A 27-year-old woman presents with 10 days of fever, arthralgias of the ankles and knees, and malaise. Examination reveals tender, erythematous, warm, poorly demarcated subcutaneous nodules 2–5 cm in diameter symmetrically distributed over the anterior shins (marked **A** in the diagram). The lesions are intensely painful and have evolved from bright red to violaceous over the past week. Chest radiograph shows bilateral hilar lymphadenopathy without parenchymal infiltrates. Deep incisional biopsy through subcutaneous fat reveals septal panniculitis without vasculitis, with Miescher radial granulomas. ASO titer is normal, throat culture is negative, and Mantoux test is negative. ACE level is elevated. Which of the following best describes the pathophysiology of the lesions marked **A**?
A. Type II antibody-mediated reaction with neutrophilic infiltration and ulceration of the dermis
B. Type IV cell-mediated cytotoxic response with epidermal necrosis and lichenoid infiltration
C. Type III immune complex-mediated vasculitis with destruction of dermal and subcutaneous blood vessels
D. Reactive delayed hypersensitivity response manifesting as septal panniculitis without vasculitis, most consistent with Lofgren syndrome (acute sarcoidosis)
Explanation
Why "Reactive delayed hypersensitivity response manifesting as septal panniculitis without vasculitis, most consistent with Lofgren syndrome (acute sarcoidosis)" is right
Erythema nodosum is the most common form of panniculitis and represents a reactive, delayed hypersensitivity response (Type IV). The histologic hallmark is septal panniculitis WITHOUT vasculitis, with Miescher radial granulomas (small clusters of histiocytes around a central cleft). In this case, the clinical triad of erythema nodosum + bilateral hilar lymphadenopathy + migratory polyarthritis + fever, combined with elevated ACE level and negative infectious workup (normal ASO titer, negative throat culture, negative Mantoux), is pathognomonic for Lofgren syndrome, the acute presentation of sarcoidosis. The characteristic evolution from bright red → violaceous → brownish-yellow (erythema contusiformis) over 1–2 weeks without ulceration or scarring is classic. (Bolognia Dermatology 5e Ch 100; Schwartz Erythema Nodosum Clin Dermatol 2007)
Why each distractor is wrong
Type III immune complex-mediated vasculitis with destruction of dermal and subcutaneous blood vessels: This describes vasculitic panniculitis (e.g., erythema nodosum leprosum, polyarteritis nodosa), not classic erythema nodosum. The biopsy explicitly shows septal panniculitis WITHOUT vasculitis, ruling out this mechanism.
Type IV cell-mediated cytotoxic response with epidermal necrosis and lichenoid infiltration: While erythema nodosum is Type IV hypersensitivity, this distractor incorrectly emphasizes epidermal necrosis and lichenoid changes, which are not features of septal panniculitis. Erythema nodosum is a subcutaneous disease, not primarily epidermal.
Type II antibody-mediated reaction with neutrophilic infiltration and ulceration of the dermis: This describes acute pustular or ulcerative dermatoses (e.g., pyoderma gangrenosum, Sweet syndrome), not erythema nodosum. The lesions marked A do not ulcerate and show lymphocytic/histiocytic infiltration, not neutrophilic.
