Multicentric reticulohistiocytosis (MRH), a subtype of non-Langerhans cell histiocytosis, involves abnormal proliferation of histiocytes, a type of immune cell, in various tissues and organs [1]. It is a chronic and progressive disease, and the exact cause is not yet fully understood. Infiltration of histiocytes can be observed in the skin and joints of the extremities, such as the hands and feet. This condition typically affects adults, particularly women, and can cause skin nodules, joint pain, and deformity. Other manifestations involving the heart, lung, or mucous membrane have been described in some cases. Mucosal lesions involving the esophagus and oral cavity may cause dysphagia [2]. However, organs other than the skin and joints are relatively rarely involved.

MRH has been reported in less than 300 individuals worldwide; thus, large-scale studies do not exist. Most of the reports on MRH describe systemic inflammation of the skin and joints, which is a characteristic feature of the disease [2]. Only a few reports have described the involvement of tissues or organs other than the skin and joints of the hand and foot in MRH. Descriptions in relation to dental manifestations are particularly rare. One such report was published by Yoshimura et al. [3] in 1987, which described a case of MRH in a patient who had gingival hypertrophy and lost multiple teeth following histiocytic infiltration in the gingiva.

Given the scarcity of relevant literature, this study reports the case of a patient who was diagnosed with MRH and subsequently presented with temporomandibular joint (TMJ) involvement to provide in-depth knowledge to clinicians.

This study was approved by the Institutional Review Board (IRB) of Seoul National University Dental Hospital (#ERI23018). The IRB waived the need to obtain informed consent given the retrospective nature of the study.

A 58-year-old woman visited the Department of Oral Medicine with the chief complaint of pain located in the TMJ area on both sides. Two years ago, the patient visited a tertiary hospital for evaluation of leg edema. The examination results ruled out possible rheumatic disease as the cause of leg edema, and medications were started based on the suspicion of a possible autoimmune disease. A few months later, the patient visited the dermatology department of Gangnam Severance Hospital because of pain and skin lesions in the hands and knees. MRH was confirmed through tissue biopsy, and immunosuppressive drugs including hydroxychloroquine sulfate (Oxiklorin) were prescribed. The patient discontinued the medications, and approximately 1 year ago, the patient began experiencing pain in the TMJ along with limited mouth opening. TMJ pain aggravated while lying down because of jaw displacement. This symptom prompted the patient to visit a local dental clinic and was subsequently referred to a larger hospital for further evaluation and treatment.

Clinical examination was conducted following the Diagnostic Criteria/Temporomandibular Disorders (DC/TMD) [4]. The patient showed a maximal mouth-opening range of 36 mm, and no pain was felt at the point of maximum opening. Joint sounds were not detected. The patient did not report pain on palpation of the TMJ or masticatory muscle areas. However, on the bite loading test, she experienced pain in the right joint when she bit on a wooden tongue suppressor on the left side. The range of lateral movement to the right was restricted to 3 mm. Similarly, right joint pain was reported during left lateral movement.

Occlusal examination revealed an Angle class II division 1 occlusal relationship and an anterior open bite with an overjet of 5 mm. Only the posterior molars were occluded. The mouth-opening path was straight. The patient rated joint pain intensity at a level of 5 on a 0-10 numeric rating scale. The patient reported sleep disturbances and reported short durations of only 3-4 hours ours of sleep per night. No subjective symptoms of bruxism or clenching were noted. The patient had pain in multiple sites including the back, arms, and knee. The patient also complained of eating disorders and gastrointestinal irritation.

Radiographic examinations including orthopantomogram, TMJ panoramic view, and cone-beam computed tomography (CBCT) were performed and evaluated by an oral and maxillofacial radiologist. Results are shown in Fig. 1 and 2. The images revealed degenerative changes in both TMJ condyles. The CBCT revealed severe resorption of the mandibular condyle on both sides, resulting in the loss of the original shape of the condyle. The condyle neck was resorbed to such an extent that the condyle and sigmoid notch could not be distinguished. The articular fossa was also affected, and the joint space was excessively widened. Based on the dental records and radiographic examination from the previous visit to our hospital on March 11, 1999, for the extraction of the right lower third molar, no specific findings were observed at that time other than periapical lesions of odontogenic origin. Therefore, it could be inferred that the severe condylar resorption observed in the recent radiographic examinations had occurred in the intervening years.

After the initial visit on November 4, 2022, the patient had two more visits that focused on the management of contributing factors and possible pain relief. As the patient was already taking immunosuppressive medication such as hydroxychloroquine sulfate (Oxiklorin) and arthritis medications including celecoxib (Celebrex) for MRH, no additional medication was prescribed. Further rheumatology testing was suggested; however, the patient declined, so she was referred to the Department of Rheumatology. The patient reported that she was receiving regular check-ups from another tertiary hospital. The patient’s symptoms remained unchanged at the most recent visit (April 6, 2023), and treatment for occlusal instability was recommended but not accepted by the patient. Further radiographic examinations have been scheduled for the next visit to investigate the prognosis regarding bony destruction of the TMJ condyles.

MRH is an uncommon disease that may affect the entire body. A disease similar to MRH was first discovered by Targett in 1897, and in 1937, it was named multicentric reticulohistiocytosis by Goltz and Laymon [5,6]. However, at present, little is known about its pathogenesis and long-term prognosis.

The most common symptoms of MRH are related to the joints and skin. According to the study conducted by Sanchez-Alvarez et al. [7], which reported 24 cases of biopsy-proven MRH from 1980 to 2017, it was found that all patients had both cutaneous (skin-related) and articular (joint-related) symptoms. Cutaneous symptoms were most commonly observed on the face, arms, and hands and occasionally in the oral cavity, whereas joint symptoms were mostly associated with joint effusion and synovitis of the extremities.

A histological diagnosis is the most crucial step in diagnosing MRH [8]. This can be achieved through a skin biopsy, which confirms the presence of dermal infiltration of multinucleated histiocytes. Typically, these cells have a foamy or ground-glass appearance and eosinophilic cytoplasm [9]. Although synovial biopsy has been performed in some cases and has yielded similar results, it is not commonly recommended because of the difficulty in accessing synovial tissue compared with a skin biopsy [7,8]. Laboratory findings are not consistent among studies. According to Luz et al. [10], all their cases tested positive for the histiocytic marker CD68; however, no other type of laboratory examination was helpful in the diagnosis of MRH. In a small number of cases, the erythrocyte sedimentation rate was increased. Signs of anemia were found in 12% and hypercholesterolemia in 5% of the 96 cases. Recent studies have reported CD10 accumulation in patients with MRH, which correlated with the involvement of various inflammatory conditions such as erosive osteolytic processes [11,12].

The association of MRH with autoimmune diseases such as rheumatoid arthritis and Sjogren’s syndrome was reported in approximately 20% of patients [13]. MRH shows distinctive characteristics from rheumatoid arthritis by a more rapid progression of arthritis, more frequent destruction of articular cartilage and bone, and disfiguring arthritis [14]. The most obvious difference is the presence of skin lesions, which are characteristic of MRH, but typically not seen in rheumatoid arthritis. Representative characteristics of skin lesions include brown-reddish to flesh-colored papular nodules of variable sizes located on hands, creating the typical appearance of a “string of pearls.” [2,7].

Malignancy was found in 25% of MRH cases [5,9,10, 15,16]. However, it is typically not diagnosed before the associated malignancy is identified, indicating that MRH rarely occurs before the detection of the malignancy. Due to the absence of a specific malignancy consistently associated with MRH, it cannot be categorized as a definitive paraneoplastic disorder. Furthermore, when the underlying neoplasm is effectively treated, the joint and skin involvement in MRH may not necessarily show improvement or follow a parallel course [17]. This suggests the presence of a complex relationship between MRH and associated malignancies and requires further investigation to better understand its underlying mechanisms and clinical implications.

The treatment of MRH is still unclear, and various approaches have been proposed [18]. The use of non-steroidal anti-inflammatory drugs in the initial and mild disease stages has been discussed; however, the aggressiveness of MRH usually warrants steroids in early stages. Some evidence shows that early use of disease-modifying antirheumatic drugs, such as methotrexate, may be effective in managing the disease. However, further research is needed to determine the most effective treatment strategies for MRH. As dentists, this is another aspect to consider because drug interactions may occur with certain prescriptions for the management of dental conditions. Long-term radiographic follow-up and subsequent occlusal treatment may be necessary because of the severe destruction of the TMJ condyles and the resulting change in occlusion.

The scarcity of reports on MRH in dentistry suggests the lack of awareness of this condition among dental professionals. Consequently, the risk of misdiagnosis or confusion with other conditions is high. However, certain clinical indicators such as the presence of multiple papular nodules on the lips or oral mucosa, as well as destructive bone resorption affecting both condyles, can raise suspicion for MRH. In such cases, the possibility of systemic diseases other than rheumatoid arthritis must be considered, and further radiographic evaluation and diagnostic investigations are needed to establish an accurate diagnosis.

In conclusion, the patients with MRH may present with advanced bony destruction of the TMJ condyles and report pain and dysfunction similar to TMD. Increased awareness about MRH among dental professionals will facilitate early recognition and appropriate management of this rare condition.

No potential conflict of interest relevant to this article was reported.

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

None.

Conceptualization: JWP. Data curation: SJ, JWP. Methodology: JWP. Visualization: SJ. Writing original draft: SJ. Writing review & editing: JWP.