Reddish painful nodules and bullae over legs: Novel presentation of a classical disease

Dear Sir,

A 12-year-old adolescent girl presented with erythematous painful nodules over both legs for 2 weeks duration, preceded by a history of sore throat 1 month back. Cutaneous examination revealed multiple well-defined bright erythematous nodules over the anterior aspect of both legs associated with tenderness [Figure 1]. An incisional biopsy for histopathology was performed with a provisional diagnosis of erythema nodosum (EN) and differentials including erythema induratum and medium vessel vasculitis, and normal epidermis and dermis with predominantly septal panniculitis without any vasculitis were seen [Figure 2a]. The inflammatory infiltrate was mainly composed of neutrophils and a few lymphohistiocytes suggestive of EN [Figure 2b and c]. Chest X-ray was normal, and Mantoux test was negative and serum calcium levels were normal. Anti-streptolysin O titer was raised (500 U/mL [normal <200 U/mL]), suggestive of streptococcal throat infection, so, symptomatic management with tablet indomethacin 25 mg twice daily was done along with tablet azithromycin 500 mg once daily for 5 days. After 1 week, the patient visited again with complaints of clear to hemorrhagic fluid-filled bullous lesions overlying reddish nodules over both legs and feet [Figure 3a and b] and a few nodular lesions over bilateral arms associated with pain and fever. Due to the bullous morphology and acral location, acral sweet syndrome was considered. However, a repeat biopsy from the bullous lesion revealed similar changes consistent with EN (without dermal infiltrate and edema). In view of severe and atypical disease presentation, a detailed workup for connective tissue diseases, infectious causes, and malignancy was done and was non-contributory, so prednisolone 0.5 mg/kg was prescribed. At 2 weeks follow-up, lesions were more-duskier and bruise-like with decreased tenderness and bullae had settled with no new lesions in the past 1 week. Based on the clinical and characteristic histopathology findings, a diagnosis of bullous EN was made.

Close

Figure 1:

Both legs showing multiple symmetrical, well-defined, bright erythematous nodules on the anterior aspect of the legs.

Export to PPT

Close

Figure 2:

(a) Histopathology image shows normal epidermis and dermis (hematoxylin and eosin X4). (b and c) Histopathology image shows subcutis with predominantly septal panniculitis without vasculitis and infiltrate composed of neutrophils and few lymphohistiocytes (hematoxylin and eosin X40, X100).

Export to PPT

Close

Figure 3:

(a) Right leg and foot showing multiple bullae. (b) Left leg showing settled bulla with surrounding ill-defined dusky erythematous macules and nodules.

Export to PPT

EN is a hypersensitivity reaction to antigenic stimuli and can occur following infections, which may be associated with malignancies, intake of drugs, and inflammatory diseases such as Behcet’s disease, sarcoidosis, and inflammatory bowel disease. It has been theorized to result from the deposition of immune complexes in the lumen of vessels in subcutis, while the other thought explains it as a type IV hypersensitivity.^[1] The classical lesions are erythematous plaques and nodules associated with tenderness, commonly present on anterior legs, and may be associated with fever, malaise, and joint pains. The lesions may subside spontaneously over 4–6 weeks.^[2] Other conditions mimicking such presentations are erythema induratum and medium vessel vasculitis. EN is histopathologically characterized by predominantly septal panniculitis without vasculitis, though rarely small to medium vessel vasculitis has been reported.^[3] The early inflammatory infiltrate is of mixed type containing neutrophils, eosinophils, and lymphohistiocytes, and in older lesions, thickening and fibrosis of septa are seen with lymphohistiocytes and giant cells. Meischer’s granulomas radially arranged histiocytes around a central star-shaped cleft, are relatively specific but not pathognomonic findings of EN. While, erythema induratum commonly presents on posterior legs, may be associated with ulceration and atrophic scarring, and is predominantly lobular and granulomatous panniculitis with large to small vessel vasculitis. Polyarteritis nodosa/medium vessel vasculitis usually also has livedo reticularis and/or ulcerations along with painful subcutaneous nodules and is characterized by septal panniculitis with vasculitis with a neutrophilic transmural infiltrate and fibrinoid necrosis of vascular media.^[4,5] Another condition that can simulate this presentation is EN leprosum (ENL), in which other clinical findings suggestive of Hansen’s disease are also seen. Histopathology of ENL is distinct with neutrophilic infiltrate in a background of lepromatous Hansen’s disease with or without lobular panniculitis and vasculitis and special stains may reveal organisms.^[6]

The present case reports a novel presentation of a classical disease. Further literature is required to know any particular associations of this presentation and/or any prognostic differences from the classical disease.