Keywords
sarcoidosis - bone - granulomatous disease
Sarcoidosis is an autoimmune disorder of unknown etiology with noncaseating granulomatous
inflammation and multiple organ and system involvement. It is more common in individuals
younger than the age of 50 years with a slight predominance in females.[1] While involvements of lungs, respiratory system, and skin are more common, multiple
involvement of lymph nodes, salivary glands, eyes, musculoskeletal system may also
be seen. The pathophysiology of the disease is not exactly discovered and the diagnosis
is made after pathologic investigations. Bone involvement of sarcoidosis is first
described by Kreibich after detecting multiple radiolucent areas in distal phalanges
of second finger in four patients in 1904.[2] Bone involvement of sarcoidosis is generally asymptomatic and its frequency ranges
from 3 to 13%.[1]
[3] Bone involvement may be lytic, sclerotic, or mixed type.[4] Radiologic findings include the appearance of well-demarcated cysts without any
periosteal reaction and no peripheral sclerosis.[1] The disease involves mostly phalanges in the skeletal system, forming dactylitis.
The involvement may also be present in maxilla, skull, facial bones, vertebrae, ribs,
and pelvic bones[5]; however, infrequent involvement of other bones, especially long ones might be encountered
as in the case presented here. The diagnosis is made with the help of findings related
to systemic involvement, solitary bone lesions, and after the bone biopsy.
In this report, we aimed to present a case with sarcoidosis and bone involvement and
emphasize on the importance of differential diagnosis because sarcoidosis can mimic
any granulomatous disease, primary or metastatic cancers to the bone.
Case Presentation
A 44-year-old female patient was admitted to our outpatient clinic due to complaint
of right ankle pain. The patient, who described the pain as continuous during the
day unrelated to physical activity, informed us about the past medical history of
sarcoidosis. She had applied to a health care facility due to pale and nodular lesions
present on trunk, upper and lower extremities 8 years ago ([Fig. 1]). We found out that the biopsy results of those lesions showed granulomatous dermatitis,
and that no definitive diagnosis had been made. Her radiologic work-up (X-ray, positron
emission tomography–computed tomography [PET-CT]) and lung biopsy after complaints
of shortness of breath showed sarcoidosis and she was started on appropriate therapy
5 years ago ([Fig. 2]). The patient was treated with systemic corticosteroids, methotrexate, and hydroxychloroquine
sulfate because of lung sarcoidosis.[6] Also, the patient was treated with roaccutane, topical methylprednisolone for skin
lesion. On her application to our clinic, she was found to have lytic lesions with
sclerotic points around the fibula in her ankle X-ray and further investigations were
made with the help of magnetic resonance imaging (MRI). MRI showed hypointensity and
hyperintensity lesions in T1- and T2-weighted sections, respectively ([Figs. 3]
[4]
[5]
[6]). In PET-CT evaluation, she was found to have multiple masses with hypermetabolic
activity and some lytic appearance in proximal phalange of fourth finger of left hand,
right patella, distal part of both tibia, distal part of right fibula, left talus,
bilateral calcaneal bones, and cuneiform bones of both feet, as well as fourth metatarsal
bone of right foot, first and fourth phalanges of left foot, and first and fifth phalanges
of right foot. MRI showed no soft tissue components related to these lesions. An open
biopsy was performed to the right ankle on distal end of fibula and specimens of cortical
and medullary bones were obtained. Pathological examination of tissue specimens showed
noncaseating granulomatous inflammation compatible with sarcoidosis. After biopsy,
the patient treatment continued with systemic corticosteroid and methotrexate.
Fig. 1 Erythematous nodules on arm and leg.
Fig. 2 Lung X-ray (after treatment).
Fig. 3 Hyperintense lesions in fibula and calcaneus (T2-weighted magnetic resonance imaging
section).
Fig. 4 Hyperintense lesions in calcaneus and cuneiform (T2-weighted magnetic resonance imaging
section).
Fig. 5 Hypointense lesions in calcaneus and cuneiform (T1-weighted magnetic resonance imaging
section).
Fig. 6 Hypointense lesions in fibula (T1-weighted magnetic resonance imaging section).
Discussion and Conclusion
Sarcoidosis is a disease characterized by multisystemic involvement of noncaseating
granulomas of unknown etiology. It is commonly encountered with lung, skin, and lymph
node involvements. Total 80% of cases diagnosed with sarcoidosis are females.[7] It is more common in women and young adults younger than the age of 40 years and
in African Americans and North Europeans.[8] Uveitis is the most predominant lesion in African Americans, while erythema nodosum
is the most common manifestation in North Europeans. Heart and eye involvement is
common in Japanese descendants and cardiac involvement is the most common cause of
death. In other populations, the most common cause of death is the respiratory insufficiency
due to pulmonary fibrosis. Overall mortality is between 1 and 5%.[9]
An acute form of sarcoidosis is a course defined with arthritis, erythema nodosum,
and bilateral hilar lymphadenopathy, called Löfgren's syndrome.[10] Locomotor system findings are mostly subclinical and they do not lead to a diagnosis
by themselves; however, they might cause pain as in our case.[8] Another skeletal system findings are avascular necrosis and osteoporosis secondary
to glucocorticoid use for treatment of disease.[11]
[12]
Although the etiology of sarcoidosis is not known definitely, genetic (human leukocyte
antigens) and acquired factors (air-borne antigens, viruses, fungi, and mycobacteria)
play an important role.[8]
Sarcoidosis generally involves skull, vertebrae, nasal bones, as well as bones in
hands and feet. Lytic and sclerotic lesions have been observed in cases of vertebral
sarcoidosis. Thoracic spine is the most frequently affected site in vertebral sarcoidosis.[11] Its course is asymptomatic and rarely pain may be the only manifestation. It might
also involve the joints.[11] Long bone involvement is not very common. However, in our case, multiple involvement
regions were present in addition to the bones of hands and feet. Sarcoidosis causes
dactylitis when hand bones are involved. It usually affects second and third fingers
of hands and first finger of the feet. We detected bone involvement in fourth finger
of left hand in our case. Similar to the literature, involvement of first toes of
bilateral feet were present. Differently, we did not detect any involvement of vertebrae
and skull.
Radiologically, it may manifest as cystic or osteolytic lesions or as cortical defects
and reticularizations of cortical bones as well as sclerotic and destructive lesions
or similar to periostitis.[1]
[11] Bone involvement in sarcoidosis may even cause destructive lesions resulting in
pathological fractures.[8] In MRI, T1 sequences show decreased nonspecific signal intensities, while T2 sequences
show increased nonspecific signal intensities.[11] The sensitivity of MRI may be the preferred modality for the diagnosis of osseous
sarcoidosis, especially when sacroiliitis is in the differential diagnosis.[6] CT images show bone destruction and sclerosis.
Other granulomatous diseases of the bone, such as Langerhans cell histiocytosis, tuberculosis
with bone involvement, fungal infections, viral infections such as Epstein–Barr virus
and cytomegalovirus, and Ewing sarcoma, as well as primary and secondary metastatic
bone tumors must be included in differential diagnosis.[13]
In bone biopsies, granulomas in medullary cavity and destruction in surrounding bone
tissue are characteristic.[14] Nonnecrotizing histiocytic granulomas are the elementary lesion ([Figs. 7] and [8]).
Fig. 7 Hyperintense lesions in fibula and fourth metatarsal bone (T2-weighted magnetic resonance
imaging section).
Fig. 8 Nonnecrotizing histiocytic granulomatous lesion (×200 hematoxylin and eosin stain).
There are different drug alternatives in the treatment of sarcoidosis. There are different
drug alternatives depending on the site of involvement in the body (corticosteroids,
chloroquine, methotrexate, azathioprine, leflunomide, cyclosporine, pentylphenyl,
minocycline, cyclophosphamide, anti-TNF, and rituximab).
Consequently, the definitive diagnosis should be made with biopsy followed by pathologic
investigation. The importance of other systemic examinations and anamnesis should
be emphasized to suspect of sarcoidosis. Certainly, diagnosis of sarcoidosis should
be consistent systemic finding with biopsy.
