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Urticarial Vasculitis

Urticarial vasculitis refers to an inflammation of skin capillaries that causes dermatological symptoms. Urticarial vasculitis may be part of a systemic condition that manifests in form of additional symptoms.


Presentation

While UV is primarily a dermatological finding, patients may present a variety of systemic symptoms that may either result from idiopathic UV, a possible immune complex disease, or from the underlying disorder.

Urticaria may affect any part of the body. Allergic urticaria is transient and usually subsides within minutes or hours. Urticaria due to UV, however, typically persists for more than 24 hours, possibly even for several days. While the former is generally associated with pruritus, patients suffering from UV more frequently experience a burning sensation and pain. Angioedema is common. When wheals finally resolve, palpable purpura may be developed. In fact, diascopic examination of papules may reveal central petechia long before hemorrhages become visible to the naked eye. Hemorrhages fade centrally and ultimately completely, but hyperpigmented skin areas may remain.

With regards to systemic symptoms, articular complaints are most common. However, several organ systems may be affected in some cases and justify diagnosis of hypocomplementemic urticarial vasculitis syndrome [6] [7] [8]. In detail, the following may be detected:

Thyroid Nodule
  • Symptoms included submandibular gland swelling, lymphadenopathy, interstitial nephritis, and a thyroid nodule.[ncbi.nlm.nih.gov]
Respiratory Disorders
  • Respiratory disorders, namely tracheal stenosis and chronic obstructive pulmonary disease, which cause dyspnea, cough, hemoptysis and other symptoms, may be associated with UV and may be life-threatening.[symptoma.com]
Regurgitation
  • […] leading to progressive deformity of the joints of the hands and feet (without loss of cartilage or erosion of bone), persistent urticaria exacerbated by cold and accompanied by hypocomplementemia and progressive cardiac valvular disease with mitral valve regurgitation[ncbi.nlm.nih.gov]
  • In addition to urticarial cutaneous lesions, he experienced polyarthralgia and arthritis that resulted in progressive deformity of the joints of both hands, cardiac valvulopathy with mitral, tricuspid, and aortic regurgitation, and intermittent neck swelling[jmedicalcasereports.biomedcentral.com]
Dysphagia
  • Abstract A 55 years post menopausal lady presented with puffiness of face, and a pruritic urticarial rash over face and upper trunk of one week duration with accompanying dysphagia.[ncbi.nlm.nih.gov]
Vascular Disease
  • Diseases Cardiovascular Diseases Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs[clinicaltrials.gov]
Muscle Weakness
  • During the course of her hospitalization, she was also found to have profound proximal muscle weakness in both upper and lower limbs associated with raised creatinine kinase levels.[ncbi.nlm.nih.gov]
Proximal Muscle Weakness
  • During the course of her hospitalization, she was also found to have profound proximal muscle weakness in both upper and lower limbs associated with raised creatinine kinase levels.[ncbi.nlm.nih.gov]
Urticaria
  • ) and Schnitzler's Syndrome, both rare multisystem forms that may masquerade as common urticaria.[ncbi.nlm.nih.gov]
  • Urticaria may affect any part of the body. Allergic urticaria is transient and usually subsides within minutes or hours. Urticaria due to UV, however, typically persists for more than 24 hours, possibly even for several days.[symptoma.com]
Chronic Urticaria
  • RESULTS: Patients with active chronic urticaria had the highest serum levels of D-dimer (p CONCLUSIONS: Patients with active chronic urticaria have higher serum levels of D-dimer, when compared to patients with chronic urticaria under remission and patients[ncbi.nlm.nih.gov]
  • From Wikidata Jump to navigation Jump to search No description defined Chronic urticaria as a manifestation of venulitis Hypocomplementemic urticarial vasculitis syndrome Hypocomplementemic vasculitis Unusual lupus-like syndrome Mac Duffie syndrome Anti-C1q[wikidata.org]
Cutis Laxa
  • In nearly 50% of cases, erythematous plaques present before the onset of cutis laxa. Separately, urticarial vasculitis and systemic lupus erythematosus have been linked to cutis laxa acquisita.[ncbi.nlm.nih.gov]
  • A case with rapidly progressing acquired cutis laxa following involvement of the skin areas with lesions of NUV was reported [ 92 ].[intechopen.com]
Lethargy
  • Side-effects are common and include lethargy, headaches, methaemoglobinaemia and haemolysis. Severe adverse effects are rare but the dapsone hypersensitivity syndrome is well recognized.[ncbi.nlm.nih.gov]

Workup

Patients presenting with persistent urticaria are suspicious for UV. A skin biopsy, ideally taken of recent lesions, is required to confirm the latter. Histopathological analysis will reveal leukocytoclastic vasculitis, i.e., leukocyte-mediated inflammation and destruction of dermatic vessels. Perivascular immune cell infiltration is clearly visible and mainly affects postcapillary venules. Neutrophil granulocytes predominate the picture, but considerable numbers of lymphocytes may be detected in samples taken in advanced stages of the disease. If possible, immunofluorescence should be applied to visualize immune complexes, complement and fibrin deposition [7].

Additional diagnostic measures are required to distinguish between idiopathic and other forms of UV and to assess the extent of the disease. While the patient's medical history may indicate possible serum sickness or drug-induced UV, laboratory analyses of blood samples are carried out to check for autoantibodies pointing at autoimmune disorders and antibodies against viral pathogens. Blood chemistry is a valuable tool to evaluate the condition of liver, kidneys and other organ systems. Involvement of the respiratory tract may be revised with radiographic imaging and pulmonary function tests.

Ground Glass Appearance
  • High Resolution Computed Tomography of the chest revealed diffuse ground-glass appearance, increased interstitial density.[ncbi.nlm.nih.gov]

Treatment

Severity of symptoms and systemic involvement are the main criteria to be considered when choosing a therapeutic scheme. There are no official guidelines for UV treatment because no controlled clinical trials have been performed. Any recommendations given are based on experience with certain compounds in a minor number of patients.

Urticaria and associated symptoms such as pruritus, burning and possibly pain are treated with antihistamines. In very mild cases, antihistamines may be sufficient to control the disease. However, this hardly applies to patients with systemic symptoms.

Immunosuppressants, mainly corticosteroids, are administered to reduce vascular inflammation and a possibly underlying immune reaction of type III hypersensitivity. Due to the usual extent of lesions, they are administered systemically rather than topically. Of course, corticosteroids will also act on other organs, but in order to decrease joint inflammation, non-steroidal anti-inflammatory drugs have been proven more efficient. Naproxen (500 mg tid) and ibuprofen (up to 800 mg qid) are most often used and promise good results in a significant share of patients.

Dapsone, an antirheumatic and antimicrobial agent, has been successfully applied to treat UV [12]. Some reports indicate that dapsone is particularly helpful to limit UV-associated pulmonary damage. Daily doses of 50 to 100 mg should be administered.

Furthermore, hydroxychloroquine, a well known antimalarial drug with antirheumatic properties, and colchicine, which presumably inhibits chemotactic attraction of leukocytes to dermatic vessels, may be prescribed to UV patients. Both drugs are used less frequently than the aforementioned compounds. Often, they are administered supplementarily to patients who do not present a satisfying response to corticosteroid or dapsone treatment.

If neither of these drugs is effective to improve the patient's condition, more potent immunosuppressive compounds and cytostatics may be indicated. In this line, azathioprine, cyclosporin A, mycophenolate, cyclophosphamide and methotrexate may be applied. In some cases, patients may benefit particularly from combined therapies.

Prognosis

Non-hypocomplementemic, idiopathic UV is usually benign and heals after years without leaving long-term consequences. If an underlying disease can be identified, prognosis generally depends on curability of the former. Low levels of serum complement and systemic involvement are unfavorable prognostic factors and are associated with significant morbidity and mortality.

Etiology

The histopathological finding of leukocytoclastic vasculitis characteristic for UV has been related to a variety of pathological conditions [4]:

Nevertheless, many cases of UV are still deemed idiopathic. The latter are commonly less severe and tend to have a better outcome.

Epidemiology

The annual incidence of leukocytoclastic vasculitis has been estimated to be about 5 per 100,000 individuals [5]. A small share of those cases corresponds to UV.

It has been estimated that one out of 50 patients presenting with urticaria to any physician or hospital may suffer from UV.

No differences regarding race and gender have been reported.

While some studies report an increase of leukocytoclastic vasculitis incidence with age, others describe considerable shares of UV cases to occur in adolescents [1] [5].

Sex distribution
Age distribution

Pathophysiology

According to current knowledge, deposition of immune complexes in skin vessels triggers leukocytoclastic vasculitis and subsequent UV. This is precisely the mechanism behind distinct forms of type III hypersensitivity and indeed, SLE, serum sickness, hepatitis B an C, all frequently associated with UV, may be considered immune complex diseases. Some underlying diseases have not yet been related to type III hypersensitivity reactions. However, histopathological analyses of skin biopsies and the fact that plasmapheresis relieves UV symptoms argue strongly for this hypothesis.

Immune complex diseases are often accompanied by increased consumption of complement factors. Immune complexes are able to activate the classical complement pathway by binding C1q and triggering the catalytic cascade. Some steps downstream of C1q binding, C3a and C5a are released. These factors induce mast cell degranulation and may cause urticaria. C3a and C5a are also chemotactic agents and attract leukocytes.

Immune complexes preferentially deposit in small vessels, but also in glomeruli and joints. Therefore, UV patients with systemic involvement often present with glomerulonephritis and arthritis. The former results in renal functional impairment, proteinuria and possibly hematuria. Loss of protein leads to hypoalbuminemia and formation of generalized edema. Arthritis mainly provokes arthralgia and limitation of joint movements.

Additionally, intrapulmonary deposition of immune complexes may trigger respiratory symptoms.

Prevention

No preventive measures can be recommended.

Summary

Multiple papules and pruritus are characteristic for urticaria and this condition constitutes one of the most frequently observed dermatological findings. It may be triggered by a variety of causes, but the majority of patients presenting with itchy hives suffers from allergic urticaria. Nevertheless, urticarial vasculitis (UV) should be considered as a differential diagnosis because it may manifest with very similar symptoms. However, contrary to allergic urticaria, burning skin lesions due to UV persist for more than 24 hours [1]. After wheals subside, palpable purpura may develop. These hemorrhages may first clear centrally before fading and in some cases, areas of hyperpigmentation remain.

Diagnosis of UV requires histopathological analysis of a skin biopsy. The most characteristic finding is leukocytoclastic vasculitis, i.e., inflammation and degradation of skin vessels mediated by white blood cells [2]. A variety of pathological conditions has been proposed to trigger UV, e.g., autoimmune disorders, infectious diseases, drug administration and malignancies. Many cases of UV are deemed idiopathic because no underlying disorder can be identified. Of note, laboratory analyses of blood samples often reveal reduced levels of complement. Such patients may be diagnosed with hypocomplementemic UV. Its etiology is not fully understood but decreased serum complement concentrations may result from excess consumption in a type III hypersensitivity reaction that results in vascular damage. Possibly, similar pathophysiological events occur in non-hypocomplementemic UV. These patients usually suffer from less severe forms of UV which may explain why depletion of complement factors is less prominent [3].

Therapy should be adjusted to the underlying disease, if it can be identified. Immunosuppresants, non-steroidal anti-inflammatory drugs and antihistamines are often employed to treat UV. Potent immunosuppression and application of cytostatic agents may be required in severe cases and in patients who don't respond to less aggressive therapy.

Patient Information

Urticaria is the medical term for wheals; it most commonly indicates an allergic reaction or contact to certain animals or plants, nettle for instance. However, in some cases, urticaria may be triggered by an inflammation of small blood vessels of the skin. This condition is designated urticaria vascularis (UV).

Causes

UV may be caused by distinct primary diseases:

However, in many cases, no precise cause can be identified. These are deemed idiopathic UV.

Symptoms

Dermatological symptoms are most characteristic for UV. Itching, sometimes burning wheals develop on any part of the body. Contrary to those caused by an allergic reaction or contact to animals or plants, they persist for more than 24 hours, sometimes for days. When these hives finally subside, skin hemorrhages may develop. They fade slowly and hyperpigmented areas may still be visible after hemorrhages disappeared.

The immune reaction triggering UV is, however, not limited to the skin. Therefore, UV patients may also present joint pain and arthritis, renal disorders that may be indicated by bloody in the urine, abdominal pain, vomiting, diarrhea and breathing difficulties.

Diagnosis

UV itself is diagnosed after histopathological analysis of a skin biopsy. Here, characteristic findings are inflammation and destruction of small skin vessels.

Patients may subsequently be submitted to a variety of diagnostic measures in order to reveal the underlying disease. Blood samples will be analyzed, radiographic imaging and pulmonary function tests may be carried out. Depending on the results of these exams, the physician will decide how to proceed further.

Treatment

Wheal formation and the associated sensation of itching and burning are diminished with antihistamines. In mild cases, this treatment may be sufficient. However, most UV patients will require further immunosuppressive treatment to reduce the inflammation of skin vessels, joints, kidneys and other tissues. Corticosteroids are most often employed to this end. A significant share of patients also benefits from antirheumatic therapy. More potent drugs are reserved for severe cases and systemic involvement.

References

Article

  1. Loricera J, Calvo-Rio V, Mata C, et al. Urticarial vasculitis in northern Spain: clinical study of 21 cases. Medicine (Baltimore). 2014; 93(1):53-60.
  2. Davis MD, Brewer JD. Urticarial vasculitis and hypocomplementemic urticarial vasculitis syndrome. Immunol Allergy Clin North Am. 2004; 24(2):183-213, vi.
  3. Venzor J, Lee WL, Huston DP. Urticarial vasculitis. Clin Rev Allergy Immunol. 2002; 23(2):201-216.
  4. Moreno-Suarez F, Pulpillo-Ruiz A, Zulueta Dorado T, Conejo-Mir Sanchez J. Urticarial vasculitis: a retrospective study of 15 cases. Actas Dermosifiliogr. 2013; 104(7):579-585.
  5. Arora A, Wetter DA, Gonzalez-Santiago TM, Davis MD, Lohse CM. Incidence of leukocytoclastic vasculitis, 1996 to 2010: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2014; 89(11):1515-1524.
  6. Balsam L, Karim M, Miller F, Rubinstein S. Crescentic glomerulonephritis associated with hypocomplementemic urticarial vasculitis syndrome. Am J Kidney Dis. 2008; 52(6):1168-1173.
  7. Mehregan DR, Hall MJ, Gibson LE. Urticarial vasculitis: a histopathologic and clinical review of 72 cases. J Am Acad Dermatol. 1992; 26(3 Pt 2):441-448.
  8. Chen HJ, Bloch KJ. Hypocomplementemic urticarial vasculitis, jaccoud's arthropathy, valvular heart disease, and reversible tracheal stenosis: a surfeit of syndromes. J Rheumatol. 2001; 28(2):383-386.
  9. Park C, Choi SW, Kim M, Park J, Lee JS, Chung HC. Membranoproliferative glomerulonephritis presenting as arthropathy and cardiac valvulopathy in hypocomplementemic urticarial vasculitis: a case report. J Med Case Rep. 2014; 8:352.
  10. Jones MD, Tsou E, Lack E, Cupps TR. Pulmonary disease in systemic urticarial vasculitis: the role of bronchoalveolar lavage. Am J Med. 1990; 88(4):431-434.
  11. Jachiet M, Flageul B, Deroux A, et al. The clinical spectrum and therapeutic management of hypocomplementemic urticarial vasculitis: data from a French nationwide study of fifty-seven patients. Arthritis Rheumatol. 2015; 67(2):527-534.
  12. Nishijima C, Hatta N, Inaoki M, Sakai H, Takehara K. Urticarial vasculitis in systemic lupus erythematosus: fair response to prednisolone/dapsone and persistent hypocomplementemia. Eur J Dermatol. 1999; 9(1):54-56.

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Last updated: 2019-07-11 20:59