CME Study Center
CME #134
March 2008
Skin & Aging is proud to bring you this latest installment in its CME series. This series consists of regular CME activities that qualify you for one category 1 physician credit hour. As a reader of Skin & Aging, this course is brought to you free of charge — you aren’t required to pay a processing fee.
In this CME, Skin & Aging’s Issues in Dermatology Section Editor Gary Goldenberg, who is board certified in dermatology and dermatopathology, discusses in detail various types of pruritic dermatoses.
At the end of this article, you’ll find an exam. Mark your responses in the designated area, then fax page 62 to NACCME at (610) 560-0501.
We’ll also post this course on our Web site, which you can access at www.skinandaging.com. I hope this CME contributes to your clinical skills.
Amy McMichael, M.D.
CME Editor
Amy McMichael, M.D., is Associate Professor in the Department of Dermatology, Director of the Hair Disorders Clinic and Residency Program Director at Wake Forest University Medical Center in Winston-Salem, NC.
This CME activity is sponsored by an unrestricted grant from Sanofi-Aventis.
Principal Faculty: Gary Goldenberg, M.D.
Method of Participation: Physicians may receive 1 AMA PRA Category 1 Credit™ by reading the article on pages 55 through 61 and successfully answering the questions found on page 61. A score of 70% is required for passing. Submit your answers and evaluation via fax; or you may log on to our Web site at www.skinandaging.com.
Estimated Time to Complete Activity: 1 hour
Date of Original Release: March 1, 2008
Expiration Date: February 28, 2009
Accreditation Statement: This activity is sponsored by the North American Center for Continuing Medical Education (NACCME). NACCME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NACCME designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.™ Physicians should only claim credit commensurate with the extent of their participation in the activity. This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies.
Off-Label/Unapproved Usage Discussion: This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the FDA. Neither NACCME nor Sanofi Aventis recommends the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclosures: All those with control over the content of continuing education programs sponsored by NACCME are expected to disclose whether they do or do not have any real or apparent conflict(s) of interest or other relationships related to the content of their presentation(s). It is not assumed that these relationships will have an adverse impact on presentations; they are simply noted here to fully inform participants.
Dr. Goldenberg has disclosed that he has no significant financial relationship with any organization that could be perceived as a real or apparent conflict of interest in the context of his article.
Editor: E. Meyer has disclosed no significant financial relationship/ conflict of interest in the context of this educational activity.
Reviewer: A. McMichael, M.D., has disclosed no significant financial relationship/conflict of interest in the context of this educational activity.
Sponsor: This activity is sponsored by the North American Center for Continuing Medical Education.
Learning Objectives:
1. Identify and correlate clinical and histologic findings of pruritic dermatoses.
2. Discuss clinical presentations and differential diagnoses of pruritic dermatoses.
3. Discuss histologic findings and differential diagnoses of pruritic dermatoses.
4. Discuss treatment options for pruritic dermatoses.
Target Audience: Dermatologists
Commercial Support: This activity is supported by an educational grant from Sanofi-Aventis.
Sponsor: NACCME
Case 1 - Discussion
Treatment
This patient was treated with topical triamcinolone 0.1% cream 1:1 with silvadene 1% cream and oral antihistamines. A serologic work-up for arthropod transmitted diseases was negative and the patient improved on follow-up.
Background
Arthropod bite reaction (ABR), also known as arthropod assault, represents a dermal hypersensitivity reaction to arthropod venom and/or saliva and may be seen in tropical regions as well as in temperate climates. This complex and heterogeneous diagnostic group includes popular urticaria, as well as bites from lice, flees, bees, spiders, and ticks, among other members of phylum Arthropoda.
The pathogenesis of ABR is complex, and may be related to immediate release of histamine, serotonin, formic acid or kinins and delayed reaction to proteinaceous allergens.1 Both, cell-mediated and humoral arms of the immune system are involved.
Clinical Presentation
The clinical presentation of ABR is variable, depending on the etiology. Papular urticaria presents with pruritic small urticarial papules and plaques, which represent a hypersensitivity reaction to arthropod bites and may be secondary to bites from the cat flea (Ctenocephalides felis), the dog flea (C. canis), the human flea (Pulex irritans), and bedbug (Cimex lectularius).2,3,4 These lesions are usually distributed on the extensor surfaces of arms and legs.2
Loxosceles and Latrodectus species of spiders are another important cause of arthropod assault in United States.2 Brown recluse spider (Loxosceles reclusa) bites can present with severe ulcerative necrosis with eschar formation, a reaction know as necrotic arachnidism.5 Black widow spider (Latrodectus mactans) bites usually produce mild dermatologic manifestations, but are associated with a systemic reaction, including abdominal pain, muscle spasm, headache, nausea, vomiting, and hypertension.6,7,8,9
Management
Treatment of ABR reaction depends on the etiology of the reaction and includes local wound care, topical corticosteroids, topical and systemic antibiotics — especially if arthropod transmitted disease is suspected — and oral antihistamines. Prevention of bites is also crucial, and may be accomplished by use of repellents, including permethrin and DEET.
Case 2 - Discussion
Diagnosis
The patient was diagnosed with telangiectasia macularis eruptiva perstans and was prescribed antihistamines for as-needed use. A complete serologic work-up was negative for systemic disease.
Background
Mastocytosis represents a spectrum of clinical disorders with a common phenotype of tissue mast cell hyperplasia.10 The skin is the organ most commonly affected by mastocytosis. Cutaneous mastocytosis is a heterogeneous disorder that may be divided into four major variants: solitary and multiple mastocytomas, urticaria pigmentosa, diffuse and erythrodermic mastocytosis, and telangiectasia macularis eruptiva perstans (TMEP).11 Dysfunction of the KIT receptor, a tyrosine kinase receptor for mast cell growth factor (MCGF), and elevated levels of MCGF have been implicated in pathogenesis of mastocytosis.12 Current classification, initially proposed by Metcalfe, includes disease limited to the skin as well as systemic involvement. Systemic disease is commonly seen among older patients who display organomegaly and mast cell atypia.13
Patients with organ infiltration may display hepatomegaly, splenomegaly, lymphadenopathy, large bone osteolyses, and malabsorption with hypoalbuminemia and weight loss.13 Increased levels of histamine and its metabolite, N-methylimidazole acetic acid, have been documented in the urine and plasma of patients with systemic involvement.12
Histologically, neoplastic mast cells are present in the dermis and have a variable appearance and may display cytoplasmic distribution of fine granules and have atypical nuclei with monocytoid appearance.14,15,16 A variety of special stains, including toluidine blue, astra blue, Giemsa, chloracetate esterase, and immunohistochemistry for CD117 (C-Kit), may be used to highlight mast cells.
Use of H1 and H2 antihistamines has been reported to be an effective method of treatment.17 Nevertheless, antihistamines have also been reported to result in sudden infant death.18 Disodium cromoglycate and ketotifen have been reported to be safe medications for treatment of patients with systemic manifestations of mastocytosis. Disodium cromoglycate is specifically effective in relieving gastrointestinal and cutaneous symptoms of bullous mastocytosis (BM), while ketotifen inhibits mast cell degranulation and blocks histamine receptors.19,20 Topical high-potency corticosteroids may also reduce bulla formation.21 Narcotics, anesthetic agents, and alcohol are well-known mast cell degranulators and must be avoided by patients with BM.22 Imatinib mesylate (Glivec) is a selective Bcr-Abl protein tyrosine-kinase inhibitor and it also inhibits the receptor tyrosine-kinase for platelet derived growth factor (PDGF) and c-Kit; it has recently been reported as a treatment option for systemic mastocytosis.23
Case 3 - Discussion
Diagnosis
The patient was diagnosed with chronic urticaria. She underwent additional serologic testing to rule out collagen vascular diseases, which was negative. The patient was treated with an oral non-sedating antihistamine and improved on follow-up.
Background
Urticaria is a heterogeneous disorder group with many etiologies and variable clinical presentation. Clinically, urticaria presents with erythematous wheals, which are very pruritic and may have a pale center due to tissue edema. Deeper swellings of the dermis and subcutaneous and submucosal tissues are called angioedema.24 The clinical disease may be divided in several subgroups, including physical urticaria, contact urticaria, urticarial vasculitis, and “ordinary” urticaria.24 Chronic urticaria is defined as recurrent urticaria occurring at least twice weekly for 6 weeks.
Pathogenesis
The pathogenesis of urticaria is complex, with mast cell degranulation and histamine release central to the development of wheals and angioedema.24 Degranulation appears to be related to cross-linking of two or more adjacent Fc_RI on the mast cell membrane. This may be seen with classic type I hypersensitivity reaction, which involves binding of receptor-bound specific IgE by allergen, and immunologic degranulating stimuli that act through the IgE receptor, such as anti-IgE and anti-Fc_RI antibodies.25 Opiates, foods and food additives, as well as salycilates may be important etiologic factors as well.24,26
Histology
Histologically, urticaria presents with the typical features of urticarial tissue reaction. The epidermis is usually normal, although spongiosis may sometimes be seen. The dermis usually shows a mild perivascular and interstitial inflammatory infiltrate with lymphocytes, eosinophils and neutrophils. Superficial dermal edema is also usually present. These findings are non-specific, and may be seen with other types of urticarial tissue reaction, such as urticarial medication reaction, superficial gyrate erythema, and arthropod bite reaction, among others.
Management
Avoidance of exacerbating factors, such as salycilates, alcohol, angiotensin-converting enzyme inhibitors, and physical factors, among others, is important for management of urticaria.
Oral antihistamines are first-line treatment of chronic urticaria. Approximately 40% of patients in a large single center study reported response to H1-receptor antagonists.27 Although they may not clear urticaria completely, antihistamines may reduce pruritus, flatten wheals, shorten wheal duration, and reduce wheal number.25 Other treatment options include oral corticosteroids, sulfasalazine, colchicine, hydroxychloroquine, dapsone, and cyclosporine.24,28,29,30,31
Case 4 - Discussion
Treatment
The patient was treated with over-the-counter moisturizers, desonide 0.05% lotion BID, tacrolimus 0.1% ointment QHS, and antihistamines PRN.
Background
Atopic dermatitis (AD) is a common skin disorder with prevalence between 15% to 20%.32 The majority of AD cases arise in childhood, with approximately 60% arising before age 1.33
The etiology and pathogenesis of AD is complex. Genetic predisposition appears to be an important factor. Kang and colleagues studied 372 patients with AD and found that the incidence of personal respiratory allergy was 59%, and positive family history of atopy was 73%.34 Bohme and colleagues found that approximately 27% of children without family history of atopy develop AD, versus 38% and 50%, respectively, of children with one or two affected parents.35 Atopic dermatitis shows a biphasic cytokine profile, when comparing acute and chronic disease states; acute AD shows a type II T helper cell response (IL-4, -5, -10 predominant), while chronic AD shows a type I T helper cell response (IFNg, IL-2 predominant).36 Increased IgE production is seen in a majority of patients with AD, and may be secondary to the cytokine profile seen during the acute phase of AD.34
Histology
The histologic hallmark of AD is epidermal spongiosis. The degree of intraepidermal edema and spongiosis depends on the stage of the disease process, with pronounced spongiosis with intraepidermal vesicle formation in acute AD and mild-to-moderate spongiosis with chronic AD. A chronic perivascular dermatitis is also usually seen. The histologic differential diagnosis is quite broad, and includes spongiotic medication reaction, nummular eczema, contact dermatitis, and id reaction, among others.
There are multiple treatment options for atopic dermatitis, including preventive measures, topical corticosteroids and non-steroidal preparations, phototherapy, and systemic medications. Avoidance of possible immunologic triggers, such as foods, allergens, irritants, and infectious organisms such as Staphylococcus aureus, is very important in the management of AD.37,38 Topical corticosteroids are the first-line treatment of AD and are the standard of care to which all other treatments are compared.39 Topical calcineurin inhibitors, tacrolimus and pimecrolimus, coal tar, and doxepin may be used as steroid-sparing agents. More recently, two topical devices, Mimyx and Atopiclair, have been approved for treatment of AD. Oral options for treatment of AD include sedating and non-sedating antihistamines and immunosuppressants such as corticosteroids, mycophenolate mofetil, methotrexate, biologic agents, and intravenous immunoglobulin.39
Case 5 - Discussion
Treatment
The patient was treated with a prednisone taper, topical clobetasol 0.05% cream, and oral antihistamines. At a
2-week follow-up appointment, the patient improved. He is scheduled to undergo path testing.
Background
Contact dermatitis may be either irritant or allergic in nature. Irritant contact dermatitis accounts for approximately 80% of all contact dermatitis, while allergic contact dermatitis (ACD) accounts for approximately 20%.40 Allergic contact dermatitis is a type IV delayed hypersensitivity reaction, which is allergen-specific and requires prior sensitization of the individual to the chemical in question.41 The subsequent re-exposure, even to a low concentration of the causative chemical, leads to the presentation of the responsible allergen to an already primed T-cell milieu, leading to the release of numerous cytokines and chemotactic factors and resulting in the clinical picture of ACD.41
A recent study by Davis and colleagues examined results of patch testing performed on 3,854 patients.42 A total of 2,664 patients had at least one positive reaction (69.1%) and 1,933 patients had two or more positive reactions (50.2%). The authors concluded that metals, fragrances, topical antibiotics, preservatives, and individual allergens used in haircare products, topical corticosteroids, glues, plastics, and rubber were most often associated with positive patch-test reactions.
The clinical presentation of ACD depends on the acuteness of the process. Acute ACD usually presents with well-demarcated plaques with blisters and erythema, while chronic disease presents with more diffuse eczematous plaques.
Acute ACD presents with pronounced epidermal spongiosis and inflammatory infiltrates, which contain eosinophils. Chronic ACD usually presents with epidermal hyperplasia, which may be psoriasiform in nature, and mild epidermal spongiosis. Dermal eosinophils are usually present along with a mononuclear inflammatory infiltrate.
Limiting exposure to the responsible allergen is vital in treatment of ACD. The physician can consult the Contact Allergen Database (www.contactderm.org) for up- to-date information regarding allergens in order to educate his or her patients. Treatment options also include topical and oral corticosteroids and antihistamines.
CME Study Center
CME #134
March 2008
Skin & Aging is proud to bring you this latest installment in its CME series. This series consists of regular CME activities that qualify you for one category 1 physician credit hour. As a reader of Skin & Aging, this course is brought to you free of charge — you aren’t required to pay a processing fee.
In this CME, Skin & Aging’s Issues in Dermatology Section Editor Gary Goldenberg, who is board certified in dermatology and dermatopathology, discusses in detail various types of pruritic dermatoses.
At the end of this article, you’ll find an exam. Mark your responses in the designated area, then fax page 62 to NACCME at (610) 560-0501.
We’ll also post this course on our Web site, which you can access at www.skinandaging.com. I hope this CME contributes to your clinical skills.
Amy McMichael, M.D.
CME Editor
Amy McMichael, M.D., is Associate Professor in the Department of Dermatology, Director of the Hair Disorders Clinic and Residency Program Director at Wake Forest University Medical Center in Winston-Salem, NC.
This CME activity is sponsored by an unrestricted grant from Sanofi-Aventis.
Principal Faculty: Gary Goldenberg, M.D.
Method of Participation: Physicians may receive 1 AMA PRA Category 1 Credit™ by reading the article on pages 55 through 61 and successfully answering the questions found on page 61. A score of 70% is required for passing. Submit your answers and evaluation via fax; or you may log on to our Web site at www.skinandaging.com.
Estimated Time to Complete Activity: 1 hour
Date of Original Release: March 1, 2008
Expiration Date: February 28, 2009
Accreditation Statement: This activity is sponsored by the North American Center for Continuing Medical Education (NACCME). NACCME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NACCME designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.™ Physicians should only claim credit commensurate with the extent of their participation in the activity. This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies.
Off-Label/Unapproved Usage Discussion: This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the FDA. Neither NACCME nor Sanofi Aventis recommends the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclosures: All those with control over the content of continuing education programs sponsored by NACCME are expected to disclose whether they do or do not have any real or apparent conflict(s) of interest or other relationships related to the content of their presentation(s). It is not assumed that these relationships will have an adverse impact on presentations; they are simply noted here to fully inform participants.
Dr. Goldenberg has disclosed that he has no significant financial relationship with any organization that could be perceived as a real or apparent conflict of interest in the context of his article.
Editor: E. Meyer has disclosed no significant financial relationship/ conflict of interest in the context of this educational activity.
Reviewer: A. McMichael, M.D., has disclosed no significant financial relationship/conflict of interest in the context of this educational activity.
Sponsor: This activity is sponsored by the North American Center for Continuing Medical Education.
Learning Objectives:
1. Identify and correlate clinical and histologic findings of pruritic dermatoses.
2. Discuss clinical presentations and differential diagnoses of pruritic dermatoses.
3. Discuss histologic findings and differential diagnoses of pruritic dermatoses.
4. Discuss treatment options for pruritic dermatoses.
Target Audience: Dermatologists
Commercial Support: This activity is supported by an educational grant from Sanofi-Aventis.
Sponsor: NACCME
Case 1 - Discussion
Treatment
This patient was treated with topical triamcinolone 0.1% cream 1:1 with silvadene 1% cream and oral antihistamines. A serologic work-up for arthropod transmitted diseases was negative and the patient improved on follow-up.
Background
Arthropod bite reaction (ABR), also known as arthropod assault, represents a dermal hypersensitivity reaction to arthropod venom and/or saliva and may be seen in tropical regions as well as in temperate climates. This complex and heterogeneous diagnostic group includes popular urticaria, as well as bites from lice, flees, bees, spiders, and ticks, among other members of phylum Arthropoda.
The pathogenesis of ABR is complex, and may be related to immediate release of histamine, serotonin, formic acid or kinins and delayed reaction to proteinaceous allergens.1 Both, cell-mediated and humoral arms of the immune system are involved.
Clinical Presentation
The clinical presentation of ABR is variable, depending on the etiology. Papular urticaria presents with pruritic small urticarial papules and plaques, which represent a hypersensitivity reaction to arthropod bites and may be secondary to bites from the cat flea (Ctenocephalides felis), the dog flea (C. canis), the human flea (Pulex irritans), and bedbug (Cimex lectularius).2,3,4 These lesions are usually distributed on the extensor surfaces of arms and legs.2
Loxosceles and Latrodectus species of spiders are another important cause of arthropod assault in United States.2 Brown recluse spider (Loxosceles reclusa) bites can present with severe ulcerative necrosis with eschar formation, a reaction know as necrotic arachnidism.5 Black widow spider (Latrodectus mactans) bites usually produce mild dermatologic manifestations, but are associated with a systemic reaction, including abdominal pain, muscle spasm, headache, nausea, vomiting, and hypertension.6,7,8,9
Management
Treatment of ABR reaction depends on the etiology of the reaction and includes local wound care, topical corticosteroids, topical and systemic antibiotics — especially if arthropod transmitted disease is suspected — and oral antihistamines. Prevention of bites is also crucial, and may be accomplished by use of repellents, including permethrin and DEET.
Case 2 - Discussion
Diagnosis
The patient was diagnosed with telangiectasia macularis eruptiva perstans and was prescribed antihistamines for as-needed use. A complete serologic work-up was negative for systemic disease.
Background
Mastocytosis represents a spectrum of clinical disorders with a common phenotype of tissue mast cell hyperplasia.10 The skin is the organ most commonly affected by mastocytosis. Cutaneous mastocytosis is a heterogeneous disorder that may be divided into four major variants: solitary and multiple mastocytomas, urticaria pigmentosa, diffuse and erythrodermic mastocytosis, and telangiectasia macularis eruptiva perstans (TMEP).11 Dysfunction of the KIT receptor, a tyrosine kinase receptor for mast cell growth factor (MCGF), and elevated levels of MCGF have been implicated in pathogenesis of mastocytosis.12 Current classification, initially proposed by Metcalfe, includes disease limited to the skin as well as systemic involvement. Systemic disease is commonly seen among older patients who display organomegaly and mast cell atypia.13
Patients with organ infiltration may display hepatomegaly, splenomegaly, lymphadenopathy, large bone osteolyses, and malabsorption with hypoalbuminemia and weight loss.13 Increased levels of histamine and its metabolite, N-methylimidazole acetic acid, have been documented in the urine and plasma of patients with systemic involvement.12
Histologically, neoplastic mast cells are present in the dermis and have a variable appearance and may display cytoplasmic distribution of fine granules and have atypical nuclei with monocytoid appearance.14,15,16 A variety of special stains, including toluidine blue, astra blue, Giemsa, chloracetate esterase, and immunohistochemistry for CD117 (C-Kit), may be used to highlight mast cells.
Use of H1 and H2 antihistamines has been reported to be an effective method of treatment.17 Nevertheless, antihistamines have also been reported to result in sudden infant death.18 Disodium cromoglycate and ketotifen have been reported to be safe medications for treatment of patients with systemic manifestations of mastocytosis. Disodium cromoglycate is specifically effective in relieving gastrointestinal and cutaneous symptoms of bullous mastocytosis (BM), while ketotifen inhibits mast cell degranulation and blocks histamine receptors.19,20 Topical high-potency corticosteroids may also reduce bulla formation.21 Narcotics, anesthetic agents, and alcohol are well-known mast cell degranulators and must be avoided by patients with BM.22 Imatinib mesylate (Glivec) is a selective Bcr-Abl protein tyrosine-kinase inhibitor and it also inhibits the receptor tyrosine-kinase for platelet derived growth factor (PDGF) and c-Kit; it has recently been reported as a treatment option for systemic mastocytosis.23
Case 3 - Discussion
Diagnosis
The patient was diagnosed with chronic urticaria. She underwent additional serologic testing to rule out collagen vascular diseases, which was negative. The patient was treated with an oral non-sedating antihistamine and improved on follow-up.
Background
Urticaria is a heterogeneous disorder group with many etiologies and variable clinical presentation. Clinically, urticaria presents with erythematous wheals, which are very pruritic and may have a pale center due to tissue edema. Deeper swellings of the dermis and subcutaneous and submucosal tissues are called angioedema.24 The clinical disease may be divided in several subgroups, including physical urticaria, contact urticaria, urticarial vasculitis, and “ordinary” urticaria.24 Chronic urticaria is defined as recurrent urticaria occurring at least twice weekly for 6 weeks.
Pathogenesis
The pathogenesis of urticaria is complex, with mast cell degranulation and histamine release central to the development of wheals and angioedema.24 Degranulation appears to be related to cross-linking of two or more adjacent Fc_RI on the mast cell membrane. This may be seen with classic type I hypersensitivity reaction, which involves binding of receptor-bound specific IgE by allergen, and immunologic degranulating stimuli that act through the IgE receptor, such as anti-IgE and anti-Fc_RI antibodies.25 Opiates, foods and food additives, as well as salycilates may be important etiologic factors as well.24,26
Histology
Histologically, urticaria presents with the typical features of urticarial tissue reaction. The epidermis is usually normal, although spongiosis may sometimes be seen. The dermis usually shows a mild perivascular and interstitial inflammatory infiltrate with lymphocytes, eosinophils and neutrophils. Superficial dermal edema is also usually present. These findings are non-specific, and may be seen with other types of urticarial tissue reaction, such as urticarial medication reaction, superficial gyrate erythema, and arthropod bite reaction, among others.
Management
Avoidance of exacerbating factors, such as salycilates, alcohol, angiotensin-converting enzyme inhibitors, and physical factors, among others, is important for management of urticaria.
Oral antihistamines are first-line treatment of chronic urticaria. Approximately 40% of patients in a large single center study reported response to H1-receptor antagonists.27 Although they may not clear urticaria completely, antihistamines may reduce pruritus, flatten wheals, shorten wheal duration, and reduce wheal number.25 Other treatment options include oral corticosteroids, sulfasalazine, colchicine, hydroxychloroquine, dapsone, and cyclosporine.24,28,29,30,31
Case 4 - Discussion
Treatment
The patient was treated with over-the-counter moisturizers, desonide 0.05% lotion BID, tacrolimus 0.1% ointment QHS, and antihistamines PRN.
Background
Atopic dermatitis (AD) is a common skin disorder with prevalence between 15% to 20%.32 The majority of AD cases arise in childhood, with approximately 60% arising before age 1.33
The etiology and pathogenesis of AD is complex. Genetic predisposition appears to be an important factor. Kang and colleagues studied 372 patients with AD and found that the incidence of personal respiratory allergy was 59%, and positive family history of atopy was 73%.34 Bohme and colleagues found that approximately 27% of children without family history of atopy develop AD, versus 38% and 50%, respectively, of children with one or two affected parents.35 Atopic dermatitis shows a biphasic cytokine profile, when comparing acute and chronic disease states; acute AD shows a type II T helper cell response (IL-4, -5, -10 predominant), while chronic AD shows a type I T helper cell response (IFNg, IL-2 predominant).36 Increased IgE production is seen in a majority of patients with AD, and may be secondary to the cytokine profile seen during the acute phase of AD.34
Histology
The histologic hallmark of AD is epidermal spongiosis. The degree of intraepidermal edema and spongiosis depends on the stage of the disease process, with pronounced spongiosis with intraepidermal vesicle formation in acute AD and mild-to-moderate spongiosis with chronic AD. A chronic perivascular dermatitis is also usually seen. The histologic differential diagnosis is quite broad, and includes spongiotic medication reaction, nummular eczema, contact dermatitis, and id reaction, among others.
There are multiple treatment options for atopic dermatitis, including preventive measures, topical corticosteroids and non-steroidal preparations, phototherapy, and systemic medications. Avoidance of possible immunologic triggers, such as foods, allergens, irritants, and infectious organisms such as Staphylococcus aureus, is very important in the management of AD.37,38 Topical corticosteroids are the first-line treatment of AD and are the standard of care to which all other treatments are compared.39 Topical calcineurin inhibitors, tacrolimus and pimecrolimus, coal tar, and doxepin may be used as steroid-sparing agents. More recently, two topical devices, Mimyx and Atopiclair, have been approved for treatment of AD. Oral options for treatment of AD include sedating and non-sedating antihistamines and immunosuppressants such as corticosteroids, mycophenolate mofetil, methotrexate, biologic agents, and intravenous immunoglobulin.39
Case 5 - Discussion
Treatment
The patient was treated with a prednisone taper, topical clobetasol 0.05% cream, and oral antihistamines. At a
2-week follow-up appointment, the patient improved. He is scheduled to undergo path testing.
Background
Contact dermatitis may be either irritant or allergic in nature. Irritant contact dermatitis accounts for approximately 80% of all contact dermatitis, while allergic contact dermatitis (ACD) accounts for approximately 20%.40 Allergic contact dermatitis is a type IV delayed hypersensitivity reaction, which is allergen-specific and requires prior sensitization of the individual to the chemical in question.41 The subsequent re-exposure, even to a low concentration of the causative chemical, leads to the presentation of the responsible allergen to an already primed T-cell milieu, leading to the release of numerous cytokines and chemotactic factors and resulting in the clinical picture of ACD.41
A recent study by Davis and colleagues examined results of patch testing performed on 3,854 patients.42 A total of 2,664 patients had at least one positive reaction (69.1%) and 1,933 patients had two or more positive reactions (50.2%). The authors concluded that metals, fragrances, topical antibiotics, preservatives, and individual allergens used in haircare products, topical corticosteroids, glues, plastics, and rubber were most often associated with positive patch-test reactions.
The clinical presentation of ACD depends on the acuteness of the process. Acute ACD usually presents with well-demarcated plaques with blisters and erythema, while chronic disease presents with more diffuse eczematous plaques.
Acute ACD presents with pronounced epidermal spongiosis and inflammatory infiltrates, which contain eosinophils. Chronic ACD usually presents with epidermal hyperplasia, which may be psoriasiform in nature, and mild epidermal spongiosis. Dermal eosinophils are usually present along with a mononuclear inflammatory infiltrate.
Limiting exposure to the responsible allergen is vital in treatment of ACD. The physician can consult the Contact Allergen Database (www.contactderm.org) for up- to-date information regarding allergens in order to educate his or her patients. Treatment options also include topical and oral corticosteroids and antihistamines.
CME Study Center
CME #134
March 2008
Skin & Aging is proud to bring you this latest installment in its CME series. This series consists of regular CME activities that qualify you for one category 1 physician credit hour. As a reader of Skin & Aging, this course is brought to you free of charge — you aren’t required to pay a processing fee.
In this CME, Skin & Aging’s Issues in Dermatology Section Editor Gary Goldenberg, who is board certified in dermatology and dermatopathology, discusses in detail various types of pruritic dermatoses.
At the end of this article, you’ll find an exam. Mark your responses in the designated area, then fax page 62 to NACCME at (610) 560-0501.
We’ll also post this course on our Web site, which you can access at www.skinandaging.com. I hope this CME contributes to your clinical skills.
Amy McMichael, M.D.
CME Editor
Amy McMichael, M.D., is Associate Professor in the Department of Dermatology, Director of the Hair Disorders Clinic and Residency Program Director at Wake Forest University Medical Center in Winston-Salem, NC.
This CME activity is sponsored by an unrestricted grant from Sanofi-Aventis.
Principal Faculty: Gary Goldenberg, M.D.
Method of Participation: Physicians may receive 1 AMA PRA Category 1 Credit™ by reading the article on pages 55 through 61 and successfully answering the questions found on page 61. A score of 70% is required for passing. Submit your answers and evaluation via fax; or you may log on to our Web site at www.skinandaging.com.
Estimated Time to Complete Activity: 1 hour
Date of Original Release: March 1, 2008
Expiration Date: February 28, 2009
Accreditation Statement: This activity is sponsored by the North American Center for Continuing Medical Education (NACCME). NACCME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NACCME designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.™ Physicians should only claim credit commensurate with the extent of their participation in the activity. This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies.
Off-Label/Unapproved Usage Discussion: This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the FDA. Neither NACCME nor Sanofi Aventis recommends the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
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Learning Objectives:
1. Identify and correlate clinical and histologic findings of pruritic dermatoses.
2. Discuss clinical presentations and differential diagnoses of pruritic dermatoses.
3. Discuss histologic findings and differential diagnoses of pruritic dermatoses.
4. Discuss treatment options for pruritic dermatoses.
Target Audience: Dermatologists
Commercial Support: This activity is supported by an educational grant from Sanofi-Aventis.
Sponsor: NACCME
Case 1 - Discussion
Treatment
This patient was treated with topical triamcinolone 0.1% cream 1:1 with silvadene 1% cream and oral antihistamines. A serologic work-up for arthropod transmitted diseases was negative and the patient improved on follow-up.
Background
Arthropod bite reaction (ABR), also known as arthropod assault, represents a dermal hypersensitivity reaction to arthropod venom and/or saliva and may be seen in tropical regions as well as in temperate climates. This complex and heterogeneous diagnostic group includes popular urticaria, as well as bites from lice, flees, bees, spiders, and ticks, among other members of phylum Arthropoda.
The pathogenesis of ABR is complex, and may be related to immediate release of histamine, serotonin, formic acid or kinins and delayed reaction to proteinaceous allergens.1 Both, cell-mediated and humoral arms of the immune system are involved.
Clinical Presentation
The clinical presentation of ABR is variable, depending on the etiology. Papular urticaria presents with pruritic small urticarial papules and plaques, which represent a hypersensitivity reaction to arthropod bites and may be secondary to bites from the cat flea (Ctenocephalides felis), the dog flea (C. canis), the human flea (Pulex irritans), and bedbug (Cimex lectularius).2,3,4 These lesions are usually distributed on the extensor surfaces of arms and legs.2
Loxosceles and Latrodectus species of spiders are another important cause of arthropod assault in United States.2 Brown recluse spider (Loxosceles reclusa) bites can present with severe ulcerative necrosis with eschar formation, a reaction know as necrotic arachnidism.5 Black widow spider (Latrodectus mactans) bites usually produce mild dermatologic manifestations, but are associated with a systemic reaction, including abdominal pain, muscle spasm, headache, nausea, vomiting, and hypertension.6,7,8,9
Management
Treatment of ABR reaction depends on the etiology of the reaction and includes local wound care, topical corticosteroids, topical and systemic antibiotics — especially if arthropod transmitted disease is suspected — and oral antihistamines. Prevention of bites is also crucial, and may be accomplished by use of repellents, including permethrin and DEET.
Case 2 - Discussion
Diagnosis
The patient was diagnosed with telangiectasia macularis eruptiva perstans and was prescribed antihistamines for as-needed use. A complete serologic work-up was negative for systemic disease.
Background
Mastocytosis represents a spectrum of clinical disorders with a common phenotype of tissue mast cell hyperplasia.10 The skin is the organ most commonly affected by mastocytosis. Cutaneous mastocytosis is a heterogeneous disorder that may be divided into four major variants: solitary and multiple mastocytomas, urticaria pigmentosa, diffuse and erythrodermic mastocytosis, and telangiectasia macularis eruptiva perstans (TMEP).11 Dysfunction of the KIT receptor, a tyrosine kinase receptor for mast cell growth factor (MCGF), and elevated levels of MCGF have been implicated in pathogenesis of mastocytosis.12 Current classification, initially proposed by Metcalfe, includes disease limited to the skin as well as systemic involvement. Systemic disease is commonly seen among older patients who display organomegaly and mast cell atypia.13
Patients with organ infiltration may display hepatomegaly, splenomegaly, lymphadenopathy, large bone osteolyses, and malabsorption with hypoalbuminemia and weight loss.13 Increased levels of histamine and its metabolite, N-methylimidazole acetic acid, have been documented in the urine and plasma of patients with systemic involvement.12
Histologically, neoplastic mast cells are present in the dermis and have a variable appearance and may display cytoplasmic distribution of fine granules and have atypical nuclei with monocytoid appearance.14,15,16 A variety of special stains, including toluidine blue, astra blue, Giemsa, chloracetate esterase, and immunohistochemistry for CD117 (C-Kit), may be used to highlight mast cells.
Use of H1 and H2 antihistamines has been reported to be an effective method of treatment.17 Nevertheless, antihistamines have also been reported to result in sudden infant death.18 Disodium cromoglycate and ketotifen have been reported to be safe medications for treatment of patients with systemic manifestations of mastocytosis. Disodium cromoglycate is specifically effective in relieving gastrointestinal and cutaneous symptoms of bullous mastocytosis (BM), while ketotifen inhibits mast cell degranulation and blocks histamine receptors.19,20 Topical high-potency corticosteroids may also reduce bulla formation.21 Narcotics, anesthetic agents, and alcohol are well-known mast cell degranulators and must be avoided by patients with BM.22 Imatinib mesylate (Glivec) is a selective Bcr-Abl protein tyrosine-kinase inhibitor and it also inhibits the receptor tyrosine-kinase for platelet derived growth factor (PDGF) and c-Kit; it has recently been reported as a treatment option for systemic mastocytosis.23
Case 3 - Discussion
Diagnosis
The patient was diagnosed with chronic urticaria. She underwent additional serologic testing to rule out collagen vascular diseases, which was negative. The patient was treated with an oral non-sedating antihistamine and improved on follow-up.
Background
Urticaria is a heterogeneous disorder group with many etiologies and variable clinical presentation. Clinically, urticaria presents with erythematous wheals, which are very pruritic and may have a pale center due to tissue edema. Deeper swellings of the dermis and subcutaneous and submucosal tissues are called angioedema.24 The clinical disease may be divided in several subgroups, including physical urticaria, contact urticaria, urticarial vasculitis, and “ordinary” urticaria.24 Chronic urticaria is defined as recurrent urticaria occurring at least twice weekly for 6 weeks.
Pathogenesis
The pathogenesis of urticaria is complex, with mast cell degranulation and histamine release central to the development of wheals and angioedema.24 Degranulation appears to be related to cross-linking of two or more adjacent Fc_RI on the mast cell membrane. This may be seen with classic type I hypersensitivity reaction, which involves binding of receptor-bound specific IgE by allergen, and immunologic degranulating stimuli that act through the IgE receptor, such as anti-IgE and anti-Fc_RI antibodies.25 Opiates, foods and food additives, as well as salycilates may be important etiologic factors as well.24,26
Histology
Histologically, urticaria presents with the typical features of urticarial tissue reaction. The epidermis is usually normal, although spongiosis may sometimes be seen. The dermis usually shows a mild perivascular and interstitial inflammatory infiltrate with lymphocytes, eosinophils and neutrophils. Superficial dermal edema is also usually present. These findings are non-specific, and may be seen with other types of urticarial tissue reaction, such as urticarial medication reaction, superficial gyrate erythema, and arthropod bite reaction, among others.
Management
Avoidance of exacerbating factors, such as salycilates, alcohol, angiotensin-converting enzyme inhibitors, and physical factors, among others, is important for management of urticaria.
Oral antihistamines are first-line treatment of chronic urticaria. Approximately 40% of patients in a large single center study reported response to H1-receptor antagonists.27 Although they may not clear urticaria completely, antihistamines may reduce pruritus, flatten wheals, shorten wheal duration, and reduce wheal number.25 Other treatment options include oral corticosteroids, sulfasalazine, colchicine, hydroxychloroquine, dapsone, and cyclosporine.24,28,29,30,31
Case 4 - Discussion
Treatment
The patient was treated with over-the-counter moisturizers, desonide 0.05% lotion BID, tacrolimus 0.1% ointment QHS, and antihistamines PRN.
Background
Atopic dermatitis (AD) is a common skin disorder with prevalence between 15% to 20%.32 The majority of AD cases arise in childhood, with approximately 60% arising before age 1.33
The etiology and pathogenesis of AD is complex. Genetic predisposition appears to be an important factor. Kang and colleagues studied 372 patients with AD and found that the incidence of personal respiratory allergy was 59%, and positive family history of atopy was 73%.34 Bohme and colleagues found that approximately 27% of children without family history of atopy develop AD, versus 38% and 50%, respectively, of children with one or two affected parents.35 Atopic dermatitis shows a biphasic cytokine profile, when comparing acute and chronic disease states; acute AD shows a type II T helper cell response (IL-4, -5, -10 predominant), while chronic AD shows a type I T helper cell response (IFNg, IL-2 predominant).36 Increased IgE production is seen in a majority of patients with AD, and may be secondary to the cytokine profile seen during the acute phase of AD.34
Histology
The histologic hallmark of AD is epidermal spongiosis. The degree of intraepidermal edema and spongiosis depends on the stage of the disease process, with pronounced spongiosis with intraepidermal vesicle formation in acute AD and mild-to-moderate spongiosis with chronic AD. A chronic perivascular dermatitis is also usually seen. The histologic differential diagnosis is quite broad, and includes spongiotic medication reaction, nummular eczema, contact dermatitis, and id reaction, among others.
There are multiple treatment options for atopic dermatitis, including preventive measures, topical corticosteroids and non-steroidal preparations, phototherapy, and systemic medications. Avoidance of possible immunologic triggers, such as foods, allergens, irritants, and infectious organisms such as Staphylococcus aureus, is very important in the management of AD.37,38 Topical corticosteroids are the first-line treatment of AD and are the standard of care to which all other treatments are compared.39 Topical calcineurin inhibitors, tacrolimus and pimecrolimus, coal tar, and doxepin may be used as steroid-sparing agents. More recently, two topical devices, Mimyx and Atopiclair, have been approved for treatment of AD. Oral options for treatment of AD include sedating and non-sedating antihistamines and immunosuppressants such as corticosteroids, mycophenolate mofetil, methotrexate, biologic agents, and intravenous immunoglobulin.39
Case 5 - Discussion
Treatment
The patient was treated with a prednisone taper, topical clobetasol 0.05% cream, and oral antihistamines. At a
2-week follow-up appointment, the patient improved. He is scheduled to undergo path testing.
Background
Contact dermatitis may be either irritant or allergic in nature. Irritant contact dermatitis accounts for approximately 80% of all contact dermatitis, while allergic contact dermatitis (ACD) accounts for approximately 20%.40 Allergic contact dermatitis is a type IV delayed hypersensitivity reaction, which is allergen-specific and requires prior sensitization of the individual to the chemical in question.41 The subsequent re-exposure, even to a low concentration of the causative chemical, leads to the presentation of the responsible allergen to an already primed T-cell milieu, leading to the release of numerous cytokines and chemotactic factors and resulting in the clinical picture of ACD.41
A recent study by Davis and colleagues examined results of patch testing performed on 3,854 patients.42 A total of 2,664 patients had at least one positive reaction (69.1%) and 1,933 patients had two or more positive reactions (50.2%). The authors concluded that metals, fragrances, topical antibiotics, preservatives, and individual allergens used in haircare products, topical corticosteroids, glues, plastics, and rubber were most often associated with positive patch-test reactions.
The clinical presentation of ACD depends on the acuteness of the process. Acute ACD usually presents with well-demarcated plaques with blisters and erythema, while chronic disease presents with more diffuse eczematous plaques.
Acute ACD presents with pronounced epidermal spongiosis and inflammatory infiltrates, which contain eosinophils. Chronic ACD usually presents with epidermal hyperplasia, which may be psoriasiform in nature, and mild epidermal spongiosis. Dermal eosinophils are usually present along with a mononuclear inflammatory infiltrate.
Limiting exposure to the responsible allergen is vital in treatment of ACD. The physician can consult the Contact Allergen Database (www.contactderm.org) for up- to-date information regarding allergens in order to educate his or her patients. Treatment options also include topical and oral corticosteroids and antihistamines.
