A previously healthy 46-year-old woman comes to her physician because of an itchy rash on her legs. She denies any recent trauma, insect bites, or travel. Her vital signs are within normal limits. Examination of the oral cavity shows white lace-like lines on the buccal mucosa. A photograph of the rash is shown. A biopsy specimen of the skin lesion is most likely to show which of the following?

Lymphocytes at the dermoepidermal junction

Inflammation of subcutaneous adipose tissue

Proliferation of vascular endothelium

Decreased thickness of the stratum granulosum

Deposition of antibodies around epidermal cells

A 29-year-old man presents to the clinic complaining of fatigue and loss of sensation in his lower legs. The patient notes no history of trauma or chronic disease but states that he spends a lot of time outside and often encounters wild animals. On examination, the patient has multiple dark lesions over the skin of his face and back, as well as a decreased sensation of fine touch and vibration bilaterally in the lower extremities. What is the morphology of the etiologic agent causing this patient’s symptoms?

An acid-fast, intracellular bacillus

Reactivation of latent viral infection

Maltose-fermenting gram-negative diplococci

A spirochete transmitted via tick

Gram-positive, branching anaerobe

A 50-year-old female presents to her physician with vesicles and tense blisters across her chest, arms, and the back of her shoulders. Physical examination reveals that blistering is not present in her oral mucosa, and the epidermis does not separate upon light stroking of the skin. The patient most likely suffers from a hypersensitivity reaction located:

Linearly along the epidermal basement membrane

In nuclei within epidermal cells

In net-like patterns around epidermal cells

In granular deposits at the tips of dermal papillae

A 54-year-old man comes to the physician because of a cough with blood-tinged sputum for 1 week. He also reports fever and a 5-kg (11 lb) weight loss during the past 2 months. Over the past year, he has had 4 episodes of sinusitis. Physical examination shows palpable nonblanching skin lesions over the hands and feet. Examination of the nasal cavity shows ulceration of the nasopharyngeal mucosa and a depressed nasal bridge. Oral examination shows a painful erythematous gingival enlargement that bleeds easily on contact. Which of the following is the most likely cause of the patient's symptoms?

Metalloprotease enzyme deficiency

Malignant myeloid cell proliferation

A 37-year-old woman presents to the occupational health clinic for a new employee health screening. She has limited medical records prior to her immigration to the United States several years ago. She denies any current illness or significant medical history. Purified protein derivative (PPD) is injected on the inside of her left forearm for tuberculosis (TB) screening. Approximately 36 hours later, the patient comes back to the occupational health clinic and has an indurated lesion with bordering erythema measuring 15 mm in diameter at the site of PPD injection. Of the following options, which is the mechanism of her reaction?

Type IV–cell-mediated (delayed) hypersensitivity reaction

Type III and IV–mixed immune complex and cell-mediated hypersensitivity reactions

Type III–immune complex-mediated hypersensitivity reaction

Type I–anaphylactic hypersensitivity reaction

Type II–cytotoxic hypersensitivity reaction

Panniculitis for USMLE Step 3: High-Yield Pathology Lessons

Panniculitis - Fat Under Fire

Definition: Inflammation of subcutaneous fat (panniculus adiposus), presenting as deep, tender, erythematous nodules, typically on the lower extremities.
Diagnosis: Requires a deep incisional or excisional biopsy for accurate histologic classification, which is crucial for determining the underlying cause and appropriate management.

Erythema Nodosum on Shins

⭐ Erythema nodosum (septal, no vasculitis) is the most common form. It represents a delayed hypersensitivity reaction to various stimuli like infections (Strep), sarcoidosis, IBD, and drugs (OCPs).

Erythema Nodosum - Shins on Fire

Pathophysiology: A delayed-type (Type IV) hypersensitivity reaction affecting the septa of subcutaneous fat.
Clinical: Presents as tender, erythematous, non-ulcerated nodules, classically on the anterior shins. Fever and arthralgias are common.
Histology: Septal panniculitis without primary vasculitis. Early lesions show edema, hemorrhage, and neutrophils; later lesions have lymphocytes, histiocytes, and giant cells, including characteristic Miescher's radial granulomas.
Associations:
- 📌 Mnemonic: ENjoys SODA
  - Sarcoidosis / Streptococcal infection
  - OCPs
  - Drugs (sulfonamides)
  - Autoimmune (e.g., IBD)

⭐ In children, streptococcal infection is the most common trigger, whereas in adults, it's often idiopathic or linked to sarcoidosis.

Differential Diagnosis of Lower Extremity Skin Lesions

Erythema Induratum - Calf Ulcer Attack

Pathophysiology: A mostly lobular panniculitis involving a T-cell mediated hypersensitivity reaction, often with vasculitis.
Clinical Presentation:
- Tender, erythematous nodules primarily on the posterior calves.
- Characteristically ulcerate, drain, and heal with scarring, distinguishing it from erythema nodosum.
Histology:
- Lobular or mixed septal-lobular panniculitis.
- Necrotizing vasculitis of small to medium-sized vessels within the fat lobules.
Associations:
- Strongly associated with Mycobacterium tuberculosis (scrofuloderma).
- Also linked to other infections like Nocardia and hepatitis C.

⭐ When linked to tuberculosis, it's termed Bazin's disease. A positive PPD test or IGRA is a key diagnostic clue.

Erythema induratum: clinical presentation and histology

Other Types - The Unusual Suspects

Alpha-1-Antitrypsin Deficiency: A lobular panniculitis with liquefactive necrosis, leading to oily discharge and ulceration. Diagnosis requires checking A1AT levels.
Factitial Panniculitis: Self-induced by injecting foreign substances (e.g., oils, milk). Presents with bizarre, angular lesions. Histology reveals foreign material.
Pancreatic Panniculitis: Lobular type associated with pancreatitis or pancreatic cancer.

⭐ Histology classically shows "ghost cells"-anucleated adipocytes with calcified walls from saponification.

Pancreatic Panniculitis Histology

High‑Yield Points - ⚡ Biggest Takeaways

Erythema nodosum, the most common form, is a septal panniculitis without vasculitis, typically on the anterior shins.

Erythema induratum is a lobular panniculitis with vasculitis, strongly associated with tuberculosis.

Pancreatic panniculitis shows ghost-like fat cells from enzymatic fat necrosis due to pancreatitis or carcinoma.

Alpha-1 antitrypsin deficiency can cause a neutrophilic lobular panniculitis.

Diagnosis requires a deep excisional biopsy to adequately sample the subcutaneous fat.

The key histologic distinction is septal versus lobular inflammation.

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Panniculitis