Erythema nodosum is diagnosed clinically. A biopsy can be taken and examined microscopically to confirm an uncertain diagnosis. Microscopic examination usually reveals a neutrophilic infiltrate surrounding capillaries that results in septal thickening, with fibrotic changes in the fat around blood vessels. A characteristic microscopic finding is radial granulomas, well-defined nodular aggregates of histiocytes surrounding a stellate cleft.

Additional evaluation should be performed to determine the underlying cause of erythema nodosum. This may include a full blood count, erythrocyte sedimentation rate (ESR), antistreptolysin-O (ASO) titer and throat culture, urinalysis, intradermal tuberculin test, and a chest x-ray. The ESR is typically high, the C-reactive protein elevated, and the blood showing an increase in white blood cells.

The ESR is initially very high, and falls as the nodules of erythema nodosum. The ASO titer is high in cases associated with a streptococcal throat infection. A chest X-ray should be performed to rule out pulmonary diseases, in particular sarcoidosis and Löfgren syndrome.

Diagnosis is clinical, based on observation. Biopsy is rarely required.

Alpha-1 antitrypsin deficiency panniculitis is a panniculitis associated with a deficiency of the α-antitrypsin enzyme.

Erythema nodosum is a form of panniculitis characterised by tender red nodules, 1–10 cm, associated with systemic symptoms including fever, malaise, and joint pain. Nodules may become bluish-purple, yellowing, and green, and subside over a period of 2–6 weeks without ulcerating or scarring. Erythema nodosum is associated with infections, including Hepatitis C, EBV and tuberculosis, Crohn's disease and sarcoidosis, pregnancy, medications including sulfonamides, and some cancers, including Non-Hodgkin lymphoma and pancreatic cancer.

Erythema nodosum is self-limiting and usually resolves itself within 3–6 weeks. A recurring form does exist, and in children it is attributed to repeated infections with streptococcus. Treatment should focus on the underlying cause. Symptoms can be treated with bedrest, leg elevation, compressive bandages, wet dressings, and nonsteroidal anti-inflammatory agents (NSAIDs). NSAIDs are usually more effective at the onset of EN versus with chronic disease.

Potassium iodide can be used for persistent lesions whose cause remains unknown. Corticosteroids and colchicine can be used in severe refractory cases. Thalidomide has been used successfully in the treatment of Erythema nodosum leprosum, and it was approved by the U.S. FDA for this use in July 1998.

The management of lipodermatosclerosis may include treating venous insufficiency with leg elevation and elastic compression stockings; in some difficult cases, the condition may be improved with the additional use of the fibrinolytic agent, stanozol. Fibrinolytic agents use an enzymatic action to help dissolve blood clots.

Stanozol is injected directly into the affected area, Venous Ablation has also been known to help circulation in patients.

Septal panniculitis is a condition of the subcutaneous fat affecting the layer of adipose tissue that lies between the dermis and underlying fascia, of which there are two forms: acute erythema nodosum and chronic erythema nodosum.

Neutrophilic lobular panniculitis is a cutaneous condition characterized by inflammation of the subcutaneous fat.

Weber–Christian disease, also known as relapsing febrile nodular nonsuppurative panniculitis, is a cutaneous condition characterized by recurrent subcutaneous nodules that heal with depression of the overlying skin.

It is type of panniculitis.

It is a rare disease seen in females 30–60 years of age. It is a recurring inflammation of fatty layers of tissue present beneath the skin. Clinical course is characterised by exacerbations and remissions. Lesions are bilaterally symmetrical and are usually seen in the lower legs.

Diagnosis of sarcoidosis is a matter of exclusion, as there is no specific test for the condition. To exclude sarcoidosis in a case presenting with pulmonary symptoms might involve a chest radiograph, CT scan of chest, PET scan, CT-guided biopsy, mediastinoscopy, open lung biopsy, bronchoscopy with biopsy, endobronchial ultrasound, and endoscopic ultrasound with fine-needle aspiration of mediastinal lymph nodes (EBUS FNA). Tissue from biopsy of lymph nodes is subjected to both flow cytometry to rule out cancer and special stains (acid fast bacilli stain and Gömöri methenamine silver stain) to rule out microorganisms and fungi.

Serum markers of sarcoidosis, include: serum amyloid A, soluble interleukin-2 receptor, lysozyme, angiotensin converting enzyme, and the glycoprotein KL-6. Angiotensin-converting enzyme blood levels are used in the monitoring of sarcoidosis. A bronchoalveolar lavage can show an elevated (of at least 3.5) CD4/CD8 T cell ratio, which is indicative (but not proof) of pulmonary sarcoidosis. In at least one study the induced sputum ratio of CD4/CD8 and level of TNF was correlated to those in the lavage fluid. A sarcoidosis-like lung disease called granulomatous–lymphocytic interstitial lung disease can be seen in patients with common variable immunodeficiency (CVID) and therefore serum antibody levels should be measured to exclude CVID.

Differential diagnosis includes metastatic disease, lymphoma, septic emboli, rheumatoid nodules, granulomatosis with polyangiitis, varicella infection, tuberculosis, and atypical infections, such as "Mycobacterium avium" complex, cytomegalovirus, and cryptococcus. Sarcoidosis is confused most commonly with neoplastic diseases, such as lymphoma, or with disorders characterized also by a mononuclear cell granulomatous inflammatory process, such as the mycobacterial and fungal disorders.

Chest radiograph changes are divided into four stages:

1. bihilar lymphadenopathy

2. bihilar lymphadenopathy and reticulonodular infiltrates

3. bilateral pulmonary infiltrates

4. fibrocystic sarcoidosis typically with upward hilar retraction, cystic and bullous changes

Although people with stage 1 radiographs tend to have the acute or subacute, reversible form of the disease, those with stages 2 and 3 often have the chronic, progressive disease; these patterns do not represent consecutive "stages" of sarcoidosis. Thus, except for epidemiologic purposes, this categorization is mostly of historic interest.

In sarcoidosis presenting in the Caucasian population, hilar adenopathy and erythema nodosum are the most common initial symptoms. In this population, a biopsy of the gastrocnemius muscle is a useful tool in correctly diagnosing the person. The presence of a noncaseating epithelioid granuloma in a gastrocnemius specimen is definitive evidence of sarcoidosis, as other tuberculoid and fungal diseases extremely rarely present histologically in this muscle.

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

Sarcoidosis may be divided into the following types:

- Annular sarcoidosis

- Erythrodermic sarcoidosis

- Ichthyosiform sarcoidosis

- Hypopigmented sarcoidosis

- Löfgren syndrome

- Lupus pernio

- Morpheaform sarcoidosis

- Mucosal sarcoidosis

- Neurosarcoidosis

- Papular sarcoid

- Scar sarcoid

- Subcutaneous sarcoidosis

- Systemic sarcoidosis

- Ulcerative sarcoidosis

Lupus erythematosus panniculitis (also known as "Lupus erythematosus profundus", "Lupus panniculitis", "Lupus profundus", and "Subcutaneous lupus erythematosus") presents with subcutaneous nodules that are commonly firm, sharply defined and nontender.

Treatment consists primarily of immunosuppressive drugs (e.g., hydroxychloroquine and corticosteroids). An interesting second line drug is methotrexate in its low-dose schedule. In 2011, the U.S. Food and Drug Administration (FDA) approved the first new drug for lupus in more than 50 years to be used in the US, belimumab. In addition to medicative therapy, due to the psychological and social impacts that Lupus may have on an individual, Cognitive Behavioural Therapy (CBT) has also been demonstrated to be effective in reducing stress, anxiety, and depression in lupus sufferers.

Erythema induratum is a panniculitis on the calves. It occurs mainly in women, but it is very rare now. Historically, when it has occurred, it has often been concomitant with cutaneous tuberculosis, and it was formerly thought to be always a reaction to the tuberculum bacillus. It is now considered a panniculitis that is not associated with just a single defined pathogen. The medical eponym Bazin disease was historically synonymous, but it applies only to the tuberculous form and is dated.

Atrophic connective tissue panniculitis is a rare condition, and often occurs on the upper or lower extremities.

It is named after Frederick Parkes Weber and Henry Asbury Christian.

Predisposing factors include abnormal amount of subcutaneous fat, thick ankles and abnormally poor arterial supply. Abnormal arterial supply causes low-grade ischemia of ankle region. The ankle skin becomes sensitive to temperature changes. When weather is cold, ankle is cold, blue and often tender. In hot weather, ankle becomes hot, edematous, swollen and painful. Chilblains may be present. On palpation, small superficial and painful nodules are felt. They break down to form small and multiple ulcers. Fresh crops of nodules appear in periphery of ulcer and ultimately break down. In nodular stage, pain is present; while it subsides in ulcerative stage.

A1AT deficiency remains undiagnosed in many patients. Patients are usually labeled as having COPD without an underlying cause. It is estimated that about 1% of all COPD patients actually have an A1AT deficiency. Thus, testing should be performed for all patients with COPD, asthma with irreversible airflow obstruction, unexplained liver disease, or necrotizing panniculitis. The initial test performed is serum A1AT level. A low level of A1AT confirms the diagnosis and further assessment with A1AT protein phenotyping and A1AT genotyping should be carried out subsequently. The Alpha-1 Foundation offers free, confidential testing.

As protein electrophoresis does not completely distinguish between A1AT and other minor proteins at the alpha-1 position (agarose gel), antitrypsin can be more directly and specifically measured using a nephelometric or immunoturbidimetric method. Thus, protein electrophoresis is useful for screening and identifying individuals likely to have a deficiency. A1AT is further analyzed by isoelectric focusing (IEF) in the pH range 4.5-5.5, where the protein migrates in a gel according to its isoelectric point or charge in a pH gradient.

Normal A1AT is termed M, as it migrates toward the center of such an IEF gel. Other variants are less functional and are termed A-L and N-Z, dependent on whether they run proximal or distal to the M band. The presence of deviant bands on IEF can signify the presence of alpha-1 antitrypsin deficiency. Since the number of identified mutations has exceeded the number of letters in the alphabet, subscripts have been added to most recent discoveries in this area, as in the Pittsburgh mutation described above. As every person has two copies of the A1AT gene, a heterozygote with two different copies of the gene may have two different bands showing on electrofocusing, although a heterozygote with one null mutant that abolishes expression of the gene will only show one band. In blood test results, the IEF results are notated as, e.g., PiMM, where Pi stands for protease inhibitor and "MM" is the banding pattern of that person.

Other detection methods include use of enzyme-linked-immuno-sorbent-assays in vitro and radial immunodiffusion.

Alpha 1-antitrypsin levels in the blood depend on the genotype. Some mutant forms fail to fold properly and are, thus, targeted for destruction in the proteasome, whereas others have a tendency to polymerize, thereafter being retained in the endoplasmic reticulum. The serum levels of some of the common genotypes are:

- PiMM: 100% (normal)

- PiMS: 80% of normal serum level of A1AT

- PiSS: 60% of normal serum level of A1AT

- PiMZ: 60% of normal serum level of A1AT

- PiSZ: 40% of normal serum level of A1AT

- PiZZ: 10-15% (severe alpha-1 antitrypsin deficiency)

Recombinant and inhaled forms of A1AT are being studied. Other experimental therapies are aimed at the prevention of polymer formation in the liver.

Poor prognostic factors include,

- Persistent synovitis

- Early erosive disease

- Extra-articular findings (including subcutaneous rheumatoid nodules)

- Positive serum RF findings

- Positive serum anti-CCP autoantibodies

- Carriership of HLA-DR4 "Shared Epitope" alleles

- Family history of RA

- Poor functional status

- Socioeconomic factors

- Elevated acute phase response (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP])

- Increased clinical severity.

Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment. The skin weighs an average of four kilograms, covers an area of two square meters, and is made of three distinct layers: the epidermis, dermis, and subcutaneous tissue. The two main types of human skin are: glabrous skin, the hairless skin on the palms and soles (also referred to as the "palmoplantar" surfaces), and hair-bearing skin. Within the latter type, the hairs occur in structures called pilosebaceous units, each with hair follicle, sebaceous gland, and associated arrector pili muscle. In the embryo, the epidermis, hair, and glands form from the ectoderm, which is chemically influenced by the underlying mesoderm that forms the dermis and subcutaneous tissues.

The epidermis is the most superficial layer of skin, a squamous epithelium with several strata: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Nourishment is provided to these layers by diffusion from the dermis, since the epidermis is without direct blood supply. The epidermis contains four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of these, keratinocytes are the major component, constituting roughly 95 percent of the epidermis. This stratified squamous epithelium is maintained by cell division within the stratum basale, in which differentiating cells slowly displace outwards through the stratum spinosum to the stratum corneum, where cells are continually shed from the surface. In normal skin, the rate of production equals the rate of loss; about two weeks are needed for a cell to migrate from the basal cell layer to the top of the granular cell layer, and an additional two weeks to cross the stratum corneum.

The dermis is the layer of skin between the epidermis and subcutaneous tissue, and comprises two sections, the papillary dermis and the reticular dermis. The superficial papillary dermis with the overlying rete ridges of the epidermis, between which the two layers interact through the basement membrane zone. Structural components of the dermis are collagen, elastic fibers, and ground substance. Within these components are the pilosebaceous units, arrector pili muscles, and the eccrine and apocrine glands. The dermis contains two vascular networks that run parallel to the skin surface—one superficial and one deep plexus—which are connected by vertical communicating vessels. The function of blood vessels within the dermis is fourfold: to supply nutrition, to regulate temperature, to modulate inflammation, and to participate in wound healing.

The subcutaneous tissue is a layer of fat between the dermis and underlying fascia. This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source.

Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying etiologies and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), etiology (skin conditions resulting from physical factors), and so on. Clinically, the diagnosis of any particular skin condition is made by gathering pertinent information regarding the presenting skin lesion(s), including the location (such as arms, head, legs), symptoms (pruritus, pain), duration (acute or chronic), arrangement (solitary, generalized, annular, linear), morphology (macules, papules, vesicles), and color (red, blue, brown, black, white, yellow). Diagnosis of many conditions often also requires a skin biopsy which yields histologic information that can be correlated with the clinical presentation and any laboratory data.

The course of the disease varies greatly. Some people have mild short-term symptoms, but in most the disease is progressive for life. Around 20%–30% will have subcutaneous nodules (known as rheumatoid nodules); this is associated with a poor prognosis.

Urticaria is a vascular reaction of the skin characterized by the appearance of wheals, which are firm, elevated swelling of the skin. Angioedema, which can occur alone or with

urticaria, is characterized by a well-defined, edematous swelling that involves subcutaneous tissues, abdominal organs, or upper airway.

- Acquired C1 esterase inhibitor deficiency

- Acute urticaria

- Adrenergic urticaria

- Anaphylaxis

- Aquagenic urticaria

- Cholinergic urticaria

- Chronic urticaria (ordinary urticaria)

- Cold urticaria

- Dermatographism (dermographism)

- Episodic angioedema with eosinophilia (Gleich's syndrome)

- Exercise urticaria (exercise-induced urticaria)

- Galvanic urticaria

- Heat urticaria

- Hereditary angioedema (Quincke's edema)

- Localized heat contact urticaria

- Mast cell-independent urticaria

- Physical urticaria

- Primary cold contact urticaria

- Pressure urticaria (delayed pressure urticaria)

- Reflex cold urticaria

- Schnitzler syndrome

- Secondary cold contact urticaria

- Solar urticaria

- Systemic capillary leak syndrome

- Urticarial allergic eruption

- Urticaria-like follicular mucinosis

- Vibratory angioedema

Subcutaneous fat necrosis of the newborn (SCFN or SFN) is a rare form of lobular panniculitis occurring in newborns that is usually self-remitting and non-recurring. Proposed causes include perinatal stress, local trauma, hypoxia and hypothermia, though the exact cause is unknown. It has been suggested that the brown fat seen in newborns is more sensitive to hypoxic injury than fat seen in adults, and that such hypoxia, usually in the context of a complicated birth, leads to the fat necrosis. Complications can include hypercalcemia, hyperlipidemia and thrombocytopenia, and can present months after the onset of SCFN symptoms.