What are the other Names for this Condition? (Also known as/Synonyms)

• NUV (Normocomplementemic Urticarial Vasculitis)

What is Normocomplementemic Urticarial Vasculitis? (Definition/Background Information)

• Normocomplementemic Urticarial Vasculitis (NUV) is a less severe form of urticarial vasculitis that is characterized by normal complement protein levels in blood. Urticarial vasculitis (UV) is a rare form of small blood vessel vasculitis that is mostly observed in adults. It is classified into two subtypes - normocomplementemic and hypocomplementemic
• In vasculitis, inflammation of the small blood vessels is observed. It can cause damage to various body organs depending on the region affected, due to decreased blood and oxygen supply to the body region
• Normocomplementemic Urticarial Vasculitis primarily involves skin blood vessels causing predominantly cutaneous symptoms resembling urticaria, which is characterized by red patches on skin, hives, itching sensation, and discoloration of skin. Rarely, mild systemic involvement is seen involving organs, such as the lung and kidney
• The exact cause of Normocomplementemic Urticarial Vasculitis is not understood, but it reportedly immune-mediated. Several autoimmune diseases, viral infections, use of certain medications, and malignancies are associated with the development of this form of vasculitis
• The blood levels of complement proteins correlated with the presenting signs and symptoms may help the healthcare provider diagnose Normocomplementemic Urticarial Vasculitis. Other tests and exams may be performed, such as blood and urine tests, radiological studies, and tissue biopsies, to understand the involvement of various body organs
• An early diagnosis and appropriate treatment of can lead to a good prognosis. Generally, the prognosis of individuals with Normocomplementemic Urticarial Vasculitis is good, since mostly only skin involvement is present

Who gets Normocomplementemic Urticarial Vasculitis? (Age and Sex Distribution)

• Normocomplementemic Urticarial Vasculitis is an uncommon condition that can affect both children and adults. Most of the cases are reported in adults in the 30-40 years’ age range
• Both males and females are affected with a slight female predominance (male-female ratio of 1:2) being noticed
• It is observed worldwide and can affect people of all racial and ethnic backgrounds

What are the Risk Factors for Normocomplementemic Urticarial Vasculitis? (Predisposing Factors)

Normocomplementemic Urticarial Vasculitis is associated with the following factors:

• Autoimmune disorders such as Sjögren's syndrome, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), etc.
• Disorders involving immunoglobulins (proteins in blood) such as IgA and IgM monoclonal gammopathy
• Viral infections that include infectious mononucleosis (mono) and hepatitis B and C viral infections
• Use of certain medications including ACE inhibitors, antibiotics such as penicillin and sulfonamide, and anti-depressants such as fluoxetine and diuretic-thiazides
• Malignancies such as leukemia, among other

In some cases, the risk factors are not clearly evident or present.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Normocomplementemic Urticarial Vasculitis? (Etiology)

• The exact cause of development of Normocomplementemic Urticarial Vasculitis is not known; researchers inform that it may be an immune-mediated condition
• It may develop as a hypersensitivity reaction to certain stimuli, such as an inflammatory condition, infection, or medication use, triggering an abnormal immune reaction in the body

The condition is not transmitted from one individual to another and is not contagious.

What are the Signs and Symptoms of Normocomplementemic Urticarial Vasculitis?

The severity of signs and symptoms of Normocomplementemic Urticarial Vasculitis may vary from one individual to another. In some, it may be mild, resulting in a delayed diagnosis of the condition. In other individuals, it may be severe. The signs and symptoms also depend on the organs affected and the presence of an underlying cause/trigger, if any.

The general signs and symptoms may include:

• Fever
• Skin rashes
• Headaches
• Bloodshot eyes
• Fatigue
• Loss of weight
• Weakness and malaise
• Pain that may affect the chest, back, or abdomen
• Shortness of breath
• Joint pain

The signs and symptoms of Normocomplementemic Urticarial Vasculitis are less severe and mostly confined to the skin. These include:

• Skin eruptions resembling urticaria; urticaria causes weals (red skin sign with itching) and/or angioedema (swelling due to fluid accumulation)
• Itching and burning sensation
• The red plaques may present white center
• Bleeding under skin (petechia) may be noted resulting in dark red discoloration
• Lymph node swelling
• Bleeding on scratching of skin
• Any skin of the body surface may be involved
• The urticaria-like lesions usually last over a day and do not seem to migrate from one region to another
• In many individuals, these abnormal skin symptoms resolve on their own

Following the skin symptoms, mild systemic symptoms that tend to mostly involve the lung and kidney may arise. However, involvement of organs other than the skin is generally minimal to absent. In case of lung and kidney involvement, the following may be seen:

Signs and symptoms related to the lungs and airways (respiratory system):

• Cough that may be persistent
• Blood in cough/sputum (hemoptysis)
• Shortness of breath that gets worse with time
• Difficulty in breathing
• Chest pain
• Heaviness of chest
• Wheezing, exhibiting a high-pitched sound while breathing (stridor)
• Changes to one’s voice
• Hoarseness
• Loss of voice

Signs and symptoms related to the kidney and urinary bladder (genitourinary system):

• Nausea and vomiting
• Unexplained fever
• Night sweats
• Difficulty in urinating; presence of burning sensation
• Pain while urination, frequent urge to urinate
• Presence of blood in the urine
• Feeling of obstruction while urinating
• Inflammation of the bladder (cystitis)
• Sharp pain in the back or lower abdomen that radiates to the groin
• Chronic pain in the pelvis
• Fluid accumulation in the lower legs (pedal edema)
• Increased blood pressure due to kidney problems

How is Normocomplementemic Urticarial Vasculitis Diagnosed?

A diagnosis of Normocomplementemic Urticarial Vasculitis (NUV) will usually depend on the system or organ of the body that is affected and the underlying trigger, if any. The condition is typically diagnosed by measuring the levels of complement proteins (C1q complements) in blood. NUV presents normal blood levels of the complement proteins.

The diagnosis may involve the following tests and examinations:

• Complete physical examination and a thorough medical history
• Assessment of the presenting signs and symptoms

Tests and procedures based on the different body part/organ or system that is affected may include any of the following.

• Blood and urine tests related to overall inflammatory and autoimmune activity:
  • Complete blood count (CBC) with differential: This measures the red blood cell count and hemoglobin levels in blood
  • Erythrocyte sedimentation rate (ESR): ESR is a blood test that can help the healthcare provider identify any inflammatory activity within the body
  • C-reactive protein (CRP) test: This blood test measures the amount of a protein, called C-reactive protein, in blood. It also provides information on the inflammation condition of the body
  • Anti-nuclear antibody (ANA) test: ANA test identifies the antinuclear antibodies within the blood
  • Basic metabolic panel tests
  • Anti-streptolysin O (ASO) titer test, if a streptococcal infection is the suspected trigger
  • Specific antibodies test
  • Protein electrophoresis and immunofixation electrophoresis tests
  • Complement blood test
  • Cryoglobulin blood test
  • HIV antibody blood test
  • Urine tests for protein and presence of blood
  • Urinalysis

Tests and procedures related to the skin and underlying tissue (integumentary system):

• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Punch biopsy of skin for immunofluorescence studies, especially direct immunofluorescence studies. The immunofluorescence deposits can be performed with fluorescein-labeled antibodies against IgG, IgM, IgA, and C3
• Skin biopsy: A skin biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

Tests and procedures related to the lungs and airways (respiratory system):

• Arterial blood gas analysis
• Pulmonary function test (PFT)
• Imaging studies that may include:
  • Chest X-ray
  • CT scan of the chest
  • MRI scan of the lungs
  • Pulmonary angiogram
• Sputum cytology: This procedure involves the collection of mucus (sputum), coughed-up by the patient, which is then examined in a laboratory by a pathologist

A tissue biopsy refers to a medical procedure that involves the removal of cells or tissues, which are then examined by a pathologist. This can help establish a definitive diagnosis. The different biopsy procedures may include the following:

• Bronchoscopy: During bronchoscopy, a special medical instrument called a bronchoscope is inserted through the nose and into the lungs to collect small tissue samples. These samples are then examined by a pathologist, after the tissues are processed, in an anatomic pathology laboratory
• Thoracoscopy: During thoracoscopy, a surgical scalpel is used to make very tiny incisions into the chest wall. A medical instrument called a thoracoscope is then inserted into the chest, in order to examine and remove tissue from the chest wall, which are then examined further
• Thoracotomy: Thoracotomy is a surgical invasive procedure with special medical instruments to open-up the chest. This allows a physician to remove tissue from the chest wall or the surrounding lymph nodes of the lungs. A pathologist will then examine these samples under a microscope after processing the tissue in a laboratory
• Fine needle aspiration biopsy (FNAB): During fine needle aspiration biopsy, a device called a cannula is used to extract tissue or fluid from the lungs, or surrounding lymph nodes. These are then examined in an anatomic pathology laboratory, in order to determine any signs of abnormality. Nevertheless, FNAB is not a preferred method for the biopsy of lung tissue
• Autofluorescence bronchoscopy: It is a bronchoscopic procedure in which a bronchoscope is inserted through the nose and into the lungs and measure light from abnormal precancerous tissue. Samples are collected for further examination by a pathologist

Note: Procedures, such as a bronchoscopy, thoracoscopy, thoracotomy, and autofluorescence bronchoscopy, do not always result in a tissue biopsy.

Tissue biopsy from the affected lung:

• A biopsy of the tissue is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis

Tests and procedures related to the kidney and urinary bladder (genitourinary system):

• Diagnostic tests may include the following:
  • Urinalysis
  • Blood tests including blood urea nitrogen (BUN) and creatinine levels
  • Kidney function tests
• Radiological studies that may include:
  • Abdominal X-ray
  • CT scan of the abdomen
  • Ultrasound scan of the kidneys
  • MRI scan of the kidney
  • Intravenous pyelogram (IVP): A dye is injected into the blood vessels and the image of kidney structure is obtained
  • Angiography of the abdominal region
• Ureteroscopy: Endoscopic study of the upper urinary tract using an endoscope inserted through the urethra
• Cystoscopy: During a cystoscopy, a narrow tube called a cystoscope is inserted to look directly into the bladder. A local anesthetic is usually administered, in order to make the examination more comfortable

Invasive diagnostic procedures such as:

• Laparoscopy: A special device is inserted through a small hole into the abdomen, to visually examine it. If necessary, a tissue sample is obtained for further analysis. Exploration of the abdomen using a laparoscope is called ‘exploratory laparoscopy’
• Laparotomy: The abdomen is opened through an incision for examination, and if required, a biopsy sample obtained. Exploration of the abdomen using laparotomy procedure is called ‘exploratory laparotomy’

Although the above modalities can be used to make the initial diagnosis, a tissue biopsy may be required to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways, and they include:

• Fine needle aspiration (FNA) biopsy: An FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the affected region. Hence, an FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of kidney
• Open biopsy of kidney

A tissue biopsy is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis.

• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation.
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely electron microscopic studies to assist in the diagnosis

Other diagnostic examinations may be performed based on the affected region/part of the body and the nature of the underlying condition.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Normocomplementemic Urticarial Vasculitis?

The complications of Normocomplementemic Urticarial Vasculitis depend on the organs affected, severity of the signs and symptoms, and one’s response to treatment. Generally, severe complications are not observed.

Complications associated with the skin and underlying tissue (integumentary system) may include:

• Emotional stress due to cosmetic concerns
• Bleeding and ulceration
• Severe pain and itchiness of skin leading to acute discomfort and irritation, including sleep disruption
• The lesions may occasionally develop bacterial or fungal infections
• Permanent scarring

Complications associated with the lungs and airways (respiratory system) may include:

• Severe chest pain
• Severe obstruction of the airways causing acute breathing difficulties
• Pleural effusion (fluid in the chest)
• Chronic obstructive pulmonary disease (COPD)
• Irreversible lung damage
• Development of pneumothorax (collapsed lung)
• Respiratory failure
• Decreased quality of life

Complications associated with the kidney and urinary bladder (genitourinary system) may include:

• Severe pain in the back or lower part of the abdomen
• Obstruction of the urinary bladder
• Blockage of the urinary tract may lead to kidney damage
• Hydronephrosis of kidneys (swollen kidneys)
• Erectile dysfunction
• Urinary incontinence (involuntary dripping or leakage of urine)
• Severe cases may result in kidney damage and kidney failure

How is Normocomplementemic Urticarial Vasculitis Treated?

The treatment of Normocomplementemic Urticarial Vasculitis depends upon a variety of factors including:

• Severity of the signs and symptoms
• Regions of the body affected and the level of functioning of the affected organs
• Overall health status of the individual and his/her age
• Underlying condition, if any

The main treatment of Normocomplementemic Urticarial Vasculitis includes treating the underlying cause. If a clearly identifiable cause is not known, then the primary role of treatment is to reduce inflammation. Often, a multidisciplinary team of specialists that include general practitioners, rheumatologists, neurologists, pulmonologists, cardiovascular experts, nephrologists, dermatologists, ophthalmologists, among others, may be involved in the treatment.

The treatment methods for the condition may include:

• Symptomatic treatment for systemic conditions may include use of the following medications:
  • For infections, antiviral agents and antibiotics such as dapsone
  • Antimalarial medications such as hydroxychloroquine
  • Pain-relievers
  • Antihistamines and non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, and indomethacin, for pain and swelling
  • Wound care for ulceration
  • Corticosteroid therapy, such as using oral prednisone, for severe and long-term condition
• Immunosuppressive medications: It is generally not necessary to treat the condition
• Biologic agents using specific monoclonal antibodies to reduce inflammation
• In cases with severe symptoms, or when the affected individuals do not respond to the above-mentioned treatments, plasma exchange (plasmapheresis) or intravenous immunoglobulin (IVIG) therapy may be considered

The treatment also depends on whether there are recurring episodes of the condition. The goal of the treatment is to control the inflammation in order to achieve remission (a state where no signs and symptoms are noted) and maintenance therapy to prevent episodes of relapses.

How can Normocomplementemic Urticarial Vasculitis be Prevented?

Currently, there are no methods available to prevent Normocomplementemic Urticarial Vasculitis. An early diagnosis and prompt treatment can help decrease the burden of the condition.

• Undertaking early and appropriate treatment of the underlying infection or condition (potential risk factors) may help in lowering one’s risk for the condition and is an important consideration
• Treating and managing the underlying condition that triggered the initial episode helps in preventing subsequent episodes
• Maintaining a healthy lifestyle with good eating habits, adequate physical activities, and avoidance of smoking or drinking is beneficial
• Ensuring that individuals, especially children, are up-to-date on their vaccinations is important
• Patients are required to be vigilant during the remission period and report any new symptoms promptly to the healthcare provider

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory, due to the possibility of recurrence/relapse. Often several years of active vigilance is necessary.

What is the Prognosis of Normocomplementemic Urticarial Vasculitis? (Outcomes/Resolutions)

• The prognosis of Normocomplementemic Urticarial Vasculitis (NUV) depends upon a variety of factors including the:
  • Severity of the condition; degree of damage to the vital organs and body systems
  • Age and overall health of the individual
  • Underlying triggering factor
  • One’s response to treatment: Individuals who respond to treatment usually have a better prognosis than those who do not respond well to treatment
  • Whether it is an initial episode or a recurring episode
• Normocomplementemic Urticarial Vasculitis is usually mild and systemic involvement is minimal to absent; it is also known to be self-resolving, though some resolve slowly. The skin lesions are also known to get better and recede following appropriate treatment, sometimes after a few years
• Nevertheless, urticarial vasculitis can be a chronic condition with relapses/recurrences and periods of remission. It is reported that 80% of the individuals respond well to corticosteroid therapy for the skin symptoms

Even with treatment, NUV can relapse. If blood in cough or blood in urine is observed, then it is extremely important to contact the healthcare provider right away.

Additional and Relevant Useful Information for Normocomplementemic Urticarial Vasculitis:

The following article link will help you understand other Vein & Vascular Health:

https://www.dovemed.com/health-topics/vein-and-vascular-center/