A detailed history is important to elicit any recent medications, any risk of hepatitis infection, or any recent diagnosis with a connective tissue disorder such as systemic lupus erythematosus (SLE). A thorough physical exam is needed as usual.

- Lab tests. Basic lab tests may include a CBC, chem-7 (look for creatinine), muscle enzyme, liver function tests, ESR, hepatitis seroloties, urinalysis, CXR, and EKG. Additional, more specific tests include:

- Antinuclear antibody (ANA) test can detect an underlying connective tissue disorder, especially SLE

- Complement levels that are low can suggest mixed cryoglobulinemia, hepatitis C infection, and SLE, but not most other vasculitides.

- Antineutrophil cytoplasmic antibody (ANCA) may highly suggest granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, or drug-induced vasculitis, but is not diagnostic.

- Electromyography. It is useful if a systemic vasculitis is suspected and neuromuscular symptoms are present.

- Arteriography. Arteriograms are helpful in vasculitis affecting the large and medium vessels but not helpful in small vessel vasculitis. Angiograms of mesenteri or renal arteries in polyarteritis nodosa may show aneurysms, occlusions, and vascular wall abnormalities. Arteriography are not diagnostic in itself if other accessible areas for biopsy are present. However, in Takayasu's arteritis, where the aorta may be involved, it is unlikely a biopsy will be successful and angiography can be diagnostic.

- Tissue biopsy. This is the gold standard of diagnosis when biopsy is taken from the most involved area.

The diagnostic testing for vasculitis should be guided by the patient's history and physical exam. The clinician should ask about the duration, onset, and presence any associated symptoms such as weight loss or fatigue (that would indicate a systemic cause). It is important to distinguish between IgA and non-IgA vasculitis. IgA vasculitis is more likely to present with abdominal pain, bloody urine, and joint pain. In the case that the cause is not obvious, a reasonable initial workup would include a complete blood count, urinalysis, basic metabolic panel, fecal occult blood testing, erythrocyte sedimentation rate (ESR), and C-reactive protein level. Small vessel cutaneous vasculitis is a diagnosis of exclusion and requires ruling out systemic causes of the skin findings. Skin biopsy (punch or excisional) is the most definitive diagnostic test and should be performed with 48 hours of appearance of the vasculitis. A skin biopsy will be able to determine if the clinical findings are truly due to a vasculitis or due to some other cause.

No specific lab tests exist for diagnosing polyarteritis nodosa. Diagnosis is generally based on the physical examination and a few laboratory studies that help confirm the diagnosis:

A patient is said to have polyarteritis nodosa if he or she has three of the 10 signs known as the 1990 American College of Rheumatology (ACR) criteria, when a radiographic or pathological diagnosis of vasculitis is made:

In polyarteritis nodosa, small aneurysms are strung like the beads of a rosary, therefore making "rosary sign" an important diagnostic feature of the vasculitis. The 1990 ACR criteria were designed for classification purposes only. Nevertheless, their good discriminatory performances, indicated by the initial ACR analysis, suggested their potential usefulness for diagnostic purposes as well. Subsequent studies did not confirm their diagnostic utility, demonstrating a significant dependence of their discriminative abilities on the prevalence of the various vasculitides in the analyzed populations. Recently, an original study, combining the analysis of more than 100 items used to describe patients' characteristics in a large sample of vasculitides with a computer simulation technique designed to test the potential diagnostic utility of the various criteria, proposed a set of eight positively or negatively discriminating items to be used as a screening tool for diagnosis in patients suspected of systemic vasculitis.

Treatment is targeted to the underlying cause. However, most vasculitis in general are treated with steroids (e.g. methylprednisolone) because the underlying cause of the vasculitis is due to hyperactive immunological damage. Immunosuppressants such as cyclophosphamide and azathioprine may also be given.

A systematic review of antineutrophil cytoplasmic antibody (ANCA) positive vasculitis identified best treatments depending on whether the goal is to induce remission or maintenance and depending on severity of the vasculitis.

For the diagnosis of lupus 4 out of 11 signs must be present.

Testing may include:

- Antinuclear antibody (ANA)

- CBC with differential

- Chest x-ray

- Serum creatinine

- Urinalysis

Treatment should be directed towards the specific underlying cause of the vasculitis. If no underlying cause is found and the vasculitis is truly limited to the skin then treatment is primarily supportive. Such treatment involves measures such as leg elevation, stockings, and topical steroids to relieve itching/burning. If the vasculitis does not self-resolve within 3–4 weeks, more aggressive treatment may be warranted. Oral colchicine or dapsone are often used for this purpose. If rapid control of symptoms is needed, a short course of high-dose oral steroids may be given. Immunosuppressive agents such as methotrexate and azathioprine may be used in truly refractory cases not responsive to colchicine or dapsone.

Lupus erythematosus may manifest as systemic disease or in a purely cutaneous form also known as "incomplete lupus erythematosus". Lupus has four main types:

- systemic

- discoid

- drug-induced

- neonatal

Of these, systemic lupus erythematosus (also known as SLE) is the most common and serious form.

A more thorough categorization of lupus includes the following types:

- acute cutaneous lupus erythematosus

- subacute cutaneous lupus erythematosus

- discoid lupus erythematosus (chronic cutaneous)

- childhood discoid lupus erythematosus

- generalized discoid lupus erythematosus

- localized discoid lupus erythematosus

- chilblain lupus erythematosus (Hutchinson)

- lupus erythematosus-lichen planus overlap syndrome

- lupus erythematosus panniculitis (lupus erythematosus profundus)

- tumid lupus erythematosus

- verrucous lupus erythematosus (hypertrophic lupus erythematosus)

- cutaneous lupus mucinosis

- complement deficiency syndromes

- drug-induced lupus erythematosus

- neonatal lupus erythematosus

- systemic lupus erythematosus

Treatment involves medications to suppress the immune system, including prednisone and cyclophosphamide. In some cases, methotrexate or leflunomide may be helpful. Some patients have also noticed a remission phase when a four-dose infusion of rituximab is used before the leflunomide treatment is begun. Therapy results in remissions or cures in 90% of cases. Untreated, the disease is fatal in most cases. The most serious associated conditions generally involve the kidneys and gastrointestinal tract. A fatal course usually involves gastrointestinal bleeding, infection, myocardial infarction, and/or kidney failure.

In case of remission, about 60% experience relapse within five years. In cases caused by hepatitis B virus, however, recurrence rate is only around 6%.

IgG4-related skin disease is the recommended name for skin manifestations in IgG4-related disease (IgG4-RD). Multiple different skin manifestations have been described.

Although a clear understanding of the various skin lesions in IgG4-related disease is a work in progress, skin lesions have been classified into subtypes based on documented cases:

- Angiolymphoid hyperplasia with eosinophilia (or lesions that mimic it) and cutaneous pseudolymphoma

- Cutaneous plasmacytosis

- Eyelid swelling (as part of Mikulicz's disease)

- Psoriasis-like eruptions

- Unspecified maculopapular or erythematous eruptions

- Hypergammaglobulinemic purpura and urticarial vasculitis

- Impaired blood supply to fingers or toes, leading to Raynaud's phenomenon or gangrene

Note:

In addition, Wells syndrome has also been reported in a case of IgG4-related disease.

The diagnosis is confirmed by a skin biopsy and a positive culture for acid-fast bacilli. A PPD test may also result positive.

Subcutaneous sarcoidosis (also known as "Darier–Roussy disease" and "Darier-Roussy sarcoid") is a cutaneous condition characterized by numerous 0.5- to 0.3-cm deep-seated nodules on the trunk and extremities.

Scar sarcoid (also known as "Sarcoidosis in scars") is a cutaneous condition characterized by infiltration and elevation of tattoos and old flat scars due to sarcoidosis.

Mucosal sarcoidosis is a cutaneous condition characterized by pinhead-sized papules that may be grouped and fused together to form a flat plaque.

Erythrodermic sarcoidosis is a cutaneous condition and very rare form of sarcoidosis.

Acute cutaneous lupus erythematosus is a cutaneous condition characterized by a bilateral malar rash (also known as a "butterfly rash") and lesions that tend to be transient, and that follow sun exposure.

Sarcoidosis involves the skin in about 25% of patients. The most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. Treatment is not required, since the lesions usually resolve spontaneously in two to four weeks. Although it may be disfiguring, cutaneous sarcoidosis rarely causes major problems.

The differential diagnosis for OLP includes:

- Other oral vesiculo-ulcerative conditions such as Pemphigus vulgaris and Benign mucous membrane pemphigoid

- Lupus erythematosus, with lesions more commonly occur on the palate and appear as centrally ulcerated or erythematous with radiating white striae. In contrast, OLP and lichenoid reactions rarely occur on the palate, and the striae are randomly arranged rather than radial.

- Chronic ulcerative stomatitis

- Frictional keratosis and Morsicatio buccarum (chronic cheek biting)

- Oral leukoplakia

- Oral candidiasis

Lichen planus has a unique microscopic appearance that is similar between cutaneous, mucosal and oral. A Periodic acid-Schiff stain of the biopsy may be used to visualise the specimen. Histological features seen include:

- thickening of the stratum corneum both with nuclei present (parakeratosis) and without (orthokeratosis). Parakeratosis is more common in oral variants of lichen planus.

- thickening of the stratum granulosum

- thickening of the stratum spinosum (acanthosis) with formation of colloid bodies (also known as Civatte bodies, Sabouraud bodies) that may stretch down to the lamina propria.

- liquefactive degeneration of the stratum basale, with separation from the underlying lamina propria, as a result of desmosome loss, creating small spaces (Max Joseph spaces).

- Infiltration of T cells in a band-like pattern into the dermis "hugging" the basal layer.

- Development of a "saw-tooth" appearance of the rete pegs, which is much more common in non-oral forms of lichen planus.

Cerebral angiography and magnetic resonance imaging, family medical history, symptoms, a complete physical examination, and ultimately biopsy of the brain, are often required for the diagnosis. Also, many lab tests must be done for the diagnosis; tests may reveal anemia (a shortage of red blood cells), a high white blood cell count, a high platelet count, allergic reactions, immune complexes, antibodies (tools the body uses to fight off threats) and elevation of inflammatory markers. Another crucial part in the diagnosis of cerebral vasculitis is the use of imaging techniques. Techniques such as conventional digital subtraction angiography (DSA) and magnetic resonance imaging (MRI) are used to find and monitor cerebral involvement.

Therapy for cutaneous tuberculosis is the same as for systemic tuberculosis, and usually consists of a 4-drug regimen, i.e., isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin.

Treatment is first with many different high-dose steroids, namely glucocorticoids. Then, if symptoms do not improve additional immunosuppression such as cyclophosphamide are added to decrease the immune system's attack on the body's own tissues. Cerebral vasculitis is a very rare condition that is difficult to diagnose, and as a result there are significant variations in the way it is diagnosed and treated.

Primary cutaneous amyloidosis is a form of amyloidosis associated with oncostatin M receptor. This type of amyloidosis has been divided into the following types:

- Macular amyloidosis is a cutaneous condition characterized by itchy, brown, rippled macules usually located on the interscapular region of the back. Combined cases of lichen and macular amyloidosis are termed biphasic amyloidosis, and provide support to the theory that these two variants of amyloidosis exist on the same disease spectrum.

- Lichen amyloidosis is a cutaneous condition characterized by the appearance of occasionally itchy lichenoid papules, typically appearing bilaterally on the shins.

- Nodular amyloidosis is a rare cutaneous condition characterized by nodules that involve the acral areas.

The following types of CVID have been identified, and correspond to mutations in different gene segments.

Jessner lymphocytic infiltrate of the skin is a cutaneous condition characterized by a persistent papular and plaque-like skin eruption which can occur on the neck, face and back and may re-occur. This is an uncommon skin disease and is a benign collection of lymph cells. Its cause is not known and can be hereditary. It is named for Max Jessner. It is thought to be equivalent to lupus erythematosus tumidus.

It can occur as the result of ACE inhibitors and a number of medications used to treat multiple sclerosis including glatiramer acetate.

According to a European registry study, the mean age at onset of symptoms was 26.3 years old. As per the criteria laid out by ESID (European Society for Immunodeficiencies) and PAGID (Pan-American Group for Immunodeficiency), CVID is diagnosed if:

- the person presents with a marked decrease of serum IgG levels (<4.5 g/L) and a marked decrease below the lower limit of normal for age in at least one of the isotypes IgM or IgA;

- the person is four years of age or older;

- the person lacks antibody immune response to protein antigens or immunization.

Diagnosis is chiefly by exclusion, i.e. alternative causes of hypogammaglobulinemia, such as X-linked agammaglobulinemia, must be excluded before a diagnosis of CVID can be made.

Diagnosis is difficult because of the diversity of phenotypes seen in people with CVID. For example, serum immunoglobulin levels in people with CVID vary greatly. Generally, people can be grouped as follows: no immunoglobulin production, immunoglobulin (Ig) M production only, or both normal IgM and IgG production. Additionally, B cell numbers are also highly variable. 12% of people have no detectable B cells, 12% have reduced B cells, and 54% are within the normal range. In general, people with CVID display higher frequencies of naive B cells and lower frequencies of class-switched memory B cells. Frequencies of other B cell populations, such as IgD memory B cells, transitional B cells, and CD21 B cells, are also affected, and are associated with specific disease features. Although CVID is often thought of as a serum immunoglobulin and B cell-mediated disease, T cells can display abnormal behavior. Affected individuals typically present with low frequencies of CD4, a T-cell marker, and decreased circulation of regulatory T cells and iNKT cell. Notably, approximately 10% of people display CD4 T cell counts lower than 200 cells/mm; this particular phenotype of CVID has been named LOCID (Late Onset Combined Immunodeficiency), and has a poorer prognosis than classical CVID.

Treatment consists of antibiotics, elevation of the affected limb, and compression. For persons with elephantiasis nostras who are overweight or obese, weight loss is recommended. Oral retinoids have been used to treat the cutaneous manifestations of the disease.

Cutaneous lymphoid hyperplasia refers to a groups of benign cutaneous disorders characterized by collections of lymphocytes, macrophages, and dendritic cells in the skin. Conditions included in this groups are:

- Cutaneous lymphoid hyperplasia with nodular pattern, a condition of the skin characterized by a solitary or localized cluster of asymptomatic erythematous to violaceous papules or nodules

- Cutaneous lymphoid hyperplasia with bandlike and perivascular patterns, a condition of the skin characterized by skin lesions that clinically resemble mycosis fungoides