Interstitial Granulomatous Dermatitis With No Neutrophilic Infiltrate

To the Editor: Interstitial granulomatous dermatitis (IGD) is a rare disorder first reported with arthritis.1 Its pathognomonic sign, the rope sign, is a linear prominent cutaneous band on the trunk. Subsequent accumulation of cases has shown that IGD rarely shows the rope sign; moreover, its association with arthralgia or arthritis is not always found, and approximately half of the cases have autoantibodies.2 Histologic features comprise collagen degeneration associated with a dermal band-like infiltrate composed mainly of histiocytes.3 Neutrophils and eosinophils are also present in the infiltrate; however, usually no vasculitis is seen.3 In this study, we report a case of IGD with no neutrophilic infiltrate. A 60-year-old woman presented with a 3-year history of asymptomatic cutaneous eruption on the left lateral trunk, which also developed on the right lateral trunk 1 month before. The patient experienced idiopathic thrombocytopenic purpura (ITP) for 13 years, which was well-controlled with 1 mg of prednisolone every 10 days with a normal platelet count. A physical examination revealed linear erythematous bands on the bilateral trunk (Fig. 1). Biopsy was performed on the lesion on the left lateral trunk, and it revealed reticular dermal mixed inflammatory infiltrates centered on hyalinized and degenerated collagen bundles with histiocytes (Fig. 2). Dense perivascular lymphocytic infiltrates surrounded the lesion (Fig. 2A). Alcian blue and colloidal iron stains did not reveal mucin deposition. No neutrophils, frank vasculitis, or granuloma formation was identified. Based on the typical clinical features of the rope sign and histopathologic findings, the patient was diagnosed with IGD. Although further investigation revealed positive anti-SSA and anti–double-stranded DNA autoantibodies, the patient showed no symptoms and was not diagnosed with any collagen vascular diseases. The lesion became slightly dark reddish because of potent topical corticosteroids; nonetheless, it remained stable for 1.5 years.FIGURE 1.: A and B, Linear erythematous bands on the bilateral trunk.FIGURE 2.: A, Degenerated collagen bundles were surrounded by dense perivascular lymphocytic infiltrates in the mid and deep dermis [hematoxylin–eosin (HE), original magnification ×20]. B, Degenerated collagen bundles were surrounded by histiocytes. Neutrophilic infiltrate was not recognized (HE, ×200). C and D, CD68 staining highlighted an increased number of histiocytes in the lesion [CD68, (C) ×20, (D) ×200].IGD is histopathologically characterized by lesions showing interstitial inflammatory infiltrates composed of histiocytes and lymphocytes, with surrounding foci of collagen degeneration with neutrophils and eosinophils.4 Vasculitic changes are absent, and mucin deposits are minimal or absent. Coutinho et al4 studied 10 cases of IGD, and all cases showed mild, moderate, or heavy neutrophilic infiltrate. We first hesitated to make a histopathologic diagnosis of IGD because of no neutrophilic infiltrate. However, the typical clinical manifestation suggested IGD, and we realized that neutrophils are occasionally absent in IGD. Verneuil et al3 asserted that histopathologic findings of IGD differ according to the stage of the lesions at the time of biopsy. Early-stage lesions show a pandermal neutrophilic infiltrate, whereas fully developed lesions show scattered leukocytes.3 This case may be the end stage of IGD, considering the lack of neutrophilic infiltrate. IGD is often confused with palisaded neutrophilic and granulomatous dermatitis (PNGD), which exhibits larger foci of basophilic or eosinophilic collagen degeneration and more prominent neutrophilic infiltrates, with or without leukocytoclastic vasculitis.4 Mucin deposits are also scant or absent. IGD and PNGD present with similar clinical manifestations, including erythematous plaques/macules, annular plaques, and papules/nodules.2 The rope sign is a rare manifestation of both diseases.2 Some studies also suggest that IGD and PNGD are overlapping disease entities on a continuum based on the cases showing overlapping histopathologic and clinical features of IGD and PNGD.2,5 Regarding PNGD, Chu et al6 reported that early-stage lesions show diffuse pandermal neutrophilic infiltrate, fully developed lesions show a diminished number of neutrophils, and older lesions show scattered neutrophils. Taken together, an abundant neutrophilic infiltrate in an early stage in both IGD and PNGD may decrease according to the disease course and eventually may be depleted. The rope sign has been described in less than 10% of patients with IGD and PNGD, and it is usually associated with autoimmune disorders.2 ITP has never been reported as a disease associated with IGD or PNGD. Because the patient's ITP was well-controlled when IGD developed, the possibility that ITP and IGD were coincidental cannot be denied. Although half of IGD and PNGD lesions disappear within a few weeks, the lesions persist over the years in the rest of the patients despite various treatments.2 The lesions in this case are also refractory to the treatment. Refractory lesions may be associated with the absence of neutrophilic infiltrate because such lesions have a long disease course. Other differential diagnoses are granuloma annulare (GA) and interstitial granulomatous drug eruption. Although a low-power view of our case showed similarity to a palisaded pattern, GA was denied because of no increase in mucin.7 According to a recent review of interstitial GA, interstitial mucin is scant or absent in interstitial GA.7 However, interstitial GA is characterized by a relatively normal-appearing dermis on scanning magnification, with a slight increase in cellularity.7 In our case, it is not so. Interstitial granulomatous drug eruption is caused by specific drugs such as angiotensin-converting enzyme inhibitors, anticonvulsants, antidepressants, antihistamines, anti-tumor necrosis factor agents, beta-blockers, diuretics, herbal medications, immune checkpoint inhibitors, and lipid-lowering agents.8 Because ITP in our patient was treated with prednisolone with gastric-coating agent and vitamin D3 preparation, the possibility that our patient developed interstitial granulomatous drug eruption was denied. In addition, no interface reaction was detected at the dermoepidermal junction in our case despite the presence of interface dermatitis as a characteristic feature of interstitial granulomatous drug eruption.9