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Sections Cutaneous Manifestations of Hepatitis C
Overview
Presentation
DDx
Treatment
Guidelines
Questions & Answers
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References

Overview

Practice Essentials

Cutaneous symptoms or findings relevant to hepatitis C virus (HCV) infection manifest in 20-40% of patients presenting to dermatologists and in a significant percentage (15-20%) of general patients. HCV is suggested and must appear in the differential diagnosis of these patients to avoid missing this important but occult factor in clinical disease in the appropriate setting.

Extrahepatic manifestations of HCV are numerous.^[1] The most prevalent and most closely linked with HCV is essential mixed cryoglobulins with dermatologic, neurologic, renal, and rheumatologic complications. It is evident in up to half of patients with chronic hepatitis C infection.^{[2, 3]} A less definite relationship to HCV is observed with systemic vasculitis, porphyria cutanea tarda, and the sicca syndromes.^{[4, 5, 6, 7]}

HCV is a major public health problem because it causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HCV also induces extrahepatic manifestations such as mixed cryoglobulinemia, porphyria cutanea tarda, leukocytoclastic vasculitis, lichen planus (LP), and sicca syndrome, all of which should be regarded as early markers of a potentially fatal chronic liver disease.^[8] Other commonly encountered dermatological disorders linked with HCV infection globally include urticaria, pruritus, thrombocytopenic purpura, and psoriasis.^{[9, 10, 11]} HCV has been postulated to up-regulate inflammatory cytokines that enhance susceptibility to psoriasis.^[12] Chronic HCV reactivation in a psoriatic patient treated with guselkumab was reported.^[13]Unfortunately, testing for this viral infection, even among those Americans commercially insured who inject drugs, especially male rural residents with skin infections, is infrequent.^[14]

Signs and symptoms

See Presentation.

Diagnostics

In August 2012, the Centers for Disease Control and Prevention (CDC) expanded their existing, risk-based testing guidelines to recommend a 1-time blood test for hepatitis C virus (HCV) infection in baby boomers—the generation born between 1945 and 1965, who account for approximately three fourths of all chronic HCV infections in the United States—without prior ascertainment of HCV risk (see Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965).^[15] One-time HCV testing in this population could identify nearly 808,600 additional people with chronic infection. All individuals identified with HCV should be screened and/or managed for alcohol abuse, followed by referral to preventative and/or treatment services, as appropriate.

Circulating autoantibodies linked with underlying autoimmune disease in those with HCV include rheumatoid factor, antinuclear antibody, anti-SSA/anti-SSB antibody, cryoglobulin, antineutrophil cytoplasmic antibody, antismooth muscle antibody, and antiliver autoantibody, and antithyroid autoantibody.^[16]

Histologic and other findings should be sought in standard references concerning each disorder.

Management

Also see Guidelines and Prevention.

Treatment of patients with extrahepatic dermatologic manifestations of hepatitis C virus (HCV) infection is the same as that of HCV infective state and the customary treatments of the individual conditions. Many, if not all, of the dermatologic manifestations disappear when appropriate HCV treatment or viral clearance occurs. HCV is the main cause of mixed cryoglobulinemia vasculitis, which should be treated, with new options including a combination of potent direct-acting antiviral agents and biological medications, especially rituximab.^{[17, 18]} HCV-related cryoglobulinemic vasculitis and polyarteritis nodosa may merit antiviral therapy and corticosteroids.^[19] Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations. Malignant conditions may even disappear with effective therapy for the underlying chronic hepatitis C infection.

Currently, medical treatment of patients with HCV infection consists of interferon and ribavirin therapy. Medical therapy for patients with individual extrahepatic dermatologic manifestations of HCV infection depends on the condition.

Cryoglobulinemic vasculitis may produce nonhealing cutaneous ulcers, sometimes impetiginized and gangreneous. A combined approach with systemic and local therapy plus sharp ulcer debridement and suitable dressing and pain management may provide pivotal care.^[20]

Consultations

Involving specialists for both treatment and follow-up care often maximizes the care of individuals with extrahepatic cutaneous manifestations of hepatitis C virus (HCV). Monitoring of liver status and liver disease progression is beyond the usual purview of dermatologists and may necessitate consultation with gastroenterologists and hepatic specialists in the care of patients.

Cutaneous manifestations, serious vasculitis, lymphomas, hepatomas, and metabolic disorders may require high-level management with a team approach. Individual specialists may be an important resource in the care of patients.

Complications

HCV may be treated with pegylated interferon-alpha/ribavirin, with dermatological adverse events uncommonly producing premature therapy discontinuation.^[21]

Long-term monitoring

Treatment of various primary, secondary, tertiary, hepatitis C virus (HCV)–related, and associated conditions is for the individual conditions. The continued successful care of patients requires attention to the underlying HCV infection of the hepatocytes and the extracutaneous disorder of symptoms.

Background

The hepatitis C virus (HCV) is an RNA virus. HCV is a major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Persons who inject illegal drugs, people who snort cocaine with shared straws, and health care workers who are at risk for needlestick and other exposures are at highest risk for HCV infection. Another major risk factor for HCV is high-risk sexual behavior. The incidence of acute HCV infection has sharply decreased in the United States during the past decade, but its prevalence remains high (approximately 2.7 million Americans) because chronic hepatitis C (CHC) infection develops in approximately 75% of patients acutely infected.

Most patients with acute and chronic infection are asymptomatic. Patients and health care providers may detect no indications of the conditions for long periods; however, chronic hepatitis C infection and chronic active hepatitis are slowly progressive diseases and result in severe morbidity in 20-30% of infected persons. Astute observation and integration of findings of extrahepatic symptoms, signs, and disease are often the first clues to underlying HCV infection.

Pathophysiology

Chronic hepatitis C infection is associated with many extrahepatic manifestations in joints, muscles, neural and gastrointestinal tissues, and skin. In this article, the many dermatologic manifestations of hepatitis C virus (HCV) are classified according to diseases with proven or suspected etiology or causation.

Primary causation results from direct infection of HCV in the skin, lymphocytes, dendric antigen-presenting cells, and blood vessels. An example of this type of disorder is the recent finding of epidermal cells with HCV-RNA particles.

Secondary causation occurs when HCV infection manifests in the skin due to epiphenomena resulting from the disruption of immune responses. Leukocytoclastic vasculitis due to cryoglobulinemia is a good example of a specific skin manifestation resulting from the production of immunoglobulins, with rheumatoid characteristics causing an immune complex–mediated vasculitis.

Tertiary causation of dermatologic manifestations results when the disruption of another organ infected or affected by HCV causes skin manifestations that are nonspecific and typical of skin responses to that organ; these responses result from a wide range of causes, including flushing and other findings of thyroid hormone release in early HCV-linked autoimmune thyroiditis. Chronic active hepatitis leading to fibrotic liver disease in chronic hepatitis C infection can also cause cutaneous vascular changes, such as spider nevus and palmar erythema. Arteriovenous hemangioma, a benign acquired cutaneous vascular lesion, has also been reported to be associated with chronic liver disease, including chronic active hepatitis associated with HCV infection.

Another category of dermatologic manifestations in HCV infections in a causative schema includes those diseases in which an association has been identified, but the details of causation have not yet been clarified. Porphyria cutanea tarda (PCT) is a good example of this type of HCV-related disease in which causation is unexplained but undeniable. In patients with PCT, 70% are HCV positive.^{[6, 7]}

Neoplastic dermatologic manifestations are another category of extrahepatic findings.

Dermatologic manifestations are associated with treatments of HCV infection, especially interferon.

The last category is suspected associations of the disorder in a causative schema. HCV genomic analysis by means of arduous gene sequencing of many viruses has led to the division of HCV into genotypes based on homology. Arabic numerals denote the genotype, and a letter denotes the subtype for lesser homology within each genotype.^[22]Note the following:

Genotype 1a occurs in 50-60% of patients in the United States. This type is difficult to eradicate using current medications.
Genotype 1b occurs in 15-20% of patients in the United States. Subtype 1b is difficult to eradicate using current medications. This type is most prevalent in Europe, Turkey, and Japan.
Genotype 1c occurs in less than 1% of patients in the United States.
Genotypes 2a, 2b, and 2c occur in 10-15% of patients in the United States. These subtypes are widely distributed and are most responsive to medication.
Genotypes 3a and 3b occur in 4-6% of patients in the United States. These subtypes are most prevalent in India, Pakistan, Australia, and Scotland.
Genotype 4 occurs in less than 5% of patients in the United States. It is most prevalent in the Middle East and Africa.
Genotype 5 occurs in less than 5% of patients in the United States. It is most prevalent in South Africa.
Genotype 6 occurs in less than 5% of patients in the United States. It is most prevalent in Hong Kong and Macao.

Etiology

The causes of extrahepatic dermatologic manifestations of hepatitis C virus (HCV) infection relate to the nature of the virus, the method of infection, host responses to HCV infection, and myriad feedback considerations. HCV is a flavivirus with a positive sense single-strand RNA (ssRNA); the ends of the RNA are conserved. HCV RNA encodes 3300 amino acids. The polyprotein encoded is cleaved by host and viral proteases to yield at least 9 polypeptide proteins, core peptides, and viral envelope proteins E1 and E2 (which encode for glycoprotein spikes set in the host cell membrane derived envelope).

Six nonstructural (NS) proteins, termed NS2, NS3, NS4a, NS4b, NS5a, and NS5b, include RNA polymerase, cyclase, and other proteins necessary for viral replication. Hypervariable regions of the E2 envelope protein are responsible for quasi-species generation. Some nonessential sequences of NS genes also create variability in antigenic structure. Mutation of NS3 sections results in escape mutants that conserve essential viral functions while interfering with host T-cell function by down-regulating interleukin 2 and interferon gamma function and up-regulating interleukin 10.^[23]

The chronicity of infection also relates to inoculum size, with high rates and worse disease in patients who have undergone transfusions and organ transplantation. The resulting persistent infection and immune stimulation create the many immunologic epiphenomenon, such as LP, mixed cryoglobulinemia, and thyroiditis. A generation of factors unfavorable to apoptosis control functions may favor malignant transformation in chronic hepatitis C infection.

Primary dermatologic disorders of chronic hepatitis C infection

Lichen planus

HCV particles are found in immune lymphocytes, macrophages, and dendritic cells, as well as in epithelial cells and cells of blood vessels.^{[24, 25, 26]}

In LP, HCV replicates in OLP epithelial cells of lesional and nonlesional skin cells. What role this plays in developing the LP host response is not known. HCV perturbs the class II host response by impairing the ability of the dendritic or antigen-presenting cell to stimulate a good T-cell response.^[27]

Lower expression of interferon gamma and interleukin 12 causes a blunted T-cell response to allostimulatory non–self-related new antigen. Another mechanism of class II immune response inhibition results from the hypervariable region (HVR-1) of envelope protein E2 suppressing CD4⁺ lymphocytes, which are stimulated to respond to HCV. The HVR-1 acts as a T-cell receptor antagonist.^[28]

A theory of causation, termed the superantigen theory of immune stimulation (which includes LP and many other immune-related disorders in which exact causation is a mystery), suggests that the human leukocyte antigen (HLA) class II response was disturbed. Superantigens, such as bacterial proteins and toxins, were proposed to act outside the HLA binding site to broadly stimulate an immune nonspecific response of wide varieties of T cells, including antiself immune responses.

Some leukocytoclastic reactions

Type II cryoglobulinemias in which IgM is the macromolecular rheumatoid antibody are more common than type III cryoglobulinemias. IgG was directed toward NS proteins and structural proteins. IgM antigen was the core protein, suggesting cross-reactivity to IgG.^[29]Co-affinity of IgM anticore antibody to IgG may be a mechanism in the formation of the cryoprecipitate.

Sialadenitis

This condition is a capillaritis of the accessory and main salivary glands and the eyes.

Secondary dermatologic disorders of chronic hepatitis C infection (mostly as a result of perturbations of the immune system

Cryoglobulinemia

Leukocytoclastic vasculitis of the skin, kidneys, joints, and eyes is present. Immune stimulation of T-cell clones in HCV infection produces monoclonal macroglobulins with co-affinity to a constituent of HCV and IgG. Stimulation of this rheumatoid factor is driven by anti-HCV activity sustained by the ongoing mutation of the virus. The same pathogenesis is involved for NHL associated with HCV.^[3]

The mean cryoprecipitate result was 2% in one study^[29]but can be greater. Immunoglobulin M (IgM) directed to a core protein sequence of HCV was also directed to a homologous immunoglobulin G (IgG) heavy-chain amino acid sequence. IgG was directed to structural and nonstructural components of HCV. The material is usually monomeric IgM molecules with high affinity for IgG (also termed rheumatoid IgM molecules or rheumatoid factor).

Type I cryoglobulinemias are caused by macroglobulins, such as in Waldenström macroglobulinemia, or IgG in which sludging results from massive molecules congealing in cooled venules of the lower leg.

Type II mixed cryoglobulins have a monoclonal rheumatoid species but vary in the IgG antigen, which is nonspecific.

Type III mixed cryoglobulinemias result from specific reactions of immunoglobulins to a single or well-defined antigen or various antigens, but the antibody species and the antigen are not monoclonal.

HCV-related systemic vasculitis may also occur in the absence of detectable mixed cryoglobulinemia.^[30]

Sialadenitis

This condition can result from acute bacterial or viral infection or autoimmune disease, as in Sjögren disease.

Mooren corneal ulcer

Necrolytic acral erythema, a rare disorder, has been linked with HCV infection.^[31]

Cross-reactivity to HCV envelope protein and a corneal antigen appears to be causative. A HCV envelope protein shares the antigenic specificity of this protein, resulting in Mooren ulcer in HCV infection. Other common etiologic causes may occur.

Antiphospholipid syndrome

Immune reactant immunoglobulins with antiphospholipid activity are present.

Autoimmune, not further categorized

Note the following:

Behçet disease: Behçet syndrome is believed to result from an unknown immunologic cause and results in a vasculitis that can cause coagulation and destruction of arteries and veins.
Canities: Illness and disease can affect melanogenesis of the hair.
Prurigo nodularis: A report of HCV infection with prurigo nodularis has been published.^[32]
Lichen planus: Lichen planus is most likely an immunologically mediated reaction.
Sialadenitis: This condition may result from an HCV infection in the salivary gland epithelium and may be a primary disorder of the glands.
Thyroiditis: Destructive inflammation results in early hyperthyroidism. As more of the gland is destroyed, thyroid function normalizes and then becomes subnormal in a hypothyroid picture.
Thrombocytopenia: Thrombocytopenia may be due to a number of causes. These include disorders producing diminished platelet production, altered platelet distribution, and increased platelet destruction. For example, an acute viral infection may produce an acquired defect in diminished platelet production. Medications may give increased platelet destruction. Low platelet counts result in the spontaneous asymptomatic appearance of flat areas of petechiae, purpura, and ecchymosis of the skin.
Vitiligo: A case of hair turning white as a result of HCV infection was reported. HCV could be a risk factor for adult-onset vitiligo in Egyptian patients.^[33]

Tertiary dermatologic disorders (nonspecific disorders manifesting because of organ failure or because disease manifests in the skin)

Persistent viral particles, persistent HCV hepatitis, and transformation are promoted by means already stated.

Dermatologic manifestations of HCV infection in which the cause is uncertain but the association is certain

Proposed etiologic mechanisms for the relationship of chronic hepatitis C infection and PCT include oxidative stress from chronic hepatitis C and other viral infections (HBV and HIV) of hepatocytes that affect uroporphyrin decarboxylase (UDC) function. HIV infection causes increased serum porphyrin levels.^[34]Patients with hereditary PCT and patients with hemochromatosis have sufficient UDC redundant function to prevent the appearance of symptoms. Cytochrome P4501A2, metabolically active iron, chronic hepatitis C, long-term alcohol intake, and estrogens affect the rate of conversion of uroporphyrinogen to uroporphyrin by oxidation in hepatocytes. An increase in delta5-ALA synthetase activity can present excess uroporphyrin to the hepatocyte.

The clinical and immunologic pattern of expression of Sjögren syndrome associated with chronic HCV infection was analyzed.^[35]HCV-associated Sjögren syndrome is indistinguishable from the primary form in most cases. Chronic HCV infection was suggested as an exclusion criterion for the classification of primary Sjögren syndrome because the virus may be implicated in the development of Sjögren syndrome in a specific subset of patients. The phrase "Sjögren syndrome secondary to HCV" was recommended.

Dermatologic manifestations of malignancies associated with chronic hepatitis C disease

Non-Hodgkin lymphoma

A protein amino acid sequence of HCV core protein has homology to a heavy-chain IgG sequence. The viral recognition reaction producing macroglobulin rheumatoid species antibodies may drive the mixed cryoglobulinemia reaction, and it may also cause lymphomagenesis.

Verrucous cell carcinoma of the tongue and OLP with HCV infection and replication

A possible relationship to altered TP53 gene transformation exists with squamous cell carcinoma and hepatoma in cirrhosis.

MALT syndrome

A study concerning the association of HCV and NHLB showed a prevalence of HCV of 37%.^[36]Patients were older, and more patients were female than male. A closer association to immunocytoma was found than to MALT syndrome. Thirteen of 20 cases of immunocytoma had HCV infection, and localization to the orbit and mucosal surfaces was more common. HCV localized to a parotid lymphoma associated with a mixed cryoglobulinemia showed viral proliferation in parotid epithelial cells and not in NHLB cells.^[37]Epstein-Barr virus and herpesvirus type 5 are the other sialotropic viruses not present in the reported cases. Local carcinogenic functions of HCV, effect on the p53 system, immunoregulation, perturbations, and malignant transformation were considered in the etiology of the conditions.

Hepatoma

The ends of HCV RNA are conserved. HCV core protein is a multifunctional protein with a role in apoptosis-antiapoptosis regulation of cell multiplication and tumor control.^[38]The death domain of tumor necrosis factor 1 and the cytoplasmic tail of lymphotoxin beta bind to the core protein. Nuclear factor kappa B (NF-kB) is activated in core peptide-transfected hepatoma cells and in HCV-infected liver tissue. NF-kB activation causes resistance to apoptotic signals in transfected HCV-containing cells. An evasion mechanism of host surveillance by means of NF-kB activation is proposed as one method of viral persistence in the chronic hepatitis C state and in carcinogenesis.

Dermatologic manifestations of treatments for HCV infection

Interferon therapy increases the incidence of immune epiphenomenon and autoimmune disorders.

Frequency

United States

The prevalence of hepatitis C virus (HCV) seropositivity in the United States was 3.9 million persons.^[39]In persons who were seropositive, 65% were aged 30-49 years, and 74% of patients demonstrating positive results were positive for HCV RNA, meaning active viral replication continued to occur. An estimated 2.7 million persons have chronic hepatitis C infection. Genotype 1a occurs in 57% of patients; genotype 1b occurs in 17%. From 1989-1993, the occurrence of HCV decreased 80%, from 50 cases per 100,000 to approximately 28,000 new cases per year. Decreased transfusion-associated disease and a dramatic decrease in intravenous drug use account for this change.

International

Worldwide, 170 million persons have hepatitis C virus (HCV) infection, which represents 3% of the world population.^[40]The prevalence of HCV antibody is less than 3% in developed nations. The prevalences are as high as 70% in highly endemic countries, such as Egypt; the high prevalences relate to specific practices that transmit the disease at specific times in the population.

Race

Race and ethnicity do not relate to hepatitis C virus (HCV). HCV infection is associated with lower economic status, less education, and groups other than whites.

Sex

No sex preponderance occurs with hepatitis C virus (HCV) infection. Sex differences were not significant.^[39]

Age

Of individuals positive for hepatitis C virus (HCV) antibodies, 65% are aged 30-49 years. Younger age at infection often relates to lesser consequences of the infection. Infection is uncommon in persons aged 20 years and younger and is more prevalent in persons older than 40 years.^{[41, 42]}Data suggest the presence of age-related methods of infection, such as nonsterile medical procedures, including vaccination and parenteral drug treatment.^[43]

In August 2012, the Centers for Disease Control and Prevention (CDC) expanded their existing, risk-based testing guidelines to recommend a 1-time blood test for hepatitis C virus (HCV) infection in baby boomers—the generation born between 1945 and 1965, who account for approximately three fourths of all chronic HCV infections in the United States—without prior ascertainment of HCV risk (see Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965).^[15]One-time HCV testing in this population could identify nearly 808,600 additional people with chronic infection. All individuals identified with HCV should be screened and/or managed for alcohol abuse, followed by referral to preventative and/or treatment services, as appropriate.

Prognosis

The prognosis of patients with dermatologic manifestations of hepatitis C virus (HCV) infection rests on the success of therapy for the underlying HCV. At this time, many successes show that eradication of HCV infection is the key factor in the prognosis. The importance of discovering HCV infection magnifies as new therapies develop.

Mortality/morbidity

Although acute hepatitis C virus (HCV) infection is usually mild, chronic hepatitis results in at least 75% of patients.^[22]While liver enzyme levels may be in the reference range, the presence of persistent HCV-RNA levels discloses chronic infection. Biopsy samples of the liver also reveal chronic liver disease in patients. Cirrhosis develops in 20-50% of patients with chronic hepatitis C infection. Liver failure and hepatocellular carcinoma can eventually result. Hepatocellular carcinoma occurred in 11-19% of patients. The risk of cirrhosis and hepatocellular carcinoma doubles in patients who have undergone transfusion.^[44]

Two studies of compensated cirrhosis in the United States and Europe showed that decompensation occurred in 20% of patients and that hepatocellular carcinoma occurred in approximately 10% of patients.^{[45, 46]}The survival rate at 5 and 10 years was 89% and 79%, respectively. The onset of chronic hepatitis C infection early in life often leads to less serious consequences.^{[47, 48]}Hepatitis B virus (HBV) infection, iron overload, and alpha 1-antitrypsin deficiency may play a role in the progression of chronic hepatitis C infection to HCV-related cirrhosis.^{[49, 50]}

Chronic hepatitis C infection and its major sequelae (cirrhosis and hepatoma) are responsible for 8,000-10,000 deaths a year.

Clinical Presentation

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Media Gallery

Cold agglutinin disease indistinguishable from cryoglobulinemia. Courtesy of Walter Reed Army Medical Center Dermatology.
Cryoglobulinemia, palpable purpura, dysproteinemic purpura, and leukocytoclastic vasculitis (small vessel vasculitis). Courtesy of Walter Reed Army Medical Center Dermatology.
Cutis marmorata. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema multiforme, bull's-eye lesions. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema dyschromicum perstans. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema dyschromicum perstans. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema nodosa. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema nodosa. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema multiforme. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema multiforme. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema multiforme. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema multiforme of the oral mucosa. Courtesy of Walter Reed Army Medical Center Dermatology.
Erythema multiforme (Stevens-Johnson syndrome). Courtesy of Walter Reed Army Medical Center Dermatology.
Palmar erythema. Courtesy of Walter Reed Army Medical Center Dermatology.
Granuloma annulare. Courtesy of Walter Reed Army Medical Center Dermatology.
Disseminated superficial (actinic) porokeratosis. Courtesy of Walter Reed Army Medical Center Dermatology.
Disseminated superficial (actinic) porokeratosis. Courtesy of Walter Reed Army Medical Center Dermatology.
Lichen planus. Courtesy of Walter Reed Army Medical Center Dermatology.
Lichen planus. Courtesy of Walter Reed Army Medical Center Dermatology.
Lichen planus. Courtesy of Walter Reed Army Medical Center Dermatology.
Lichen planus (hypertrophic type). Courtesy of Walter Reed Army Medical Center Dermatology.
Lichen planus (oral lesions). Courtesy of Walter Reed Army Medical Center Dermatology.
Lichen planus (volar wrist). Courtesy of Walter Reed Army Medical Center Dermatology.
Lymphoma cutis. Courtesy of Walter Reed Army Medical Center Dermatology.
Henoch-Schönlein purpura. Courtesy of Walter Reed Army Medical Center Dermatology.
Palpable purpura. Courtesy of Walter Reed Army Medical Center Dermatology.
Purpura in hemophilia (factor VIII deficiency). All ecchymoses and bland petechiae are in the differential diagnosis of thrombocytopenic purpuras, including thrombocytopenia secondary to hepatitis C virus in which an autoantibody to platelets is present. Courtesy of Walter Reed Army Medical Center Dermatology.
Progressive pigmented purpuric eruption. Courtesy of Walter Reed Army Medical Center Dermatology.
Progressive pigmented purpura (photo rotated 90°). Courtesy of Walter Reed Army Medical Center Dermatology.
Progressive pigmented purpura (Gougerot-Blum disease). Courtesy of Walter Reed Army Medical Center Dermatology.
Progressive pigmented purpura (Schamberg disease). Courtesy of Walter Reed Army Medical Center Dermatology.
Thrombocytopenic purpura. Courtesy of Walter Reed Army Medical Center Dermatology.
Prurigo nodularis. Courtesy of Walter Reed Army Medical Center Dermatology.
Prurigo nodularis. Courtesy of Walter Reed Army Medical Center Dermatology.
Prurigo nodularis. Courtesy of Walter Reed Army Medical Center Dermatology.
Chronic urticaria. Courtesy of Walter Reed Army Medical Center Dermatology.
Urticaria (secondary to penicillin). Courtesy of Walter Reed Army Medical Center Dermatology.
Nodular vasculitis. Courtesy of Walter Reed Army Medical Center Dermatology.
Henoch-Schönlein purpura, palpable purpura, and leukocytoclastic vasculitis. Courtesy of Walter Reed Army Medical Center Dermatology.
Vitiligo. Courtesy of Walter Reed Army Medical Center Dermatology.
Vitiligo. Courtesy of Walter Reed Army Medical Center Dermatology.
Waldenström hypergammaglobulinemic purpura. Courtesy of Walter Reed Army Medical Center Dermatology.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Arthur P Birnkrant, MD Clinical Instructor, Department of Dermatology, University of Medicine and Dentistry of New Jersey

Arthur P Birnkrant, MD is a member of the following medical societies: American Academy of Dermatology, American Society for MOHS Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: Biogen US (Adjudicator for study entry cutaneous lupus erythematosus); Priovant (Adjudicator for entry into a dermatomyositis study); IQVIA (Serono - adjudicator for a study of cutaneous LE) <br/>Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for these trust accounts for: Stocks held in various trust accounts: Allergen; Amgen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble;; Celgene; Gilead; CVS; Walgreens; Bristol-Myers Squibb.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Craig A Elmets, MD Professor and Chair, Department of Dermatology, Director, Chemoprevention Program Director, Comprehensive Cancer Center, UAB Skin Diseases Research Center, University of Alabama at Birmingham School of Medicine

Craig A Elmets, MD is a member of the following medical societies: American Academy of Dermatology, American Association of Immunologists, American College of Physicians, American Federation for Medical Research, Society for Investigative Dermatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: University of Alabama at Birmingham; University of Alabama Health Services Foundation<br/>Serve(d) as a speaker or a member of a speakers bureau for: Ferndale Laboratories<br/>Received research grant from: NIH, Veterans Administration, California Grape Assn<br/>Received consulting fee from Astellas for review panel membership; Received salary from Massachusetts Medical Society for employment; Received salary from UpToDate for employment. for: Astellas.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Michael Birnkrant, BS, to the development and writing of this article.