Ⅰ. INTRODUCTION

Acneiform eruptions are a group of skin conditions that clinically resemble acne vulgaris but lack typical comedonal (hair follicle-blocked) features and may occur beyond the usual age range for acnes vulgaris¹. Various skin diseases can present as acneiform eruptions with granulomatous components including granulomatous rosacea, perioral granulomatous dermatitis, cutaneous sarcoidosis, granuloma annulare, idiopathic facial aseptic granulomas and demodicosis ^2-6. While some granulomatous components arise as secondary responses to hair follicle destruction, systemic and genetic chronic granulomatous disorders can also mimic acneiform lesions, indicating that the granulomatous variants of acneiform eruptions are distinct pathologic entities^2,7-9.

Granulomatous variants share some clinical features with other types of acneiform diseases but have the distinct histopathological features, the presence of granulomas within the lesion. These variants commonly involve hair follicle units with histopathologic features of follicular rupture and destruction ³. This is not surprising, as the hair follicle niche nourishes commensal microorganisms’ potential for infectious or immune granuloma initiation. A well-known example is Cutibacterium acnes (formerly termed Propionibacterium acnes), which has been implicated in granulomatous disorders such as sarcoidosis and lupus miliaris disseminatus faciei^10-12.

However, hair follicle involvement is not always necessary for granulomatous acneiform inflammations. Systemic granulomatous infections or chemical agents can induce cutaneous lesions independently of the follicular unit. In the case of localized acneiform eruptions, subdermal or interstitial foreign materials close to the clinical manifestations may be causal factors rather than follicular microorganisms¹³.

Here, we present a case of C. acnes-induced facial acne-like (acneiform) granulomas that were refractory to routine long-term antibiotics. Interestingly, the dermal granulomas were adjacent to but did not include the local hair follicles or skin appendages, suggesting an alternate anatomical source for the infection. We identified intracellular C. acnes within distant dental lesions, supporting the hypothesis that odontogenic infection may play a role in triggering facial granulomatous acneiform eruptions. This case highlights the need for dental evaluation in patients with acneiform granulomas that do not respond to conventional antibiotic treatment.

Ⅱ. CASE REPORT

A 56-year-old male presented with multiple papules and skin rashes on his lower lip and chin, which had persisted for over 18 months. Previous medical institute had diagnosed the lesions as cutaneous granulomas through skin biopsy, and the patient was treated with unspecific antibiotics and steroids for more than a year, without significant improvement. He had no known medical conditions or history of medication use.

At his initial visit to our hospital, the patient exhibited localized erythema and mild swelling on the skin of the lower lip, vermillion border, and mid-chin, along with multiple indurated papules resembling acne with rosacea (Fig. 1A). Given that our institute is a dental hospital, we conducted a comprehensive oral examination. No mucosal or structural abnormalities were found in the oral cavity, except for the lower left first molar, which showed gingival swelling, redness, and pus discharge. The problematic tooth had a history of endodontic root canal filling and exhibited a well-defined osteolytic apical lesion recognizable on panoramic x-ray, suggesting localized apical periodontitis.

Ⅲ. RESULTS

To reassess the pathogenic course of the disease, we performed a second biopsy on lower lip lesions. Both the initial and second biopsies revealed diffuse inflammation infiltrating the edematous superficial and mid-dermis (Fig. 2A, 2C, respectively). The inflammatory infiltrates were organized into non-caseating tuberculoid granulomas, concentrated along numerous dilated vascular and lymphatic structures (Fig. 2B, 2D), likely contributing to the rosacea- like clinical manifestations. The tuberculoid granulomas were composed of epithelioid histiocytes and Langhans-type multinucleated giant cells, surrounded by rich collections of lymphocytes.

Although these lesions were inflammatory tuberculoid granulomas rather than ‘naked’ sarcoid granulomas, we conducted ancillary tests targeting C. acnes to rule out the possibility of cutaneous or systemic sarcoidosis^10-12. Periodic acid-Schiff (PAS) and acid-fast stains were negative, excluding fungal organisms and mycobacterium, respectively. To our surprise, the biopsy specimen stained positive using a PAB antibody, which specifically reacts to the lipoteichoic acid (LTA) antigens found in the membrane of C. acnes¹². The PAB antibody was positively stained as multiple cytoplasmic aggregates within granuloma-associated mononuclear macrophages, but was not in the multinucleated giant cells (Fig. 2E). To further confirm the presence of bacterium, we performed polymerase chain reaction (PCR) on the biopsy specimens, which detected the 16s rRNA gene of C. acnes. It revealed a positive band of C. acnes, but neither for Mycobacterium tuberculosis nor Propionibacterium granulosum (Fig. 2F). These findings suggested that persistent C. acnes infection as the potent cause for the acneiform dermal granulomas.

We prescribed minocycline, a tetracycline-class antibiotic commonly used for C. acnes-related diseases like sarcoidosis and acne vulgaris^11,14,15. Although the lesions initially showed mild improvement, but soon recurred, remaining as persistent inflammatory lesions similar to those observed at the patient’s first visit (Fig. 1B). We hypothesized that the poor response could be due to either minocycline-resistant or the inability of antibiotics alone to eradicate the underlying infection. Therefore, we searched for an alternative infectious source of C. acnes infection throughout the patient’s body. The inflamed tooth (lower left first molar) was the only anatomic site showing active inflammatory manifestations. Given the poor bone support of the tooth and the active state of apical periodontitis (Fig. 1E-1G), it was extracted with the patient’s consent. The apical lesion was sent to the lab for further investigation.

The odontogenic specimen revealed intermixed edematous and fibrous inflammatory tissue (Fig. 2G). Changes in vascular or lymphatic structure were inconspicuous except for mild angiogenesis within the granulation tissue. The inflammation was composed of lymphoplasmacytic infiltrates, activated macrophages, and a few neutrophils, histopathologic findings commonly seen in odontogenic inflammations. A few of the macrophages were suspected of presenting epithelioid or multinuclear-like morphological transformations, but the macrophages were predominantly mononuclear cells with abundant cytoplasm and indistinct cell margins (Fig. 2H). The specimen lacked evidence of definite mature granuloma formation. Upon PAB antibody staining, positive cytoplasmic aggregates were seen in fractions of the activated macrophages (Fig. 2I), identical to the dermal specimen. On PCR analysis the odontogenic specimen showed consistency with the dermal specimen, positive for C. acnes while negative for M. tuberculosis and P. granulosum (Fig. 2J). The distantly located facial (dermal) and odontogenic (dental) inflammations, regarded as solitary and distinct lesions, both contained activated macrophages with intracellular C. acnes, a bacterium known for its phagocytic resistance and granuloma formatting abilities^16-18.

The facial acneiform eruptions, redness, and swelling showed significant improvement at 2 months after tooth removal (Fig. 1C). By 10 months post-extraction, the skin lesions had nearly resolved, leaving only a few faint red streaks on the chin (Fig. 1D). The extraction socket healed normally without any postoperative complications. Minocycline was continued throughout the surgical intervention and follow- up period, with no additional side effects reported¹⁹.

Ⅳ. DISCUSSION

Chronic inflammatory disease associated with C. acnes is a recognized pathogenic event, yet our case provides new insight into C. acnes’ pathogenesis and the potential role of an oral-skin microbiome axis. This case suggests that persistent infections in the skin and oral cavity may not only share a common causative microorganism but may also interact along this axis, influencing clinical outcomes. It is well known that intraoral agents can induce cutaneous manifestations through direct anatomical connection, such as in orofacial fistulas, or diffuse hypersensitive immune reactions that involve vast regions in the head and neck region^19,20. In contrast, our case had separate C. acnes-infected chronic inflammatory diseases which were regarded as clinically unrelated.

Determining whether the skin or oral cavity can be the infectious origin for the other side remains a difficult and controversial issue. C. acnes is a commensal anaerobe in both the skin and oral cavity, so shared bacterial involvement in both lesions may be regarded as a coincidence^18,21-24. Previous study has found C. acnes to be the prevalent microorganism in apical periodontitis with ‘open communication’ to the oral cavity, unlike in isolated apical infections²⁴. The apical lesion in this case was open to the gingival surface, with evidence of periodontal pus discharge and had a history of root canal treatment, consistent with other C. acnes-related apical infections^24,25. C. acnes of skin commensals and refractory apical periodontitis also share dominant phylogenetic strain types, particularly type I, which makes skin and oral strain distinguishment more challenging²⁴. While some reports suggest that C. acnes in apical periodontitis could be a nosocomial contaminant introduced during dental procedure, cutaneous granulomas may have acquired their intracellular C. acnes from direct lymphatic transmissions or through phagocytic carriers^12,24-29.

Regardless of whether causality exists between oral and skin infections and their progressive direction, our case implies that there may be an oral-skin-C.acnes axis which critically influences clinical outcomes on both anatomical sites. Notably, the facial granulomatous inflammation remained refractory to minocycline until the infected tooth was removed. This finding highlights the importance of managing odontogenic infections through invasive dental interventions, such as root canal therapy, curettage or tooth extraction, especially since the antibiotics alone may be ineffective in communicated odontogenic infections^29-32. Root canals, particularly necrotic or avascular (due to root canal filling) in apical periodontitis, provides a sanctuary for anaerobic bacterium^33-36. An infected root canal may constantly supply pathogenic bacterium to the adjacent soft tissue because of its poor access to systemic and local antibiotic delivery. The removal of the inflamed tooth, a potential bacterial chamber, seemed to accelerate healing in both facial and oral infections and normalize the antibiotic effects of minocycline therapy.

Based on our findings, treating relevant odontogenic infections could improve the clinical outcomes of antibiotic therapy in chronic inflammatory skin diseases, especially those affecting the lower face. Further clinical studies and molecular investigation are needed to clarify the role of C. acnes pathogenesis in the oral-skin-microbiome axis and acneiform skin diseases. We advise dermatologists and dentists to include a dental examination in idiopathic facial dermatitis and granulomatous inflammations refractory to regular antibiotic therapeutics.

Ⅴ. CONCLUSION

Our case highlights a possible oral-skin-C. acnes axis, suggesting that persistent infections in the oral cavity can influence the clinical course of facial granulomatous acneiform eruptions. Minocycline alone was insufficient to resolve the patient’s skin lesions until the infected tooth was extracted, emphasizing the importance of evaluation and managing odontogenic infections in tandem with dermatologic area.