbers of small cutaneous nerve twigs. These nerve twigs make lesional skin more sensitive than normal skin and increase the pleasurable sensation associated with scratching. A cycle is thus developed. Pruritus leads to scratching, which leads to LSC, which leads to increasing pruritus. Continued scratching worsens LSC. This is termed the “itch-scratch” cycle. The key to treating LSC is breaking the cycle. Typically, treatment is twofold: 1) high potency topical steroids, and 2) preventing scratching by covering the lesions with tape, clothing, bandages, or wraps. Oral anti-pruritics, such as doxepin (anti-pruritic tricyclic antidepressant), can be useful additions to treatment. Prurigo Nodularis Prurigo nodules are most common in middle-aged to elderly females, although they can be seen in patients of any age or gender. Prurigo nodularis presents as well-circumscribed, hyperpigmented, hyperkeratotic nodules. There may be one lesion (Figure 11.11) or there may be hundreds of lesions (Figure 11.12). They are most common on the extensor extremities, chest, lower back, and buttocks. They typically spare the face and the central upper back. When a careful history is taken, the patient will state that each nodule starts as an area of normal appearing skin that becomes itchy. The nodule only starts developing after they start scratching the itchy area. This is an important distinction, because if the lesion starts as a “red bump” prior to scratching, prurigo nodularis is not the correct primary diagnosis – there are many other possible primary diagnoses in this case (bug bites, folliculitis, pemphigoid, allergic contact dermatitis, etc.), but prurigo nodularis is only a secondary diagnosis, meaning it happens as a result of the primary diagnosis. Prurigo nodularis is pathophysiologically similar to LSC with hypertrophy of the cutaneous nerve twigs. Prurigo probably represents a form of cutaneous “neuropathy” where a lesion starts when a single nerve twig transmits abnormal “itch” sensation (similar to true neuropathy, where abnormal nerve function leads to transmission of abnormal pain sensation). In response to the itch sensation, the patient scratches, and the scratching leads to increased neural activity and sensitivity, setting up a cycle similar to that of LSC. Eventually, the scratching leads to dermal scarring and epidermal hypertrophy, eventuating in the typical appearance of a prurigo nodule. Prurigo nodularis is difficult to treat. Topical or intralesional steroids may be of some benefit. The most success occurs when it is treated as a neuropathy, with agents like gabapentin, tricyclic antidepressants, or SSRIs. Also, if a patient reports that normal-appearing skin also itches in addition to the nodules, then the full work-up for generalized pruritus should be considered. Irritant Hand Dermatitis (IHD) IHD is common in anyone who washes their hands frequently and/or wears rubber gloves for long periods of time. It is especially common in medical personnel and food service workers. It can be a sign of obsessive-compulsive disorder. IHD presents as erythema and scale of the dorsal hands, palms, and interdigital spaces. There may be associated itch, but a more common symptom is burning/stinging on exposure to water. The dorsal hands and interdigital spaces are usually more affected than the palms, but severe cases can have diffuse involvement (Figure 11.13) (Figure 11.14). The stratum corneum is responsible for protecting the skin from irritants. The oil layer generated by the sebaceous glands and keratinocytes is extremely important for this function. Soap is extremely effective at removing this oil layer, and if the hands are washed frequently enough, the removal of oil can eventually outpace the skin’s ability to recreate the oil layer. Once this happens, the skin becomes susceptible to irritants. Common irritants include water, soap, and foods. This sequence of events leads to “chronic irritant dermatitis”. The other type of irritant hand dermatitis is acute IHD. In this variant, a strong irritant, such as acid or alkali, contacts the hands. These strong irritants are able to overcome the barrier of the stratum corneum immediately and cause immediate significant damage to the skin. Ideally, irritant hand dermatitis is treated by decreasing the frequency of hand exposure to water. This can be accomplished sometimes by changing habits or jobs. If this is not possible and there is still exposure to water, then decreased exposure should be pursued by encouraging patients to wear rubber gloves over cotton liners when the hands are exposed to water. In addition, it is important to apply a moisturizer as frequently as possible (ideally after every exposure to water). Initially, topical steroids can be used to relieve symptoms quickly, but topical steroids impair healing when used chronically. In terms of helping a patient choose a moisturizer, as a general rule, the thicker the moisturizer is, the better it will work. Acute Urticaria Acute urticaria is most common in children and young adults. Acute urticaria presents as blanched papules or plaques with surrounding macular erythema, and these lesions are called hives (Figure 11.15) (Figure 11.16). The hives are itchy. There is no scale. The hives may be localized or may cover the entire body. Urticaria results from mediators released from mast cells when mast cells are activated. In acute urticaria, mast cells are activated when an antigen (usually proteins) binds to IgE on the surface of mast cells. One molecule of antigen must be bound by two molecules of IgE, and when this cross-linking of two surface IgE molecules occurs, it sends the mast cell activation signal. There are two general types of mediators: 1) fast-acting mediators, produced and stored in inactivated mast cells and immediately released with activation, and 2) slow-acting mediators, only produced after a mast cell is activated. Fast-acting mediators include histamine, heparin, and proteases. Slow-acting mediators include prostaglandins, leukotrienes, and platelet-activating factor. Cytokines are also produced. The combination of mediators leads to blood vessel dilation, fluid accumulation in the tissue, WBC recruitment, and pruritus receptor activation. Treatment of acute urticaria revolves around identifying the cause of the urticaria and treating the symptoms. Symptomatic relief can be achieved with antihistamines. In severe cases, systemic steroids are necessary to effectively relieve symptoms. At “recommended” doses, the general effectiveness of antihistamines is as follows: doxepin > hydroxyzine (Atarax) > diphenhydramine (Benadryl) > cetirizine (Zyrtec) > fexofenadine (Allegra) > loratadine (Claritin). Unfortunately, the same ranking applies to the degree of sedation. Of note, antihistamines generally are extremely safe, and (except for doxepin), doses up to four times the recommended dose can be safely used in otherwise healthy patients. It is also important to remember that histamine is not the only mediator of urticaria. It is the main mediator of the itch associated with urticaria, but other mediators all contribute to the appearance of hives and its symptoms. Therefore, we should not expect antihistamines to cause complete resolution of the hives or the itch. At best, antihistamines will make hives less pruritic. Common causes of acute urticaria are environmental exposures (foods, inhaled allergens, insect exposure, medications). Less common causes are infections and autoimmune or inflammatory diseases. Chronic Urticaria (CU) CU is most common in middle-aged to menopausal females. The individual hives in CU look identical to those seen in acute urticaria. CU hives are usually more numerous and more widespread than in acute urticaria. CU is defined as hives that occur daily or almost daily for at least 6 consecutive weeks. There are several “causes” of CU. However, CU is most often idiopathic with no identifiable cause of mast cell activation/degranulation. At least 30% of cases are autoimmune in nature. These patients develop IgG antibodies directed against IgE receptor on the surface of mast cells. When the IgG antibodies bind the IgE receptor, it causes mast cell degranulation and activation. These tend to be the patients with the most severe disease. In other patients, a physical stimulus can cause mast cell degranulation and activation. The most common physical causes are pressure (hives on the back of the legs and lower back after sitting or riding in the car), increased temperature (hives after a hot shower), exercise, cold temperatures (hives in winter or hives after jumping into cold water). Treatment of CU is difficult. Antihistamines are partially effective. Using two antihistamines is best (a sedating, high-potency antihistamine in the evening and a non-sedating, lower-potency antihistamine in the morning and afternoon). In addition, an H2 blocker (ranitidine, cimetidine) can give added benefit. A leukotriene antagonist (montelukast, zafirlukast) can also be useful. For CU flares, systemic steroids are quite effective. It is important, though, to avoid chronic use of systemic steroids, as the long term side effects are severe. For patients with CU that severely impacts quality of life, three month courses of cyclosporine have shown significant benefit. After a three month cyclosporine course, 1/3 of patients will be “cured”, 1/3 will improve with a less severe residual CU, and 1/3 will have no improvement.