Interstitial granulomatous dermatitis following tocilizumab, a paradoxical reaction?

Interstitial granulomatous dermatitis (IGD) is a rare dermatosis generally seen in the setting of rheumatic diseases, but also hematological disorders, internal malignances, infections, or drug induced. Herein, we report an exceptional case of an IGD with a clear chronological association with tocilizumab onset and cessation in a patient with adult-onset Still's disease. We review the granulomatous cutaneous reactions so far reported with this novel therapy: sarcoidosis, granuloma annulare, and IGD. Tocilizumab is a humanized anti-interleukin 6 receptor monoclonal antibody useful for the treatment of various systemic inflammatory disorders. Lately, it has found useful also for granulomatous diseases such as giant cell arteritis and even a promising response in IGD. Therefore, we believe our case adds the possibility of an IGD presenting as a paradoxical reaction.

Subcutaneous granuloma annulare induced by acetazolamide.

A 9-year-old boy presented with recurring subcutaneous nodules on both legs and knees temporally related each time to acetazolamide treatment for idiopathic intracranial hypertension. A biopsy of one of the lesions revealed palisaded granulomas in the hypodermis around necrobiotic collagen and interstitial accumulation of mucin, compatible with subcutaneous granuloma annulare (SGA). To the best of our knowledge, this is the first case that establishes an association between SGA and acetazolamide.

Secukinumab-associated localized granuloma annulare (SAGA): a case report and review of the literature.

Granuloma annulare (GA) is a benign, usually self-limited inflammatory skin dermatosis characterized clinically by pink-red to brown dermal papules or annular plaques. The main histologic feature is the presence of palisading or interstitial granulomas composed of necrobiotic collagen, elastic fibers, and mucin surrounded by a lymphohistiocytic infiltrate. Granuloma annulare is commonly associated with trauma, infections, diabetes mellitus, dyslipidemia, malignancy, thyroid disease, and a variety of medications. Two cases of GA have been reported in association with the use of secukinumab, a monoclonal antibody directed against interleukin 17A (IL17A), for the treatment of moderate-to-severe plaque psoriasis. We report the third case of secukinumab-associated GA in a 52-year-old woman with a history of diabetes mellitus type II, dyslipidemia, and non-alcoholic steatohepatitis. After four months of therapy with secukinumab, she presented with pink papules coalescing to plaques involving the antecubital fossae. Histology demonstrated a lymphohistiocytic palisading granuloma with central necrobiotic collagen and mucin, consistent with GA. Physicians should be aware of the possibility of GA developing in patients receiving secukinumab, especially in those with predisposing factors for GA. A better understanding of secukinumab-associated GA may lead to discoveries in GA pathogenesis and reveal broader immunomodulatory effects of secukinumab.

Granuloma annulare development in a patient with rheumatoid arthritis treated with tocilizumab: case-based review.

Granuloma annulare (GA) is the most common non-infectious disease. Despite the fact that it is a benign disease, it can be associated with a variety of disorders and certain drugs including biological disease-modifying anti-rheumatic drugs (bDMARDs). A 50-year-old man with a history of rheumatoid arthritis refractory to methotrexate, hydroxychloroquine and infliximab was treated with tocilizumab (TCZ), an interleukin-6 receptor antagonist, 162 mg subcutaneously every week. The patient responded very well to TCZ treatment with a decrease of acute phase reactants and reduction of disease activity score for 28-joints count. However, 3 months later he developed erythematous polycyclic eruptions affecting the lower extremities consistent with a diagnosis of GA which was confirmed by a skin biopsy. TCZ has been discontinued and the patient was treated with prednisone presenting complete resolution of skin manifestations after 4 weeks. This is the first case of GA development during TCZ treatment. Thus, we review the literature and discuss the relevant cases of GA development in patients treated with bDMARDs. When dealing with patients treated with these agents, all physicians should be aware of possible adverse events and the potential development of such complications.

Granuloma Annulare-Like Granulomatous Reaction to Red Tattoo Pigment.

Cutaneous reactions to tattoos can be attributed either to trauma or to the exogenous pigment introduced into the skin. Red pigment is associated with a high sensitizing potential and is the most frequently implicated pigment inducing various types of histological reactions. Herein, we describe a patient with red tattoo pigment-induced granulomatous dermatitis that histologically revealed a very rare granuloma annulare-like reaction.

[Two cases of granuloma annulare under anti-PD1 therapy]. / Deux observations de granulome annulaire sous anti-PD1.

BACKGROUND: Granuloma annulare as a granulomatous cutaneous reaction may be drug-induced. Immune checkpoint inhibitors including programmed death-1 (PD-1) inhibitors show remarkable antitumor activity and are approved for melanoma and other cancers. Different immune-related adverse effects have been described. We report herein a rare adverse effect of anti-PD1 therapy given for metastatic melanoma : granuloma annulare. PATIENTS AND METHODS: Two women receiving pembrolizumab metastatic melanoma presented with granuloma annulare. The therapy was continued in both cases. In the first patient, granuloma annulare appeared and then subsided; in the second patient, the lesion resolved completely with topical corticosteroids. DISCUSSION: While there have been reported cases of sarcoidosis induced by immunotherapies, immunotherapy-induced granuloma annulare has not been described. The pathogenesis of drug-induced granulomatous reactions is thought to involve autoimmune dysregulation affecting T cells, especially Th1 cells, which lead to granuloma formation. Granuloma annulare should thus be considered a cutaneous adverse effect of anti-PD1 immunotherapy.

Granuloma Annulare Secondary to Vemurafenib Therapy for Lung Adenocarcinoma.

Numerous cutaneous manifestations have been associated with use of BRAF inhibitors, including two previously reported cases of granuloma annulare (GA) eruptions associated with vemurafenib therapy. Both of these patients were being treated for metastatic melanoma. In this report, we describe the case of a 71-year-old man who developed classic GA lesions while being treated with vemurafenib monotherapy for nonmelanoma cancer, specifically metastatic lung adenocarcinoma positive for BRAF V600 mutation.

J Drugs Dermatol. 2017;16(10):1050-1052.

Disseminated eruptive granuloma annulare induced by levetiracetam.

Granuloma annulare (GA) is a benign, granulomatous cutaneous disease without clear etiology. Disseminated and drug induced granuloma annulare is a rare presentation. We present a 47-year-old woman with diffuse circular erythematous eruptions following treatment with levetiracetam. Her clinical and histopathological findings were compatible with the diagnosis of granuloma annulare. To the best of our knowledge, there is no previous report of this skin disease as a result of levetiracetam use. We report this case to highlight this antiepileptic drug as a possible etiologic agent in disseminated granuloma annulare.

Thalidomide-induced granuloma annulare.

Granuloma annulare (GA) is an acquired, usually self-limiting, asymptomatic granulomatous skin disease with well recognized clinical and histological features that occurs in children and adults generally before the age of 30. Five clinical types are described including the localized, generalized, subcutaneous, perforating, and patch forms. The possible role of immune dysregulation has been pointed out in the pathogenesis of GA, as it has been reported in association with several diseases and conditions like diabetes, thyroid diseases, malignancies, tuberculosis, human immunodeficiency, Epstein Barr and hepatitis C virus infection. Drug-induced GA is a rare presentation, that can appear similar or identical to idiopathic GA. We present a 75-year-old Caucasian man with a violaceous ring-like firm, papular eruption, localized on the dorsal aspect of both hands, with histological features of GA, which subsequently resolved with the discontinuation of thalidomide he had started 1 month earlier for the treatment of a multiple myeloma. The lesions appeared with renewed intensity after resuming a therapy cycle. Jones's algorithm for the diagnosis of adverse drug reactions (ADR) showed a certain association, thus the final diagnosis of thalidomide-induced GA was made.

Hepatitis C virus treatment with pegylated interferon-alfa therapy leading to generalized interstitial granuloma annulare and review of the literature.

We discuss the diagnosis and management of a case of generalized granuloma annulare (GA) occurring in a 49-year-old man when being treated with pegylated interferon-alfa for hepatitis C infection. In our case, the GA lesions remained despite an undetectable hepatitis C viral load. The GA resolved only with treatment cessation.

Perforating granulomatous dermatitis reaction to exogenous tattoo pigment: a case report and review of the literature.

: The majority of cutaneous hypersensitivity reactions to exogenous tattoo pigments can be histologically classified as lichenoid or granulomatous. The etiology is still uncertain but is generally accepted to be a delayed-type hypersensitivity reaction to either the pigment itself or its carrier solution. In this report, we review the literature concerning adverse reactions to tattoos. In addition, we describe the second case of a localized granulomatous dermatitis to the red dye within a tattoo that histologically resembled granuloma annulare. This is the first reported example of a perforating granuloma annulare-like reaction.

Granuloma annulare-like reaction to the bacillus Calmette-Guerin vaccination.

We report the case of a 6-month-old girl with a granuloma annulare (GA)-like reaction to the bacillus Calmette-Guerin (BCG) vaccination. The eruption developed at the vaccination site 1 month after vaccination and the lesion gradually disseminated over the body within 2 months. A biopsy specimen of the skin lesion showed degenerated collagen bundles surrounded by imperfect palisading histiocytes, lymphocytes and epithelioid cells in the dermis, which led to a diagnosis of GA-like reaction as a secondary reaction to BCG inoculation. The eruption at the vaccination site and the scattered GA reaction resolved after 1 month of treatment with prednisolone valerate acetate ointment, leaving only pigmentation.

Granuloma annulare photoinduced by paroxetine.

Granuloma annulare (GA) is a benign granulomatous skin disease with several clinical manifestations and characteristic histological findings. GA located in photoexposed areas is a rare finding and its association to a drug-induced systemic photosensitivity is even less common. To the best of our knowledge, only one case of systemic drug photosensitivity manifesting as a GA has been reported. We describe a patient with systemic photosensitivity to paroxetine with clinical and histological manifestations of GA, which was confirmed by the photobiological study. The phototest revealed a reduction of the minimal erythematous dose for UVB while taking the paroxetine and its normalization after its withdrawal, which was accompanied by the clinical resolution of the skin eruption. The manifestation of systemic drug photosensitivity as a GA like in our case is exceptional.

Nivolumab-Induced Granuloma Annulare.

Immune-checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab have transformed oncologic therapeutic modalities. By disrupting tumor-induced immunosuppression, ICIs have facilitated effective treatment of numerous malignancies, including metastatic melanoma; however, due to the ensuing disturbance of the immune system, various immune-mediated adverse reactions have been reported with ICI therapy. We present a case of nivolumab-induced granuloma annulare in a 54-year-old woman. Recognition of the association between ICI therapy and cutaneous adverse reactions is crucial to ensure accurate diagnosis and adequate treatment of such reactions in patients taking ICIs.

Unusual palisading and necrotizing granulomas associated with a lubricating agent used in lipoplasty.

Palisading granulomas with necrobiosis are frequently encountered in dermatopathology, with granuloma annulare, necrobiosis lipoidica diabeticorum, and rheumatoid nodule being the most frequently rendered diagnoses. We report a series of 9 patients who developed palisading, necrobiotic, and necrotizing granulomas, associated with the presence of foreign material introduced through the use of a lubricating agent containing a copolymer (Carbopol 934) for liposuction. The patients ranged in age from 29 to 54 years old and presented with multiple, disfiguring, and nonhealing wounds at sites where lipoplasty had been performed. All specimens showed similar histologic findings, with the formation of palisading granulomas around extensive areas of necrobiosis with foci of true necrosis. Spaces containing minute fragments of crystalloid-appearing foreign material, birefringent with polarized light, were also identified. Special stains including acid fast, Gram, Giemsa, and/or periodic acid-Schiff were negative for organisms in all cases, as were cultures performed in 5 cases. Given the presence of foreign material and true necrosis, these findings were inconsistent with granuloma annulare, necrobiosis lipoidica diabeticorum, or rheumatoid nodule and were interpreted as a unique reaction to the foreign material. Therefore, this seems to be a distinct reaction pattern that has not been previously reported in the literature and may be important to include in the differential diagnosis in patients with necrotizing granulomatous disease.