Eruptive Xanthomas

Fig. 26.21 - Eruptive xanthomas (Andrews' Diseases of the Skin)

Definition

Clinical Features

Pathogenesis

Causes / Associated Conditions

Primary (Genetic) Disorders

Secondary (Acquired) Causes

• Poorly controlled type 2 diabetes mellitus (most common)
• Chronic renal failure
• Hypothyroidism
• Drug-induced: estrogens, corticosteroids, systemic retinoids
• Alcohol excess
• Metabolic syndrome / obesity

Key clinical pearl: Eruptive xanthomas are seen in ~8.5% of patients presenting with severe hypertriglyceridemia (TG >1,772 mg/dL). They should always prompt urgent lipid workup.

Associated Systemic Findings

• Lipemia retinalis (retinal vessels appear creamy-white)
• Hepatosplenomegaly (triglyceride deposition in liver/spleen)
• Acute pancreatitis (5% risk at TG >1,000 mg/dL; 10-20% at TG >2,000 mg/dL)
• Lactescent (milky) serum on centrifugation

Differential Diagnosis

• Granuloma annulare (generalized)
• Molluscum contagiosum
• Subepidermal calcified nodules
• Xanthoma disseminatum (normolipemic)
• Sarcoidosis
• Eruptive syringomas

Diagnosis

1. Fasting lipid panel - triglycerides typically >1,000 mg/dL
2. Skin biopsy - foamy macrophages (foam cells) in superficial dermis with lymphocytic infiltrate
3. Serum appearance - lactescent or milky
4. Workup for secondary causes: fasting glucose/HbA1c, TSH, renal function

Treatment

Lipid-Lowering Therapy

• Fibrates (e.g., fenofibrate) - first-line for severe hypertriglyceridemia
• Omega-3 fatty acids (high-dose) - reduce VLDL synthesis
• Statins - useful if combined hyperlipidemia
• Nicotinic acid - reduces VLDL; limited by side effects

Dietary / Lifestyle

• Strict low-fat diet (critical in chylomicronemia syndrome)
• Alcohol cessation
• Tight glycemic control in diabetics

Specific/Advanced

• Alipogene tiparvovec (gene therapy) for monogenic LPL deficiency
• Volanesorsen (antisense oligonucleotide targeting ApoC-III) for familial chylomicronemia syndrome - a newer option

Skin lesions

Prognosis

• Lesions resolve within weeks of initiating effective lipid-lowering treatment
• Main risks are from the underlying disorder: pancreatitis and cardiovascular disease
• Recurrence occurs if the metabolic trigger (e.g., poor diabetes control) returns

Mechanism: Diabetes → Hypertriglyceridemia → Eruptive Xanthomas

1. Reduced lipoprotein lipase (LPL) activity - LPL normally breaks down triglycerides in chylomicrons and VLDL. Insulin is required to activate LPL. Without adequate insulin action, LPL activity falls sharply.
2. Increased VLDL production - The liver produces excess VLDL due to elevated free fatty acid flux (from uninhibited lipolysis in adipose tissue).
3. Result: Severe hypertriglyceridemia - Triglycerides accumulate in the bloodstream (often >1,000 mg/dL).
4. Dermal macrophage overload - Circulating chylomicrons and VLDL particles are phagocytosed by dermal macrophages, forming foam cells → visible as eruptive xanthoma papules.

Key Points

• Eruptive xanthomas can be the first presenting sign of previously undiagnosed diabetes mellitus
• They are seen most often in type 2 DM, but can occur in type 1 DM with poor control
• The hypertriglyceridemia in DM is reversible - once glycemic control is restored, LPL activity recovers, triglycerides fall, and lesions resolve within weeks
• Poorly controlled DM is an example of a secondary (acquired) cause of hypertriglyceridemia, unmasking a polygenic predisposition in susceptible individuals

Clinical Implication

• Fasting glucose / HbA1c checked immediately
• A full fasting lipid panel
• Assessment for other secondary causes (hypothyroidism, renal failure, drugs)

Acute Pancreatitis - Treatment

Diagnosis First (Quick Review)

1. Abdominal pain characteristic of acute pancreatitis (epigastric, radiating to back)
2. Serum lipase (preferred) or amylase >3x upper limit of normal
3. Characteristic findings on CT/MRI

Note: Lipase is more sensitive and specific than amylase. The degree of elevation does not correlate with severity.

Severity Classification

Treatment

1. Fluid Resuscitation (Cornerstone)

• Aggressive IV hydration is the most important early intervention
• Lactated Ringer's (LR) is the preferred fluid - reduces SIRS and progression compared to normal saline
• Rate: 250-500 mL/hour in the first 12-24 hours (or 1.5-2x maintenance)
• Goal: urine output >0.5 mL/kg/hr, HR <100 bpm, MAP >65 mmHg
• Reassess frequently - over-resuscitation causes abdominal compartment syndrome

2. Analgesia

• Opioids (e.g., IV morphine or hydromorphone) - effective and safe; the old concern that morphine worsens pancreatitis via sphincter of Oddi spasm is not clinically significant
• NSAIDs (e.g., ketorolac) - useful adjunct
• Adequate pain control improves patient comfort and reduces stress response

3. Nutrition

• Early oral/enteral feeding (within 24-48 hours) is now strongly recommended - even in severe cases
• Nil per os (NPO) is no longer standard for mild-moderate disease
• Start with a low-fat, soft diet as soon as tolerated; not necessary to wait for pain/enzyme resolution
• In severe cases: nasojejunal (NJ) tube feeding is preferred over parenteral nutrition
• Total parenteral nutrition (TPN) only if enteral route is not tolerated or contraindicated
• Enteral nutrition preserves gut barrier, reduces bacterial translocation, lowers infectious complications

4. Antibiotics

• NOT indicated prophylactically in acute pancreatitis, even in necrotizing disease
• Use antibiotics only if there is confirmed infected necrosis or another concurrent infection (cholangitis, bacteremia)
• Empiric broad-spectrum antibiotics (e.g., imipenem, meropenem) if infected pancreatic necrosis is suspected (fever + deterioration + gas in necrosis on CT)

5. Imaging

• CT with IV contrast is NOT routine at admission
• Indicated if: diagnostic uncertainty, failure to improve after 48-72 hours, or suspected complication
• Best performed ≥72 hours after onset - early CT underestimates necrosis
• CT Severity Index (CTSI) helps grade severity and predict outcomes

6. Cause-Specific Treatment

7. Management of Complications

8. What NOT to Do

• Do not give prophylactic antibiotics routinely
• Do not keep the patient NPO unnecessarily
• Do not do early CT routinely
• Do not delay cholecystectomy in gallstone pancreatitis if mild

Updated Guidelines (2025)

Image Analysis

Condyloma Acuminata (Genital Warts)

Etiology

• Caused by Human Papillomavirus (HPV), most commonly types 6 and 11 (low-risk, rarely associated with malignancy)
• HPV types 16 and 18 are high-risk and associated with dysplasia and squamous cell carcinoma
• Transmitted via sexual contact (vaginal, anal, oral) or skin-to-skin contact; rarely by perinatal transmission

Sites of Occurrence

• Perianal skin and anal canal
• Genital region (penis, vulva, vagina, cervix)
• Inguinal folds, oral mucosa

Clinical Features

• Lesions range from small, flesh-colored papules to large cauliflower-like exophytic masses
• May be asymptomatic, or cause pruritus, burning, bleeding, discharge, or pain
• Application of 5% acetic acid turns lesions white (acetowhitening) - aids identification

Diagnosis

• Clinical diagnosis in most cases
• Biopsy with histopathology to confirm - especially important in immunocompromised patients to rule out high-grade squamous intraepithelial neoplasia (HSIL) or malignancy
• Colposcopy / anoscopy / sigmoidoscopy to assess extent

Differential Diagnosis

Treatment

Patient-Applied (Self-administered)

Provider-Applied (Office/Clinic)

Operating Room (Severe/Extensive Disease)

• Surgical excision under anesthesia
• CO2 laser under anesthesia
• Clearance rate: 60-90% after surgery; recurrence rate: 20-30% within first few months

Special Situations

• Pregnancy: Podophyllin and podophyllotoxin are contraindicated; imiquimod use requires caution. TCA and cryotherapy preferred.
• Immunosuppressed (HIV, transplant): Higher recurrence rates; biopsy all lesions to exclude HSIL; may need more aggressive treatment
• Pediatric condyloma: Perinatal transmission possible; CO2 laser and imiquimod used; consider sexual abuse evaluation

No Single Superior Treatment

Prevention

• HPV vaccination (Gardasil 9) - protects against HPV types 6, 11, 16, 18 and five additional high-risk types
• Recommended for ages 9-26 years (can be given up to age 45)
• Condom use reduces but does not eliminate transmission (skin beyond condom coverage can still transmit)

Note on Image 3: The herpetiform clustered vesicles with erythematous base in that image raise the possibility of co-existing Herpes Simplex Virus (HSV) infection - HSV and HPV can co-exist. Viral swab / PCR of the vesicular lesions would help differentiate. HSV treatment requires acyclovir/valacyclovir, not the treatments listed above.

Treatment of Condyloma Acuminata in Male Patients

Site-Specific Considerations in Males

Treatment Options

A. Patient-Applied (Self-administered at Home)

1. Podophyllotoxin (Podofilox) 0.5% solution or gel

• How: Apply to warts twice daily for 3 consecutive days, then 4 days rest - repeat up to 4 cycles
• Best for: External genital and perianal warts on keratinized skin
• Not for: Urethral meatus, intra-anal, or mucosal surfaces; avoid >10 cm² area
• Side effects: Local irritation, erosion, burning
• Note: Solution (0.5%) is preferred over 0.15% cream where easily applied (BASHH 2024 guideline)

2. Imiquimod 5% cream

• How: Apply 3 times per week at bedtime, wash off after 6-10 hours - up to 16 weeks
• Mechanism: Immune response modifier (Toll-like receptor 7 agonist) - stimulates local interferon and cytokine response
• Best for: Keratinized skin; external penile, perianal lesions; also useful as adjunct after ablation to reduce recurrence
• Side effects: Local erythema, erosion, itching, flu-like symptoms
• Lower recurrence rates than ablative methods alone

3. Sinecatechins 15% ointment (green tea polyphenols)

• Apply 3 times daily for up to 16 weeks
• Alternative for external genital warts

B. Provider-Applied (Clinic/Office)

1. Cryotherapy (Liquid Nitrogen)

• Freeze-thaw technique applied directly to the lesion; repeat every 1-2 weeks
• Effective for penile shaft, scrotal, perianal lesions
• For urethral meatus warts: cryotherapy is an option if the wart base is clearly visible on meatal eversion (examine with otoscope/meatoscope)
• Combination with podophyllotoxin has improved outcomes in men
• No systemic effects; fume extraction needed for anal lesions

2. Trichloroacetic Acid (TCA) 80-90%

• Applied precisely with a cotton-tipped swab by the clinician
• Safe on mucosal surfaces (glans, urethral meatus, intra-anal)
• Useful for recurrent lesions after initial clearance
• Repeat weekly as needed

3. Electrocautery / Fulguration

• Highly effective for perianal and multiple lesions
• Needle-tip cautery allows precise targeting with minimal surrounding tissue damage
• For large perianal disease: electrocautery fulguration is the mainstay - lesions turned white, then eschar formed and curetted
• Risk of smoke plume containing viable virus - appropriate PPE required

4. Surgical Excision (Shave/Tangential excision)

• For large, bulky, or resistant lesions
• Allows tissue for histopathology (important in immunosuppressed patients)
• Suture closure is contraindicated for penile lesions (distorts anatomy, impairs healing)

5. CO2 Laser Ablation

• Most effective for extensive, confluent, or multi-site disease
• ~70% response rate for perigenital lesions
• Requires appropriate ventilation/fume extraction (viable HPV in laser plume)

6. Photodynamic Therapy (PDT - 5-aminolevulinic acid)

• Emerging evidence specifically for urethral condyloma in male patients
• Effective and well-tolerated for intraurethral warts

C. Urethral Meatus / Intraurethral Warts (Male-Specific)

• Examine the urethral orifice with a good light source and meatoscope/otoscope
• Cryotherapy - if wart base is clearly visible
• PDT (photodynamic therapy) - increasing evidence for effectiveness
• CO2 laser or electrosurgery - preferred for deeper intraurethral involvement
• Podophyllotoxin and TCA can be used at the visible meatal surface only
• Urology referral recommended for intraurethral disease

D. Perianal / Intra-anal Warts (Management Strategy)

• Operating room under sedation - allows thorough examination, acetic acid counterstaining, representative biopsy for histology, then electrocautery fulguration
• Islands of normal skin can be preserved even in confluent disease
• For circumferential disease: stage treatment (treat half at a time, allow healing, return in 3-4 weeks)

• Office-applied TCA for small recurrent lesions
• Imiquimod or podofilox self-applied at home
• Best approach: combination of ablative therapy + imiquimod adjunct - reduces recurrence rate significantly

Summary Table

Important Points for Male Patients

1. No single treatment is superior - choice depends on site, burden, and recurrence history
2. Recurrence is common (20-30%) within the first few months - counsel the patient
3. Biopsy all lesions in immunosuppressed males (HIV, transplant) - high co-incidence of HSIL
4. Test for other STIs: syphilis (RPR), HIV, gonorrhea, chlamydia
5. Partner notification and treatment - sexual partners should be examined
6. HPV vaccination (Gardasil 9): Recommended up to age 45 - even in those already infected, reduces reinfection with other HPV types
7. Spontaneous resolution occurs in up to 75% within 2 years without treatment, but treatment is recommended due to risk of spread, transmission to partners, and rare malignant transformation