A case of sarcoidosis in a patient with systemic sclerosis.

Sir,

Sarcoidosis is a multisystem granulomatous disease, including skin and lung, of unknown etiology.[1] Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by diffuse fibrosis of the skin and internal organs.[2] Co-existence of these two diseases has been reported, but is rare.[3-5] Here, we describe the case of a 68-year-old Japanese woman who developed sarcoidosis 15 years after diagnosis of limited cutaneous systemic sclerosis (lcSSc).

The patient consulted with a doctor about erythematous plaques that had appeared one year earlier on her face [Figure 1] and left knee. Fifteen years previously, at age 53, she was diagnosed with lcSSc based on proximal scleroderma from the fingers to the forearms, swelling of the fingers, Raynaud phenomenon symptoms of the hands, a positive anticentromere antibody, and an increase of collagen fiber with degenerative changes of the skin. She had taken oral tocopherol acetate for 15 years and the SSc-related skin symptoms had remitted. Laboratory data were normal at the time of consultation, including a complete blood count and tests for liver and kidney function. Serum angiotensin-converting enzyme, immunoglobulin (Ig) A, IgG, IgM, complement component 3 and 4, and total hemolytic complement (CH50) levels were also normal. Autoantibody screening was positive for antinuclear antibody (titer, 1:1280; normal range, <1:40) with a speckled pattern, and was also positive for anticentromere antibody (139; normal range, <10.0 index). Anti-topoisomerase I antibody was negative. The serum level of Krebs von den Lungen-6 was slightly elevated (580 U/ml). Chest radiography findings were normal. The lcSSc-associated pulmonary fibrosis in both lower lobes and a slight dysfunction of peristalsis of the esophagus was detected by chest computed tomography and esophagography with barium contrast medium, respectively, but did not require treatment. A gallium-67 citrate scintigram showed increased uptake in the parotid glands and a tuberculin skin test was negative. Biopsy specimens in plaques collected from the face and left knee showed multiple and well-circumscribed non-caseating epithelioid granulomas in the superficial and middle dermis [Figure 2a and b]. We diagnosed the case as sarcoidosis in a patient with lcSSc based on the findings in skin lesions, the negative tuberculin skin test, and the scintigraphic finding.

Figure 1

Erythematous plaques on the face consistent with sarcoidosis

Figure 2

A hematoxylin-eosin (HE)-stained section of specimen from the face (a) Granulomas in the dermis and a comparatively dense inflammatory cell infiltration in the superficial and middle dermis (HE, original magnification ×40) (b) A well-circumscribed non-caseating epithelioid granuloma surrounded by a comparatively large number of lymphocytes in the dermis (HE, original magnification ×200)

The prevalence of sarcoidosis and SSc is estimated to be 10.9[6] and 10.0[7] per 100,000, respectively. The mechanism underlying the coexistent occurrence is unclear. However, the reason may be the difference of immune responses closely related to sarcoidosis and SSc. Sarcoidosis is believed to be caused by Th1 immune responses.[8] In contrast, SSc is closely related to/Th2 immune responses in its early stage, but to/Th1 immune responses in its later stage.[89] In the present case, the skin sclerosis had remitted and the active lung inflammation was also not detected, and the sarcoidosis occurred 15 years after the onset of SSc, suggesting that the shift from/Th2 to/Th1 might have contributed to the development of sarcoidosis. However, the number of reported cases of coexistence of these two diseases is insufficient to establish a clear mechanism and further accumulation of data is needed.