Panniculitis: Symptoms, Types, Causes and Treatment

Panniculitis is a diverse group of inflammatory disorders affecting the subcutaneous fat layer. While relatively uncommon, its various forms can be confusing due to overlapping symptoms and complex underlying causes. Understanding the distinguishing features, triggers, and treatment options is crucial for both patients and clinicians. This article provides an in-depth, evidence-based overview of panniculitis, covering its symptoms, main types, causes, and the latest treatment strategies.

Symptoms of Panniculitis

Panniculitis often presents with symptoms that can be alarming and uncomfortable. Recognizing these symptoms early can help guide appropriate diagnostic steps and inform further management.

Symptom	Description	Frequency/Pattern	Source(s)
Nodules	Painful, red, or purple lumps under skin	Common, often on lower limbs	1 4 6
Fever	Elevated body temperature	Sometimes present	1 2 6
Arthralgia	Joint pain	Occasional; may accompany nodules	1 2 6
Malaise	General feeling of illness	Non-specific, often present	1 6
Ulceration	Skin breakdown, sometimes with discharge	In severe or lobular forms	2 3
Systemic Signs	Lymphadenopathy, myasthenic syndrome	Less common, in specific subtypes	2 11

Table 1: Key Symptoms

Overview of Common Symptoms

The hallmark of panniculitis is the sudden appearance of tender, erythematous (red) or violaceous (purple) subcutaneous nodules or plaques. These lesions are most frequently found on the lower extremities, particularly the anterior shins, but can also appear on the arms, trunk, and less commonly, the face 1 4 6.

Associated Systemic Symptoms

• Fever and Malaise: A significant number of patients experience systemic symptoms such as fever and a general sense of being unwell. These symptoms may precede or accompany the skin lesions 1 2 6.
• Arthralgia: Joint pain, particularly in the knees and ankles, is often reported, especially in erythema nodosum 1 6.
• Ulceration and Discharge: While many cases of panniculitis are non-ulcerative, more severe or chronic forms, such as lobular panniculitis or panniculitis associated with autoimmune diseases, may result in skin ulceration, sometimes with leakage of oily or serous fluid 2 3.
• Other Systemic Features: In rare or severe cases, additional symptoms can include lymph node enlargement, myasthenic syndrome (muscle weakness), and signs indicative of multi-system involvement, particularly in autoimmune-related panniculitis or lymphomas 2 11.

Symptom Evolution

Symptoms may develop suddenly or gradually. In some types, such as erythema nodosum, there is often a prodrome of fever, malaise, or upper respiratory symptoms lasting one to three weeks before nodules appear 6. The nodules themselves typically resolve over several weeks, sometimes leaving behind temporary discoloration or, rarely, scarring and atrophy 1 6.

Types of Panniculitis

Because panniculitis is not a single disease but rather a pattern of inflammation, it encompasses several distinct types, each with unique clinical and pathological features.

Type	Main Features	Typical Location/Population	Source(s)
Erythema nodosum	Septal, non-ulcerative nodules	Shins, young women	1 4 5 6 7
Erythema induratum	Lobular, often ulcerative, vasculitic	Calves, middle-aged women	3 5 7 8
Infectious panniculitis	Varies, may be necrotic	Any subcutaneous tissue	3 7 8 9
Connective tissue panniculitis	Associated with SLE, DM, scleroderma	Arms, trunk, variable	3 7 8 14
Pancreatic panniculitis	Fat necrosis, lobular	Legs, associated with pancreatitis	3 7 8
Alpha-1-antitrypsin deficiency panniculitis	Lobular, often ulcerative	Lower limbs, any age	3 7 8
Subcutaneous T-cell lymphoma	Neoplastic, mimics lobular panniculitis	Trunk, limbs, adults	3 7 11
Mesenteric panniculitis	Chronic, abdominal fat involved	Mesentery, adults	10

Table 2: Main Types of Panniculitis

Classification by Histopathology

Panniculitis is classified based on which part of the subcutaneous fat is primarily affected:

• Septal Panniculitis: Inflammation centers on the fibrous septa between fat lobules. Erythema nodosum is the classic example. It is characterized by non-ulcerative, tender nodules and typically lacks vasculitis 4 6 7 8.
• Lobular Panniculitis: The inflammation is within the fat lobules themselves. This group includes conditions such as erythema induratum (which often involves vasculitis), autoimmune-associated panniculitis, infectious forms, and cases related to metabolic or genetic factors 3 7 8.

Major Clinical Subtypes

• Erythema Nodosum: The most common form, especially in women and young adults. Presents with symmetrical, painful nodules on the shins. It is generally self-limited and non-ulcerative 1 4 5 6.
• Erythema Induratum (Nodular Vasculitis): Classically associated with tuberculosis or other underlying diseases, presenting as tender, sometimes ulcerated nodules on the calves. Histologically, it is a lobular panniculitis with vasculitis 3 5 7.
• Infectious Panniculitis: Can be caused by bacteria, fungi, or parasites. Lesions may become necrotic or ulcerative, particularly if not treated promptly 9.
• Connective Tissue Disease-Related Panniculitis: Seen in conditions such as lupus erythematosus, dermatomyositis, and scleroderma/morphea. May result in chronic inflammation, scarring, and calcification 3 7 8 14.
• Pancreatic and Enzyme-Related Panniculitis: Occurs in the context of pancreatitis or pancreatic cancer, leading to fat necrosis and characteristic subcutaneous nodules 3 7 8.
• Alpha-1-Antitrypsin Deficiency Panniculitis: A rare but distinctive form, often with ulcerative lesions, seen in patients with inherited alpha-1-antitrypsin deficiency 3 7 8.
• Subcutaneous Panniculitis-like T-cell Lymphoma: A rare malignancy that can mimic inflammatory panniculitis but requires specific treatment 3 7 11.
• Mesenteric Panniculitis: Uncommonly affects the abdominal mesentery, causing abdominal pain, mass effect, and sometimes bowel symptoms 10.

Causes of Panniculitis

Panniculitis may be triggered by a wide array of factors, ranging from infections and autoimmune disorders to drugs, trauma, and genetic conditions.

Cause Category	Specific Triggers/Associations	Notable Features	Source(s)
Idiopathic	No identifiable cause	Up to 55% of EN cases	6
Infection	Bacteria, fungi, mycobacteria, viruses	May lead to necrotic lesions	3 7 9
Autoimmune/Inflammatory	Lupus, dermatomyositis, scleroderma	Often chronic, with systemic signs	2 3 8 14
Drugs	Sulfonamides, oral contraceptives, biologics	Drug-induced inflammation	6 8
Trauma/Procedures	Surgery, injections, liposuction	Localized lesions, sometimes with oil discharge	2 3 7
Metabolic/Enzyme Defects	Pancreatitis, alpha-1-antitrypsin deficiency	Fat necrosis, ulceration	3 7 8
Malignancy	Paraneoplastic (cancer-associated), lymphomas	May mimic or complicate other types	1 3 7 11
Genetic	Alpha-1-antitrypsin deficiency	Familial, recurrent or severe	3 7 8

Table 3: Main Causes of Panniculitis

Idiopathic and Multifactorial Triggers

Many cases, particularly of erythema nodosum, remain idiopathic, meaning no underlying cause is identified even after thorough investigation. This accounts for up to 55% of EN cases 6.

Infectious Triggers

• Bacterial: Streptococcal infections are a classic cause of erythema nodosum, but other bacteria, fungi, and even mycobacteria (especially in erythema induratum) can trigger panniculitis 3 7 9.
• Viral and Parasitic: Although rare, these can also be implicated, particularly in immunocompromised patients 9.

Autoimmune and Inflammatory Diseases

Panniculitis is often a manifestation of underlying autoimmune disorders such as:

• Systemic lupus erythematosus (lupus panniculitis)
• Dermatomyositis
• Scleroderma/morphea
• Mixed connective tissue diseases
• ASIA (autoimmune/inflammatory syndrome induced by adjuvants) 2 3 8 14

These cases may present with more chronic, relapsing symptoms and require systemic therapy.

Drug-Induced and Procedural Causes

Certain medications (sulfonamides, oral contraceptives, biologics) and procedures (injections, surgery, cosmetic procedures like liposuction or gluteoplasty) can incite panniculitis, particularly in genetically susceptible individuals 2 6 8.

Metabolic and Genetic Disorders

• Pancreatic Disease: Pancreatitis or pancreatic cancer can cause enzymatic fat necrosis leading to panniculitis 3 7 8.
• Alpha-1-Antitrypsin Deficiency: This hereditary condition can present as recurrent, ulcerative panniculitis 3 7 8.

Malignancy-Associated and Neoplastic Forms

Some cases of panniculitis are paraneoplastic (triggered by underlying cancer), or represent actual lymphomas mimicking panniculitis (subcutaneous panniculitis-like T-cell lymphoma) 1 3 7 11.

Trauma and Factitial Causes

Physical injury, injections, or even chronic venous insufficiency can induce localized panniculitis 3 7.

Treatment of Panniculitis

Effective treatment of panniculitis hinges on identifying and addressing the underlying cause, while also providing symptomatic relief and preventing complications.

Treatment Type	Example/Approach	Indications	Source(s)
Symptomatic	NSAIDs, rest, compression	Most erythema nodosum, mild cases	5 6
Address underlying trigger	Antibiotics, anti-TB drugs	Infectious, tuberculous, or drug-induced	5 9
Systemic corticosteroids	Prednisone, dexamethasone	Severe, autoimmune, or refractory cases	12 13 14
Immunosuppressive agents	Methotrexate, cyclosporine, azathioprine	Autoimmune, SPTCL, resistant cases	11 12 14
Antimalarials	Hydroxychloroquine	Lupus panniculitis	14
Biologics/targeted therapy	Anakinra (IL-1 blocker)	Neutrophilic panniculitis, difficult cases	13
Potassium iodide, colchicine	Adjuncts for EN, EI	Recurrent or persistent nodular panniculitis	5
Surgical excision	Removal of isolated nodules	Sterile panniculitis, diagnostic uncertainty	12 10
Supportive care	Compression, wound care	All types, especially with ulceration	5 12

Table 4: Main Treatments for Panniculitis

General Principles

Treatment strategies are guided by the underlying cause, severity, and individual patient factors. In many cases, especially with erythema nodosum, the condition is self-limited and only symptomatic management is needed 5 6.

Symptomatic and Supportive Management

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Help relieve pain and inflammation associated with nodules 5 6.
• Rest and Compression: Especially useful for nodular panniculitis of the lower limbs 5.
• Wound Care: For ulcerative or necrotic lesions, appropriate wound management is essential 5 12.

Treating Underlying Causes

• Infectious Triggers: Antibiotics for bacterial causes, antifungals for fungal cases, and anti-tuberculous therapy for tuberculosis-associated erythema induratum 5 9.
• Drug Withdrawal: Stopping the offending drug can lead to resolution 6.
• Cancer Treatment: For paraneoplastic panniculitis, managing the underlying malignancy is key 1.

Systemic Therapy

• Corticosteroids: Oral or topical steroids are used for severe, rapidly progressing, or autoimmune-related panniculitis 12 14.
• Immunosuppressants: Methotrexate, azathioprine, cyclosporine, or mycophenolate mofetil may be indicated for autoimmune forms or subcutaneous panniculitis-like T-cell lymphoma, often in combination with steroids 11 12 14.
• Antimalarials: Hydroxychloroquine is first-line for lupus panniculitis 14.
• Biologic Agents: IL-1 inhibitors like anakinra have shown promise in difficult-to-treat neutrophilic panniculitis 13.

Adjunctive and Specialized Therapies

• Potassium Iodide, Colchicine: Sometimes used as adjuncts in erythema nodosum or erythema induratum 5.
• Surgical Excision: Reserved for isolated, persistent nodules or when malignancy cannot be excluded 12 10.
• Other Modalities: In rare cases, radiotherapy or other specialized treatments may be considered, particularly in neoplastic forms 11.

Treatment of Specific Subtypes

• Erythema Nodosum: Symptomatic care plus treatment of any identified underlying cause. Most cases resolve spontaneously 5 6.
• Erythema Induratum: Anti-tuberculous drugs if TB is present, otherwise therapy similar to EN 5.
• Connective Tissue Disease-Related Panniculitis: Systemic corticosteroids and immunosuppressives; antimalarials for lupus 14.
• SPTCL: Immunosuppressive therapy is now considered preferable to chemotherapy 11.
• Mesenteric Panniculitis: Empirical drug therapy; surgery is rarely needed 10.

Conclusion

Panniculitis encompasses a complex spectrum of disorders involving inflammation of subcutaneous fat. Accurate diagnosis relies on recognizing clinical features, understanding the diverse causes, and integrating histopathology. While many cases are self-limited, others require targeted therapy and multidisciplinary management.

Key Takeaways:

• Panniculitis presents mainly with painful subcutaneous nodules, often accompanied by systemic symptoms.
• Major types include erythema nodosum (septal), erythema induratum (lobular/vasculitic), infectious, autoimmune, metabolic, and neoplastic forms.
• Causes range from infections and autoimmune diseases to drugs, trauma, metabolic disorders, and malignancy.
• Treatment is individualized: many cases resolve with supportive care, but others require immunosuppressive, antimicrobial, or targeted therapies.
• Multidisciplinary approach is often essential, especially in complex or refractory cases.

Understanding panniculitis and its many faces is crucial for effective diagnosis and management, ultimately improving patient outcomes.