Phalange osteolysis present as the initial manifestation of sarcoidosis in a young female

Introduction

Sarcoidosis is a systemic granulomatous disease, the etiology and pathogenesis of which remain unclear. Its pathological characteristics are primarily noncaseating necrotizing epithelioid cell granulomas. ¹ The condition is often misdiagnosed due to the involvement of multiple organs, variable symptoms, and low morbidity. This disease predominantly affects young and middle-aged individuals, with a slightly higher prevalence in women compared to men. The lungs and intrathoracic lymph nodes are the most commonly affected sites, followed by the skin, liver, eyes, and nervous system. ² Sarcoidosis affects the musculoskeletal system in only 5%–10% of cases.

We report the case of a patient who presented with swelling of the left ring finger lasting for more than 6 months. She was initially suspected to have a malignant bone tumor by her orthopedic team. Pathological examination revealed granulomatous inflammation in the phalanges and mediastinal lymph nodes, leading to the diagnosis of sarcoidosis. In addition, we reviewed the differential diagnoses of bone sarcoidosis to improve clinicians’ understanding of the disease and reduce the risk of misdiagnosis.

Case presentation

A 22-year-old woman presented to the orthopedic clinic with a complaint of swelling in her left ring finger that had persisted without any obvious cause for more than 6 months. She reported no numbness or pain in the affected finger.

On examination, the distal joint of the left ring finger was swollen and slightly tender, with a normal blood supply and proprioception.

The patient had a history of urticaria for over 4 years and denied any history of tuberculosis infection or food or drug allergies. The patient had no relevant family history.

High-resolution computed tomography (CT) imaging of the left hand revealed expansion of the distal left ring finger, local bone absorption and destruction, multiple cystic low-density areas, and no significant abnormal surrounding soft tissue shadows (Figure 1). The remaining bones of the left hand depicted no signs of hyperplasia or destruction. The joint spaces were clear, and the joint surfaces appeared smooth.

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Figure 1.

X-ray, CT, and MRI images of the left hand. Anterior-posterior (a) and lateral (b) projections of the left ring finger depicting the enlarged proximal end with local bone absorption and destruction as well as multiple cystic low-density areas (red arrow). The insertion in (a) is the high-resolution CT transverse section. MRI depicting the abnormally long T1 (c) and T2 (d) signals along with the transverse section inserted in (c) revealing expansion on the dorsal side of the proximal end of the left ring finger (red arrow).

Magnetic resonance imaging of the left hand revealed abnormally long T1 and T2 signals in the proximal region of the left ring finger, with expansion toward the dorsal side. Local cortical signals were unclear, but no significant abnormalities were observed in the surrounding soft tissues (Figure 1).

Whole-body bone scintigraphy revealed no abnormalities in any of the remaining bones.

Chest contrast CT revealed a mass shadow in the right hilum, multiple lymphadenopathies in the mediastinum and hilar regions, as well as multiple small nodules in both lungs (Figure 2).

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Figure 2.

Contrast-enhanced chest CT images depicting a mass shadow (a, red arrow) in the right hilus, multiple small nodules in both lungs and multiple lymphadenopathies in the mediastinum and both hilae (b–d, red arrows).

Given the swelling of the distal phalange accompanied by bone resorption and cortical destruction, tumors or tumor-like lesions were suspected. Consequently, her orthopedist performed an incisional biopsy and bone grafting.

Histopathological analysis revealed lymphocyte and neutrophil infiltration accompanied by extensive epithelioid cell reactions and small focal necrosis, consistent with granulomatous inflammation (Figure 3). Immunohistochemical findings included CD68 (+), scattered S-100 (+), occasional CD1α (weak +), SMA (−), Desmin (−), partial Caldesmon (+), CD34 (−), CK (−), acid-fast staining (−), periodic acid-Schiff (PAS) stain (−), and reticular fiber (−).

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Figure 3.

Histopathology depicting lymphocyte and neutrophil infiltration with numerous epithelioid reactions and small focal necrosis in the phalanges (a, b: hematoxylin–eosin staining; a: magnification ×5; b: magnification ×20) and mediastinal lymph nodes (c, d: hematoxylin–eosin staining; c: magnification ×5; d: magnification ×40).

The patient was referred to a pulmonary physician for endobronchial ultrasonography and transbronchial needle aspiration. Tuberculosis X-pert testing of the bronchoalveolar lavage fluid yielded negative results. Pathological examination of the subcarinal lymph nodes revealed epithelioid cell aggregation in the blood clot without necrosis, consistent with granulomatous inflammation (Figure 3). Acid-fast staining and PAS results were negative, whereas reticular staining was positive.

The patient was diagnosed with stage II sarcoidosis, complicated by bone involvement. She was prescribed prednisone tablets at a dosage of 30 mg orally, once daily. After 4 weeks, the dosage was reduced to 15 mg orally, once daily.

Follow-up chest CT performed 2 months later revealed a significant reduction in the size of the hilar and mediastinal lymph nodes, indicating effective treatment. The phalanges healed well, and no recurrence was observed.

Discussion

Sarcoidosis was first reported by Hutchinson in 1877 as the presence of multiple nodules on the skin. In 1889, Boeck described it as “multiple benign sarcoidosis of the skin,” and it later became known as sarcoidosis. Although over a century of research has enhanced our understanding of sarcoidosis’s immune mechanisms, associated genetic loci, pathological features, and clinical manifestations, its exact cause remains unclear. ³ It is currently believed that genetic susceptibility, combined with interactions with environmental factors, plays a central role in sarcoidosis development. Sarcoidosis occurs all over the world, with a prevalence rate of 4.7–64 cases/100,000 people. ⁴ Since there are no definitive clinical diagnostic criteria, the diagnosis requires a comprehensive evaluation of the clinical symptoms of the patient, radiological findings, and pathological biopsy results, such as the presence of noncaseating necrotizing epithelioid cell granulomas. This must be combined with the medical history of the patient and serological findings, as sarcoidosis can only be diagnosed after excluding other granulomatous diseases. ⁵

In the present case, the patient presented with swelling of the left ring finger.

Histopathological examination revealed granulomatous inflammation in the distal phalanx of the fingers and mediastinal lymph nodes. Sarcoidosis diagnosis was confirmed after ruling out other granulomatous diseases such as tuberculosis, nontuberculous mycobacterial infection, chronic candidal infection, and so on.

The organs most commonly affected by sarcoidosis are the lungs and intrathoracic lymph nodes, which account for ~90% of the cases. It can also affect the skin, eyes, heart, nervous system, and other organs of the body. Skin involvement in sarcoidosis occurs in ~20%–35% of patients, with lesions typically present at the time of diagnosis. The most common nonspecific skin manifestation is erythema nodosum.

The most common manifestation of ocular lesions is uveitis, which occurs in 10%–60% of cases and can severely threaten vision. Therefore, all patients diagnosed with sarcoidosis should undergo ophthalmological evaluations. Cardiac involvement can present as arrhythmias or heart failure. ² Approximately 5% of patients with sarcoidosis experience nervous system involvement, with cranial nerve damage being the most common complication. When the facial nerve is affected, sudden facial paralysis may occur. If the optic nerve is involved, the patient may experience blurred vision. In addition, there have been case reports of olfactory impairment caused by granulomas affecting the olfactory nerve.

Bone involvement in sarcoidosis is rare, with studies indicating that 3%–13% of patients with sarcoidosis experience skeletal involvement. ⁶ The low prevalence may be related to the fact that most patients with osseous sarcoidosis are asymptomatic and underdiagnosed. ⁷ The majority of osseous sarcoidosis is discovered incidentally for other reasons rather than due to symptoms suggesting osseous sarcoidosis. The most commonly affected bones are those of the hands and feet, typically presenting as swelling of the fingers or toes. The ulna and femur are also affected. However, with the increasing use of ¹⁸F-FDG PET/CT imaging recently, it has been found that more than 80% of patients with osteo-sarcoidosis have axial bone involvement, while appendicular bone involvement remains relatively rare.^8,9 Consequently, it is recommended that patients with sarcoidosis undergo ¹⁸F-FDG PET/CT for a comprehensive evaluation, as this imaging technique can help assess both bone involvement and damage to other organs. ¹⁰

Typical imaging manifestations of osteo-sarcoidosis include osteolytic and bone cystic changes, punctate lesions, trabecular bone abnormalities, and sclerosis in some patients. When small bones such as those in the hands and feet are involved, imaging often depicts lacy trabecular patterns or granulomatous perforated transparent lesions. In cases where larger bones are affected, severe cortical bone destruction may occur. However, periosteal reactions are uncommon, distinguishing osteo-sarcoidosis from bone tumors.

Osteo-sarcoidosis should be differentiated from other conditions that can cause bone enlargement or destruction, such as giant cell tumor of the bone, bone tuberculosis, and certain metabolic bone diseases, including Paget’s disease of the bone and hyperparathyroidism.

A giant cell tumor of the bone is a primary bone tumor that typically occurs at the ends of long bones in the limbs. ¹¹ Its imaging manifestations are diverse, with the most typical features being expansive growth and bone shell formation. Edge sclerosis may also be present without periosteal reaction, and osteolytic destruction can involve the bone cortex along with bone cystic degeneration. These characteristics closely resemble those of osteo-sarcoidosis, making differentiation challenging.

The most common site affected by bone tuberculosis is the spine, where imaging changes are distinct. These include calcification of the affected vertebral body, paravertebral abscesses, spinal canal involvement, bone destruction, and narrowing of the vertebral space.

Paget’s disease of bone most commonly affects the pelvis but can also involve the axial skeleton and proximal femur. ¹² This disease is characterized by abnormal osteoclastic and osteoblastic activity, leading to accelerated bone turnover and irregular new bone deposition. ¹³ X-ray imaging typically demonstrates cortical thickening, trabecular thickening, and bone enlargement. ¹⁴

Hyperparathyroidism affects all bones of the body. ¹⁵ The clinical manifestations include generalized bone pain and pathological fractures. On imaging, it may present as osteoporosis, bone resorption, or fibrocystic osteitis. The characteristic brown tumors observed on CT scans are suggestive of hyperparathyroidism.

In cases where imaging findings are atypical, a biopsy can be performed at an abnormal site. Pathological examination combined with relevant serological indicators can assist in the diagnosis and differentiation of hyperparathyroidism.

Sarcoidosis can also affect joints. Previous studies have found that the incidence of joint involvement in sarcoidosis is ~20%, with a higher prevalence among middle-aged women. Clinical manifestations include joint pain, tenderness, swelling, and limited movement, typically affecting fewer than four joints. As some patients may be asymptomatic, the true incidence of joint involvement may be underestimated. Joint involvement was most commonly observed in the ankle joint (42%), followed by the knee joint (33%), hand joint (25%), and more rarely, the sacroiliac and hip joints.

Current guidelines recommend that the treatment of pulmonary sarcoidosis should be based on the clinical manifestations of the patient, underlying conditions, and the severity and activity of the disease. The goal is to alleviate symptoms, improve patient’s quality of life, and delay the occurrence and progression of complications.

Treatment should be initiated when patients with sarcoidosis experience a significant decline in quality of life or an increased risk of disability and fatality.^16,17 Treatment is necessary for patients with notable respiratory symptoms, such as cough, progressive dyspnea, or chest pain; systemic symptoms, such as fatigue, fever, and weight loss; progressive deterioration of lung function; worsening intrapulmonary shadows; or significant extrapulmonary organ involvement, including the heart, nervous system, eyes, and liver. When bone involvement occurs in sarcoidosis, it typically indicates multiple organ involvement or high disease activity, and active treatment of osteo-sarcoidosis is recommended.

Systemic glucocorticoids are typically the first choice of treatment for patients with sarcoidosis. The starting dose is usually prednisone (or an equivalent dose of other corticosteroids) at 0.5 mg/kg/day, or 20–40 mg/day. The dose was gradually reduced over 2–4 weeks and maintained at 5–10 mg/day, with the total treatment duration ranging from 6 to 24 months. For patients for whom steroids are ineffective, whose condition recurs or worsens after dose reduction, or who are intolerant to steroids, immunosuppressive therapy may be considered. Options include methotrexate, azathioprine, mycophenolate mofetil, leflunomide, and biological agents such as infliximab, adalimumab, and rituximab. Lung transplantation may be the only effective treatment for end-stage pulmonary injuries.

Currently, there is no consensus on the treatment of osteo-sarcoidosis. However, most patients treated with glucocorticoids have favorable prognoses. For those who do not respond well to hormone therapy, immunosuppressants, or biological agents, as mentioned earlier, may help improve the condition.^17,18

There are also case reports indicating that non-steroid anti-inflammatory drugs alone can successfully alleviate pain symptoms and imaging abnormalities in patients with osteo-sarcoidosis. ¹⁹ Recently, studies have reported that Janus kinase inhibitors can improve the clinical symptoms of osteo-sarcoidosis, with patients’ conditions being effectively controlled after treatment with tofacitinib. ²⁰ After initiation of hormone therapy, outpatient follow-up revealed its effectiveness. A review conducted after 8 weeks depicted significant shrinkage of the hilar and mediastinal lymph nodes, and no bone damage was detected on the bone (99m) Tc-MDP bone scanning.

In summary, although sarcoidosis can affect multiple organs and tissues throughout the body, joint damage is rarely the initial manifestation. Its clinical and imaging features lack specificity, making it challenging for clinicians to arrive at a rapid diagnosis. There is no objective diagnostic standard for sarcoidosis, and in clinical practice, it is often a diagnosis of exclusion. In addition to considering the clinical characteristics and imaging findings, it is crucial to combine pathological evidence and exclude similar diseases before confirming the diagnosis. This case emphasizes the importance of improving clinicians’ understanding of osteo-sarcoidosis. When patients present with granulomatous bone lesions, sarcoidosis should be considered, and further examinations should be conducted to avoid misdiagnosis or missed diagnoses.