Granulomatous Inflammation in Alopecia Areata: A Diagnostic Pitfall

Dear Editor, Alopecia areata (AA) is a common, nonscarring alopecia caused by an autoimmune T-cell-mediated attack on anagen hair follicles.[1] However, granulomatous inflammation in association with AA is an exceptionally rare finding and may lead to diagnostic confusion. A 27-year-old man presented with patchy hair loss for past 3 months. There were no systemic complaints. Examination revealed a well-defined solitary patch of alopecia on occipital scalp [Figure 1a]. Dermoscopy (Heinz Delta30, 10x) showed background erythema with numerous brown dots [Figure 1b]. Rapid plasma reagin and antinuclear antibody tests were non-reactive. Mantoux test was negative, and angiotensin - converting enzyme levels and chest radiography were within normal limits. Histopathology revealed perifollicular lymphohistiocytic granulomatous inflammation with destruction of hair follicles [Figure 2a and 2b] with sheets of multinucleated giant cells replacing follicle [Figure 2c]. Special stains including Ziehl-Neelsen, Gram, Gomori’s methenamine silver, and periodic acid-Schiff, were negative. The patient was diagnosed with AA with granulomatous inflammation and was treated with intralesional triamcinolone (10 mg/mL). Complete hair regrowth was observed on follow-up at 2 months [Figure 3a and 3b].Figure 1: (a) Well-defined solitary patch of alopecia of size 2.5 × 2.5 cm on the occipital scalp. (b) Dermoscopy showing background erythema with numerous brown dots. (Heinz Delta30, 10x magnification)Figure 2: Histopathology revealed perifollicular lymphohistiocytic granulomatous inflammation with the destruction of hair follicles mainly in the deeper dermis (a) (Hematoxylin and eosin, 40x), (b) (Hematoxylin and eosin, 100x). Sheets of multinucleated giant cells replacing the follicle (c) (Hematoxylin and eosin, 400x)Figure 3: Complete regrowth of hair after intralesional triamcinolone injection (10 mg/mL) (a) Clinical photograph (b) Dermoscopy showing multiple terminal hairs with whitish, structureless area (biopsy site) (Heinz Delta30,10X magnification)Granulomatous inflammation in AA represents an uncommon finding first described by Mondolfi et al., who reported two cases showing prominent peribulbar granulomatous inflammation in the absence of infectious, systemic, or foreign-body causes.[1] Subsequent reports have supported this rare histopathologic pattern, suggesting that granulomatous inflammation may occur within the AA spectrum, rather than representing a distinct entity.[2-4] The pathogenesis of granuloma formation in AA remains speculative. It has been proposed that disruption of hair follicle immune privilege due to trauma or rupture of hair follicles may expose normally sequestered follicular antigens to immune surveillance, triggering a Th1-mediated foreign body-type granulomatous reaction.[1] The shift from a predominantly lymphocytic infiltrate to a granulomatous one may therefore reflect chronic or exaggerated immune activity directed against follicular components. Of the four published cases of granulomatous AA, two revealed the destruction of hair follicle with granulomatous inflammation on histopathology,[2,3] while the other two did not show follicular destruction.[1,4] These observations signify that secondary foreign body-type granulomatous inflammation may have occurred in the former cases, whereas granulomatous inflammation seen in latter cases may be due to a primary pathology.[1-4] Clinically, AA with granulomatous inflammation is indistinguishable from conventional AA, and typically presents as smooth, well-demarcated patches of nonscarring alopecia. Histopathology is essential for diagnosis and for differentiating this entity from other granulomatous alopecias such as sarcoidosis, syphilis, leprosy, or lupus miliaris disseminatus faciei. The granulomas in granulomatous AA are usually localized to the peribulbar region, often admixed with lymphocytes and occasionally containing eosinophils or plasma cells, while the upper follicle remains uninvolved - an important clue distinguishing it from scarring alopecias such as lichen planopilaris and folliculitis decalvans.[2,4] Sarcoidal-type granulomas have also been described without prominent lymphocytic infiltration, emphasizing the histologic variability within this spectrum.[4] Plasma cells and eosinophils were not observed in the present case; instead, a predominant peribulbar lymphohistiocytic granulomatous infiltrate was noted. The presence of granulomatous inflammation in AA can be a diagnostic pitfall, especially in regions where infectious granulomatous disorders, such as tuberculosis, leprosy, and syphilis, are common. Therefore, careful clinicopathologic correlation and exclusion of infectious causes are essential. Treatment is similar to that of conventional AA, including topical or intralesional corticosteroids. In some cases, systemic agents, such as tofacitinib, have been used with successful hair regrowth.[1,4] Recognition that granulomatous inflammation may rarely occur secondary to follicular destruction in AA is important to prevent overdiagnosis of infectious or systemic granulomatous disorders and to avoid unnecessary investigations. Clinicians should be aware of this uncommon histopathologic manifestation of AA which may lead to a diagnostic dilemma. Authors’ contributions We confirm that all authors have read and approved the manuscript for submission. All authors meet authorship criteria, and the manuscript represents honest work. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.