CHAPTER 7
ERYTHEMATOUS LESIONS OF THE SKIN
（紅斑性疾患）
I. Introduction
Erythema is redness of the skin caused by an increased blood flow within the superficial dilated blood vessels. Erythematous lesions will blanche when pressure is applied, but can be commonly characteristic of many skin diseases including vasculitis. Some of these erythematous lesions later become more purpuric and eventually may cause ulceration. Some ulcers, however, may occur without having any erythematous signs before the onset.
|
CLASSIFICATION OF MAJOR ERYTHEMATOUS SKIN LESIONS |
|
|
TYPE |
ENTITIES |
|
I. NON-PURPURIC ERYTHEMA A. Transient - palpable
-- non-palpable/ |
Urticaria（蕁麻疹）, angioedema（血管浮腫） Blushing, flushing |
|
B. Persistent 1. Erythema multiforme (EM)（多形紅斑）
2. Diffuse |
EM minor, EM major |
|
Toxic epidermal necrolysis/Epidermal necrolytic（表皮壊死） Staphylococcal scalded skin syndrome |
|
|
|
Papular urticaria/Papular（丘疹性） |
|
|
Erythema nodosum/Nodular（結節性） |
|
|
Erythema annulare centrifugum/Figurate |
|
Toxic shock syndrome/Acral（末端性） |
|
|
|
Livedo reticularis/Reticulated（網状） |
|
II. PURPURIC A. Non-inflammatory (non-palpable purpura) |
Senile purpura, thrombocytopenic purpura, purpura fulminans |
|
B. Inflammatory = Vasculitis (palpable purpura) 1. Infectious 2. Non-Infectious Large Vessel Medium Vessel Small Vessel |
Gonococcemia/SBE
Temporal arteritis Polyarteritis nodosum Hypersensitivity vasculitis (leucocytoclastic vasculitis), Henoch-Schonlein purpura |
Erythema can be non-purpuric or purpuric. Non-purpuric erythema blanches with pressure, when applied with microscope slide (diascopy) examination, implying no extravasation of red blood cells. If RBC's are extravasated during the course of vasculitis, the red color contributes to the perivascular tissue and would not blanche with pressure.
II. Non-Purpuric Skin Diseases
A. Urticaria（蕁麻疹）/Angioedema（血管浮腫）
1. Definition
a. A vascular reaction of the skin in which a smooth, evanescent, edematous lesion (wheals) form that may be more red, or paler, than the surrounding skin.
b. may result from many different causes; but heat, drugs, infections, and emotional stress are the most frequent causes.
c. a common problem, affecting more than 20% of the population at some time in their lives.
2. Classification
Three major groups including immunologic urticaria, non-immunologic urticaria and idiopathic urticaria.
3. Pathophysiology
a. Type I immunoreaction mediated by IgE: the most common immunologic mechanism, causing histamine release into the skin. This reaction causes vascular dilatation and increased vascular permeability that results in the formation of localized dermal edema.
b. Mast cells: an important factor in the production of most cases of urticaria. The degranulation of the mast cell leads to the release of histamine, which is a key mediator of urticaria.
4. Angioedema（血管浮腫）
a. When edematous processes extend into the dermis and/or subcutaneous and some mucosal layers, it is known as angioedema.
b. In contrast, if the edema involves the superficial portion of the dermis, it is called urticaria.
c. Angioedema commonly affects the face or a portion of the extremities.
d. May be life threatening
e. Recurrent episode of hereditary angioedema occurs in association with a genetic deficiency of the inhibition of the activated first complement component as a result of a quantitative or functional deficiency of C1-inhibitor (C1-INH).
5. Chronic Urticaria（慢性蕁麻疹）
a. An urticarial eruption that persists for more than 2 months.
b. In 80-90% of cases, the exact case is never established.
c. Multiple allergens sometimes may have caused the reaction.
d. Underlying diseases such as collagen vascular disease, cancer, parasitic and parasitic infections must be considered.
|
ETIOLOGIC CLASSIFICATION OF URTICARIA/ANGIOEDEMA |
|
I. IMMUNOLOGIC URTICARIA（免疫性蕁麻疹） A. IgE-dependent 1. Atopic diathesis（アトピー性素因） 2. Specific antigen sensitivity (e.g., foods, drugs) 3. Physical a) Dermographism c) Light b) Cold d) Cholinergic
B. Complement-mediated 1. Hereditary angioedema（遺伝性血管浮腫） 2. Acquired angioedema with lymphoma 3. Necrotizing vasculitis（壊死性血管炎） 4. Serum sickness（血清病） 5. Reactions to blood products
II. NON-IMMUNOLOGIC URTICARIA（非免疫性蕁麻疹） A. Direct mast cell-releasing agents 1. Opiates（アヘン剤） 3. Curare, d-tubocurarine 2. Antibiotics 4. Radiocontrast media
B. Agents which presumably alter Arachidonic acid metabolism 1. Aspirin and nonsteroidal anti-inflammatory agents 2. Azo dyes and benzoates
III. IDIOPATHIC URTICARIA（本態性蕁麻疹） |
6. Treatment
Removal of inciting factors
a. antihistamines H1 and H2 blockers
b. tricyclic antidepressants
c. corticosteroids (systemic or topical)
B. Erythema Multiforme（多形紅斑）
1. Definition
a. Acute, usually self-limited reaction pattern in the skin and mucous membranes characterized by multiforme lesions including macules, papules, vesicles, and bullae.
b. The whole mark of the eruption is the iris, or target lesion
2. Pathophysiology
An immune-mediated disorder with many possible etiological factors
|
SUSPECTED ETIOLOGIC FACTORS IN ERYTHEMA MULTIFORME |
|
|
INFECTIONS |
|
|
Viral Infections |
Coxsackie (B5), Herpes Simplex Infectious mononucleosis |
|
Mycoplasma infections |
M. pneumoniae |
|
Bacterial infections |
Hemolytic streptococci, Leprosy, Pseudomonas, Staphylococcus |
|
Parasite infections |
Trichomoniasis |
|
Fungous infections |
Dermatophytosis, Histoplasmosis |
|
PHYSICAL FACTORS |
Cold, Sunlight, X-ray therapy |
|
ENDOCRINE FACTORS |
Menstruation, Pregnancy |
|
DRUGS |
Antibiotics, especially penicillin Anticonvulsants, especially hydantoins Antipyretics, Analgesics Barbiturates, Sulphonamides, Tetracycline |
|
NEOPLASIA |
Internal carcinoma, Leukemia, Lymphoma, Multiple myeloma |
|
COLLAGEN DISEASES AND VASCULITIS |
Dermatomyositis, Lupus erythematosus, Polyarteritis nodosa, Rheumatoid arthritis |
|
CONTACT REACTIONS |
Poison oak |
|
MISCELLANEOUS CONDITIONS |
Dental extractions Foods |
3. Clinical Variants
a. Stevens-Johnson Syndrome - Erythema multiforme major
1) Involvement of mucous membranes and severe blistering
2) Often severe life-threatening attack lasting 4-6 weeks and accompanied by high fever
b. Toxic Epidermal Necrolysis（中毒性表皮壊死剥離症）
1) A rare life-threatening variant of erythema multiforme
2) Eruption may begin as blotchy erythema but rapidly progresses to bullae, with sloughing of large areas of full- thickness epidermis
3) Produces a scalded appearance and leaves the patient devoid of the skin's barrier function
4) Usually occurs in adults, secondarily to drugs and is lethal in about 30% of cases
|
ETIOLOGIC FACTORS IMPLICATED IN TOXIC EPIDERMAL NECROLYSIS |
|
|
Drug |
Sulfonamides, Barbiturates, Hydantions, Antibiotics, Sulfones |
|
Viral Infection |
Herpes simplex, Zoster |
|
Bacterial Infection |
E. coli septicemia |
|
Fungal Infection |
Pulmonary aspergillosis |
|
Vaccination |
Smallpox, Pulmonary aspergillosis, Smallpox, Measles, Poliomyelitis |
|
Neoplastic Disease |
Lymphomas, Leukemias |
|
Graft-vs.-host Reaction |
|
4. Treatment
a. Treatment of Mild (minor) Erythema Multiforme
Resolves spontaneously and may not require any systemic treatment.
b. Treatment of Severe (major) Erythema Multiforme (Stevens-Johnson Syndrome)
1) Oral Corticosteroids (Prednisone 20-60 mg/QD)
2) Analgesics
3) Topical Care
c. Treatment of Toxic Epidermal Necrolysis
It is always a life-threatening emergency requiring hospitalization. The most severe cases are ideally treated in Burn Units:
1) Local compresses with a solution of dilute silver nitrate (0.25%) or dilute acetic acid solution (0.1%)
2) Careful debridement of necrotic tissue and application of silver sulfadiazine
3) Oral corticosteroids (Prednisone 60 mg/QD with slow tapering of dosage over 6-8 weeks)
4) Antibiotic therapy; the most common cause of death is infection and immediate cultures (blood, sputum) should be obtained at the first sign of infection and appropriate antibiotic therapy instituted.
C. Staphylococcal Scalded Skin Syndrome (Ritter's Disease)（ぶどう球菌性熱傷様皮膚症候群）
1. Definition
a. Uncommon disease occurring predominantly in neonates and young children but occasionally in immunosuppressed adults.
b. Produces scalded skin appearance with diffuse erythema and exfoliation of large sheets of superficial epidermis.
2. Pathophysiology
a. Like bullous impetigo, staphylococcal scalded skin syndrome is caused by a phage group 2 staphylococcus.
b. The focal infection, such as the pharynx or conjunctiva, leads to the production of staphylococcal toxin called exfoliatin which binds to the epidermal granular zone and causes a superficial intraepidermal split to occur.
3. Clinical Characteristics and Diagnosis
a. The skin peels off in sheets, leaving large denuded areas. Before peeling begins, the skin is red and tender to palpation. Nikolsky's sign positive.
b. Usually resolves spontaneously over a 2-3 week period.
4. Treatment
a. Standard therapy: a course of semisynthetic penicillin derivatives (e.g., dicloxacillin) or cephalosporins for at least 2 week periods or Erythromycin if the patient is allergic to penicillin.
b. Prognosis in children is excellent even without therapy.
D. Erythema Nodosum（結節性紅斑）
1. Definition
a. A form of inflammation of subcutaneous fat (panniculitis), causing tender erythematous nodules usually located on the anterior tibial areas.
b. Thought to be caused by a hypersensitivity reaction to drugs, disease processes, or infections.
|
ETIOLOGIC ASSOCIATIONS FOR ERYTHEMA NODOSUM |
|
|
Infectious Agents |
Tuberculosis (children), coccidioidomycosis Histoplasmosis, 8-hemolytic streptococcus, Yersinia organisms, lymphogranuloma venereum |
|
Drugs |
Sulfonamides, oral contraceptives |
|
Miscellaneous |
Sarcoidosis (quite often), ulcerative colitis, Behcet's syndrome, idiopathic " 40%, lymphoma |
2. Clinical Characteristics and Causes
a. Acute self-limited eruption, characterized by painful erythematous nodules on the pretibial area that heat without ulceration.
b. Resolves spontaneously in 2 weeks but chronic recurrent or generalized forms may occur, suggesting a serious underlying disease such as lymphoma, ulcerative colitis or sarcoidosis.
III. Purpuric Erythema（紫斑性紅斑）- Non-Palpable（非触診性）
Non-palpable purpura signifies leakage of blood from the dermal blood vessels into the surrounding tissue. Because there is little or no inflammation, the lesions are nonpalpable.
A. Senile Purpura（老人性紫斑）
1. Definition and Pathophysiology
a. Violaceous macular areas develop at sites of minor trauma, more commonly in the elderly
b. Due to progressive degeneration of supporting perivascular connective tissue and consequent weakness of vessel walls caused by the aging processes and chronic exposure to the sun
2. Clinical Characteristics
a. Round or oval ecchymotic lesions, 0.5-5 cm in diameter, associated with easy bruising
b. Lesions will regress slowly over several weeks, usually asymptomatic
B. Purpura Fulminans（電撃性紫斑）
1. Definition
a. One of the clinical syndromes produced by disseminated intravascular coagulation (DIC)
b. Acute and often fatal hemorrhagic infarctive process affecting the skin and certain internal organs
2. Pathophysiology
a. DIC with endothelial injury from activity of the causative organisms and platelet damage and aggregation of initiating events
b. Hemorrhage rather than microthrombosis is the major clinical problem
3. Clinical Characteristics and Cause
a. A tender, rapidly enlarging ecchymoses with sharp irregular borders, bullae, surrounding erythema, and a tendency toward central necrosis forming large areas of ulceration eventually.
b. Death frequently occurs within 48-72 hours.
4. Treatment
a. Medical emergency requiring coordinated hematologic, pediatric, dermatologic, and surgical management.
b. Treatment of underlying infection is the most important general aspect of therapy and should be instituted as soon as possible following supportive measures (treatment of shock, anemia, and renal failure).
IV. Inflammatory Purpura（炎症性紫斑）(Vasculitis Palpable Purpura, Necrotizing Vasculitis)
Correlative clinical and pathologic observations have made it clear that palpable purpuric skin lesions can be equated with necrotizing vasculitis, i.e., inflammatory destruction of blood vessel walls. (⇒See Chapter 11 )
1. Infection
Gonococcemia / SBE
2. Non-Infectious
a. Large Bessel − Temporal arteritis
b. Medium Vessel − Polyarteritis nodosum
c. Small Vessel − Hypersensitivity vasculitis (leucocytoclastic vasculitis),
Henoch-schonlein purpura