Pulmonary and cutaneous sarcoidosis associated with interferon therapy for melanoma

Interferon alfa is widely used as adjuvant therapy for melanoma. Numerous side effects have been attributed to interferon alfa. Interferon alfa-induced sarcoidosis is an uncommon event. We report the third case of pulmonary and cutaneous sarcoidosis in the course of interferon alfa treatment for melanoma. Most cases of sarcoidosis have been reported during treatment of chronic hepatitis C. The prognosis is good with discontinuation of treatment. Other than interferon therapy, sarcoidosis or granulomatosis reactions rarely have been reported in malignant melanoma. We discuss and review the literature on the physiopathology of sarcoidosis brought on by interferon therapy.     

Systemic sarcoidosis and cutaneous lymphoma: is the association fortuitous?

The association of systemic sarcoidosis and malignant lymphoma is known as the 'sarcoidosis-lymphoma syndrome'. Cutaneous involvement is rare in this syndrome. We report a 52-year-old woman who was diagnosed as having tumour-stage mycosis fungoides. Complete remission was achieved by combination therapy consisting of isotretinoin, interferon (IFN) alpha, electron beam irradiation, photochemotherapy and topical corticosteroids. Three years later, the patient developed systemic sarcoidosis characterized by yellowish papules on the abdominal wall and the eyelids that histologically revealed non-caseating granulomas, multiple fine-nodular interstitial pulmonary infiltrates on chest X-ray, hilar lymphadenopathy, decreased vital capacity and increased lymphocyte count in bronchoalveloar lavage fluid. As opposed to most of the reported cases, in our patient the manifestation of cutaneous lymphoma preceded the diagnosis of systemic sarcoidosis. We review the cases reported in the literature and discuss a possible causal and temporal relationship as well as the role of IFN alpha in the development of sarcoidosis.     

Sarcoidosis associated with pegylated interferon alfa and ribavirin treatment for chronic hepatitis C: a case report and review of the literature

BACKGROUND: At least 2.7 million Americans are infected with chronic hepatitis C. An increasing number are treated with interferon alfa plus ribavirin regimens. Not surprisingly, this immune stimulation is associated with the development of autoimmune and cutaneous diseases. Several cases of sarcoidosis have been reported with hepatitis C treatment, most recently in association with pegylated interferon alfa plus ribavirin. Systemic manifestations of sarcoidosis are usually treated with oral steroids, which unfortunately often increase the hepatitis C viral load. Thus, it is important to ascertain whether systemic corticosteroids are required to treat interferon alfa-associated sarcoidosis. OBSERVATIONS: We report the third case of cutaneous sarcoidosis in association with pegylated interferon alfa plus ribavirin treatment. Our patient had both cutaneous and pulmonary involvement, which has been spontaneously resolving since his treatment regimen was completed. In addition, we review the 12 previously reported cases of cutaneous sarcoidosis that occurred in patients undergoing hepatitis C treatment with interferon alfa. CONCLUSIONS: As the number of patients being treated with interferon alfa and ribavirin for hepatitis C increases, it is essential that dermatologists recognize the association of this treatment with sarcoidosis, because skin lesions may provide the first clue to diagnosis. Development of sarcoidosis may relate to hepatitis C as a possible antigenic trigger in the presence of an enhanced helper T cells type 1 response from treatment. Sarcoidosis with skin lesions in patients undergoing hepatitis C treatment often follows a benign course, and interferon alfa therapy may sometimes be continued with resolution of sarcoidosis occurring spontaneously or within a few months of completing treatment. Cautious use of systemic corticosteroids is warranted given their adverse effects on hepatitis C viral loads.     

Alpha-interferon induced sarcoidosis mimicking metastatic melanoma

Despite its modest potential benefit, alpha-interferon is one of the most frequently employed therapies for melanoma. With the increasing incidence of melanoma, a parallel increase in interferon use and the associated adverse reactions that accompany interferon therapy should be expected. We present a case of an interferon-induced sarcoidosis-like reaction in a melanoma patient that was initially misinterpreted clinically and radiographically as metastatic melanoma. The etiology of sarcoidosis remains a mystery, but appears to involve Th-1 cytokines such as interferon and interleukin-2. Observance of a sarcoidosis-like reaction induced by interferon therapy lends additional support to the importance of this cytokine in the pathogenesis of sarcoidosis. It is important for pathologists to be aware of this entity when interpreting biopsies from melanoma patients treated with interferon.     

Cutaneous sarcoidosis during interferon alfa and ribavirin treatment of hepatitis C virus infection: two cases

Interferon-induced sarcoidosis is well documented. We report two new cases of sarcoidosis in two patients with hepatitis C virus infection treated with interferon alfa and ribavirin. These patients developed cutaneous sarcoidosis about 3 months after the beginning of the combination therapy. Spontaneous regression of the lesions was noted after discontinuation of the treatment. There have been more than 20 observations of the appearance or aggravation of this granulomatosis with interferon alfa and more recently with the combination of interferon alfa plus ribavirin. Dermatological signs are found in 50% of cases, and are often diagnostic. Other clinical symptoms of sarcoidosis resemble side-effects of interferon. The evolution is fairly stereotypical and is marked by a regression of the lesions following a dose reduction or curtailment of interferon. Interferon alfa acts by stimulating the T-helper (Th) 1 immune response. In addition to its antiviral action, ribavirin also enhances the Th1 response. Indeed, the superiority of the combination of interferon alfa and ribavirin in terms of antiviral action is corroborated by the enhancement of a Th1-type immune reaction by this combination. At the same time, this immune cell reaction triggers a greater granulomatous reaction.     

Interferon-alpha Induced Sarcoidosis with Cutaneous Involvement along the Lines of Venous Drainage

Sarcoidosis is a systemic inflammatory disease of an unknown origin and it is characterized by the presence of noncaseating epitheloid cell granulomas in multiple organs. Herein we report on a case of cutaneous and pulmonary sarcoidosis that was associated with interferon alpha treatment for hepatitis C. A 39-year-old man, a former intravenous drug user, presented with several erythematous papules on both antecubital areas. The histopathologic finding of a skin biopsy showed noncaseating granuloma. The mediastinal and axillary lymph nodes were enlarged on chest X-ray and computed tomography. To the best of our knowledge, this is the first report of cutaneous and pulmonary sarcoidosis that was associated with interferon treatment in the Korean dermatologic literature.     

Development of cutaneous sarcoidosis in a patient with chronic hepatitis C treated with interferon alpha 2b

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology that most commonly affects young adults. A probable induction of sarcoidosis by interferons (IFN) has been published. To this date, few cases of cutaneous sarcoidosis inpatients with chronic hepatitis C under interferon treatment have been reported. OBJECTIVE: We describe a 50-year-old woman with chronic hepatitis C who developed lesions of cutaneous sarcoidosis three months after IFN treatment. CONCLUSIONS: The possible role of INF therapy in the development of cutaneous sarcoidosis in a patient with chronic hepatitis C should be considered.     

Cutaneous sarcoidosis and infliximab: evidence for efficacy in refractory disease

Biological therapy with tumour necrosis factor alpha antibodies continues to offer a life‐changing option for a range of autoimmune and inflammatory skin conditions. We present three cases of sarcoidosis, with refractory cutaneous disease successfully treated with infliximab. A review of the literature shows increased numbers of cases of refractory cutaneous sarcoidosis successfully cleared with infliximab therapy.     

TNF‐α: a treatment target or cause of sarcoidosis?

Sarcoidosis is a systemic granulomatous disease that affects numerous organs, commonly manifesting at the lungs and skin. While corticosteroids remain the first line of treatment, tumour necrosis factor alpha (TNF‐α) inhibitors have been investigated as one potential steroid sparing treatment for sarcoidosis. TNF‐α is one of many components involved in the formation of granulomas in sarcoidosis. While there have been larger scale studies of biologic TNF‐α inhibition in systemic sarcoidosis, studies in cutaneous disease are limited. Paradoxically, in some patients treated with biologic TNF‐α inhibitors for other diseases, treatment can induce the development of sarcoidosis. In the light of this complexity, we discuss the role of TNF‐α in granuloma formation, the therapeutic role of TNF‐α inhibition and immunologic abnormalities following treatment with these TNF‐α inhibitors including drug‐specific alterations involving interferon‐γ, lymphotoxin‐α, TNF receptor 2 (TNFR2) and T‐regulatory cells.     

Postoperative interferon hydrogel treatment. A method for the successful therapy of chronic persistent giant condylomas in an immunologically deficient patient with Hodgkin's disease

The local application of recombinant interferon alpha 2c hydrogel (1.10(6) I.U. recombinant interferon alpha 2c/g hydrogel) given as an adjuvant therapy after electrosurgery led to a complete cure, without relapse, of previously recalcitrant giant condylomata acuminata similar in appearance to Buschke-L?wenstein's tumors in a 19-year-old female patient suffering from Hodgkin's disease (stage II/III). Recombinant interferon alpha 2c hydrogel given as an adjuvant therapy to surgery may have more antiviral and antiproliferative effects than immunomodulating activities. This combined topical application form of interferon alpha is a safe and effective treatment, which is recommended especially in immunocompromised individuals suffering from genital HPV infection unresponsive to systemic interferon treatment or conventional therapy modalities.     

Cutaneous lesions as initial signs of interferon α-induced sarcoidosis: report of three new cases and review of the literature

Sarcoid reactions are well-recognized adverse events during interferon (IFN) therapy. They are frequently underdiagnosed because misinterpreted as IFN-induced side effects. Sarcoid cutaneous lesions may therefore represent useful hints to an early diagnosis, but their incidence is unknown. We report three new cases of mono-localized, purely cutaneous IFNα-induced sarcoidosis. In addition, an extensive review of the literature, with special attention to skin involvement, was performed through a PubMed search. The analysis of the retrieved articles showed that cutaneous lesions are frequent signs of IFN-induced sarcoidosis. Skin involvement is documented in 56% of the reports and it appears among the presenting and diagnostic signs of a sarcoid reaction in 51%. Special attention to dermatologic signs is imperative in the course of IFN therapy because even minimal skin involvement may offer a clue to an early diagnosis of IFN-induced sarcoidosis.     

Cutaneous sarcoidosis developing after treatment with pegylated interferon and ribavirin: a new case and review of the literature

Sarcoidosis is a multisystem granulomatous disease that affects multiple organs in adults between 20 and 50 years old. Interferon alpha (IFN-α) is an immunomodulator that has been used in a wide range of diseases, including hepatitis C virus infection, multiple sclerosis, and other types of neoplasias, including leukemia, lymphoma, Kaposi's sarcoma, and melanoma. Standard IFN-α-induced sarcoidosis has been reported, but there are few reports of cutaneous sarcoidosis with pegylated IFN-α therapy. We present a new case of cutaneous sarcoidosis after treatment with pegylated IFN, and a review of the literature.     

Livedo reticularis associated with interferon α therapy in two melanoma patients

We report two patients who developed intense livedo reticularis clearly related to the administration of interferon alpha 2b as an adjuvant therapy for melanoma. Histological studies showed scattered perivascular infiltrates without vasculitis. Laboratory tests excluded any underlying condition. Resolution of the symptoms was observed in both patients when interferon alpha was withdrawn. These cases highlight the occurrence of livedo reticularis as an uncommon side-effect of interferon alpha treatment.     

Development of cutaneous sarcoidosis during treatment with tumour necrosis alpha factor antagonists

The use of tumour necrosis factor alpha (TNF‐α) antagonists is increasing in the field of dermatology. These agents have been used for multiple inflammatory and immune skin conditions, but most notably, psoriasis. Adverse effects of anti‐TNF‐α agents have been reported, including the paradoxical development of sarcoidosis. We present an unusual case of limited cutaneous sarcoidosis developing while the patient was on etanercept therapy, and a review of the current literature.     

Ulcerative sarcoidosis in the legs with granulomatous vasculitis

We present a case of a patient with pulmonary sarcoidosis who developed ulcerative sarcoidosis with granulomatous vasculitis on the lower legs. Ulceration is a rare presentation for sarcoidosis and this case gives further evidence that an underlying vasculitis may be an aetiological factor. Granulomatous vasculitis, classically associated with Wegener's granulomatosis, lymphomatoid granulomatosis, or Churg-Strauss syndrome, is also commonly described in pulmonary sarcoidosis. It has, however, only rarely been described in cutaneous sarcoidosis. Our patient's leg ulcers have responded well to immunosuppressive therapy with tapered corticosteroid and low-dose azathioprine.     

Cutaneous ulceration after injection of polyethylene-glycol-modified interferon alpha associated with visual disturbances in a melanoma patient

Interferons are used in the therapy of multiple sclerosis, Kaposi's sarcoma, hepatitis and melanoma. Their short half-life that requires frequent injections can be increased by polyethylene glycol (PEG) modification. A 50-year-old patient was diagnosed as having an acrolentiginous melanoma (Breslow >5 mm, Clark level IV) and inguinal lymph node metastases. After surgical excision and lymphadenectomy, immune therapy with 6.0 microg pegylated interferon alpha(2b)/kg body weight, s.c., was started. Cutaneous ulcerations at the injection sites developed 9 months after treatment initiation. The patient also developed blurred vision and presented with binasal scotomas and pathological visually evoked potentials and electroretinogram. The cutaneous ulcerations slowly healed under local therapy and reduction of the concentration of the PEG-modified interferon from 0.86 to 0.43 mg/ml. The dosage was maintained. Two months later, the therapy was stopped due to disease progression. Vision subsequently recovered. Cutaneous reactions evolved at the sites of subcutaneous injections of PEG-modified interferon alpha(2b). Changes in vision can probably be attributed to immunotherapy.     

Angiosarcoma of the scalp and face: failure of an interferon alpha treatment

Angiosarcoma of the scalp and face is a rare malignant endothelial tumor arising in elderly people. Treatment is disappointing and prognosis remains poor. We report two cases of angiosarcoma of the scalp and face relapsing after classical therapy with surgery and radiotherapy and treated with interferon alpha. The tolerance was poor and the disease progressed 2 and 5 months after the onset of the treatment. When used alone, interferon alpha does not appear as an effective treatment in this kind of angiosarcoma.     

Sarcoidosis with extensive cutaneous ulceration. Unusual clinical presentation

A 70-year-old white woman with sarcoidosis and insulin-resistant diabetes mellitus presented with extensive cutaneous ulcerations. Both the cutaneous lesions and the systemic features of sarcoidosis showed a dramatic improvement during oral corticosteroid therapy. When extensive cutaneous ulcerations are present, it is important to consider sarcoidosis, as these may be the only presenting sign of the disease. Unlike ulcerated necrobiosis lipoidica diabeticorum, sarcoidal ulcerations may respond well to treatment with oral corticosteroids.     

TREATMENT OF BASAL CELL CARCINOMA WITH INTRALESIONAL INTERFERON ALPHA: A CASE REPORT AND LITERATURE REVIEW

We report the case of a 76 year old man with three ulcerated basal cell carcinomas on his lower limbs. He was considered unsuitable for surgical therapy and was treated by intralesional interferon alpha-2b (Intron A) injections. Twenty months post therapy two of the three treatment sites remain clinically cured. Recurrence occurred at the site which received the smallest total dose of interferon. A review of the therapeutic trials of interferon alpha for basal cell carcinoma is presented. We conclude that interferon alpha-2b is a useful agent for treatment of basal cell carcinoma in selected patients.