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Interferon induced sarcoidosis with cutaneous involvement along lines of venous drainage in a former intravenous drug user

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Interferon induced sarcoidosis with cutaneous involvement along lines of venous drainage in a former intravenous drug user
Fareesa Shuja MD, Shaheen C Kavoussi MD, Mohsin R Mir MD, Reena P Jogi MD, Ted Rosen MD
Dermatology Online Journal 15 (12): 4

Department of Dermatology, Baylor College of Medicine, Houston, Texas.


Interferons are cytokines with anti-viral and anti-oncogenic properties which, in combination with ribavirin, have become the standard of care for chronic hepatitis C virus (HCV) infection by bolstering the CD4+ T-helper type 1 (Th-1) response [1]. An undesirable consequence of this is the promotion of granuloma formation via the differentiation of mononuclear cells into epithelioid cells, the activation of macrophages, and the upregulation of IL-12 production [2, 3]. Interferon-induced cutaneous granulomatous reactions are rare but have been well-described; systemic sarcoidosis presenting as a cutaneous granulomatous reaction is rarer still but does occur. Here we discuss a case of systemic sarcoidosis presenting as a delayed foreign body granulomatous reaction along lines of venous drainage in a former intravenous drug user. Only one other case of interferon-induced cutaneous sarcoidosis presenting along lines of injection drug use was found in the readily available literature [4].

Case presentation

Figure 1
Figure 1. Right forearm with firm skin-colored to reddish brown nodules along the course of the veins

A 59-year-old African-American male with HCV-related chronic active hepatitis and a remote history of injection drug use presented with a complaint of nodules developing along the superficial veins of his right forearm for several months. The patient had been receiving treatment with pegylated interferon-α-2b for the past two years. His physical examination was remarkable for scattered, non-tender, firm, reddish-brown nodules along the course of the veins of his right hand and forearm (Fig. 1).

Figure 2Figure 3
Figure 2. Skin biopsy specimen; granulomatous infiltrate involving the dermis (H&E, x100)

Figure 3. Multiple non-caseating granulomas composed of epithelioid histiocytes and giant cells (H&E, x200)

A shave biopsy was performed and histologic examination revealed granulomatous inflammation with polarizable foreign material (Figs. 2 & 3). Angiotensin-converting enzyme (ACE) level was markedly elevated at 153 U/L (reference range 3-48 U/L). A chest radiograph did not reveal any hilar lymphadenopathy, and a urine drug screen was negative.

The patient remained on interferon therapy as his hepatitis C viral load was deceasing in response to treatment. However, several months later when an esophagogastroduodenoscopy (EGD) was performed to screen for varices, biopsies of the antrum and body of the stomach revealed multiple granulomas supporting the diagnosis of systemic sarcoidosis. A gallium scan subsequently showed abnormal uptake in both lungs suggestive of parenchymal pulmonary involvement. The interferon therapy was discontinued, and the patient was referred for additional pulmonary and ophthalmologic evaluation


At least 2.7 million Americans are infected with chronic hepatitis C, and an increasing proportion of these patients are being treated with INF-α [5]. The first case of sarcoidosis in a patient receiving interferon was described by Abdi et al. in 1987 [6]. Since then, interferon-induced sarcoidosis has been detailed in numerous cases in the readily available literature [1, 4-18].

Marcoval and his group investigated cutaneous granulomatous lesions in patients with systemic sarcoidosis and found that 22 percent of the patients had foreign material present [19]. Any foreign material can initiate a foreign body immune response; for instance, scars [1, 7], hyaluronic acid injection sites [8], and tattoos [9, 10, 11, 12] have all served as a nidus for granuloma formation in patients receiving INF-α. Fischer et al. describe a patient with cutaneous sarcoidosis ten weeks after treatment with IFN-α-2a and ribavirin and ten years after injection of Artecoll, a permanent soft tissue filler containing insoluble polymethylmethacrylate [13]. The constellation of clinical and histologic findings seen in our patient suggests systemic sarcoidosis with a cutaneous foreign body granulomatous reaction to particulate foreign matter, likely talc, injected some thirty years earlier.

Remissions and reductions of cutaneous lesions have been described as being directly related to discontinuation of interferon, with 35 percent of patients requiring the addition of systemic steroids; unfortunately, the latter can increase the HCV viral load [14]. Dermatologists can play a pivotal role in identifying the early cutaneous manifestations of sarcoidosis. By discontinuing INF-α treatment, whenever feasible, we may be able to prevent the need for steroids at a later time, ultimately averting exacerbation of the initial diagnosis, hepatitis C infection.


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