Lesions Of Granuloma Annulare Research Articles

Association between adipophilin expression and risk of dyslipidaemia in patients with granuloma annulare

BackgroundAn association between granuloma annulare (GA) and dyslipidaemia has been reported. Adipophilin expression may play a plausible role as a cutaneous biomarker for dyslipidaemia in patients with GA; however, this potential link remains to be explored. MethodsPatients with GA were identified at our hospital between January 1, 1990, and December 31, 2021, with a thorough review of their clinical and histological characteristics. Adipophilin staining was assessed in biopsies of GA lesions. ResultsA total of 107 patients with GA were included. The prevalence of dyslipidaemia in patients with positive adipophilin staining was clearly higher than in those with negative labelling (62.3% vs 13.3%). Relative to the dyslipidaemia risk for patients with negative adipophilin expression, the odds for patients with positive adipophilin expression were increased 10-fold (OR: 10.8; p-value<.01). We identified 23 incident cases of dyslipidaemia over a median follow-up period of 91 months among 54 patients with no history of dyslipidaemia. The patients with positive adipophilin expression showed a higher risk of developing dyslipidaemia (HR: 8.9; p-value<.01). ConclusionsPatients with positive adipophilin staining in their GA biopsies were found to be associated with a higher risk for both baseline and incident dyslipidaemia.

Granuloma Annulare: A Rare and Unusual Lesion of the Eyelid.

Granuloma annulare (GA) is common in children, but the eyelids are not a common site of involvement. Due to the infrequent association of eyelid lesions with GA, patients are unable to receive early and effective treatment. Our eleven-year-old female patient presented with the complaint of a painless mass on the right upper eyelid that did not respond to the topical drugs prescribed in clinics. An incisional biopsy was performed to diagnose the patient with an unusual subcutaneous raised lesion on the eyelid. The histopathological result was consistent with immunohistochemical staining and granuloma annulare showing CD68 positivity. Intralesional steroid injection was performed because the lesion caused the patient cosmetic problems. The lesion began to regress significantly in the first week and did not recur. The atypical location of the GA lesions in the eyelid seen at a young age should be kept in mind and treated effectively.

Immunohistochemical Features of MMP-9 and pSTAT1 in Granuloma Annulare and Sarcoidosis: A Comparative Study of 62 Cases.

Granuloma annulare (GA) and sarcoidosis are granulomatous inflammatory diseases that share similarities. To identify the histological and immunohistochemical (IHC) features of GA and sarcoidosis. A retrospective review of 36 patients with GA and 26 with sarcoidosis was performed. Results from hematoxylin and eosin (H&E) staining and IHC staining of MMP-9 and pSTAT1 within the skin lesions of GA and sarcoidosis were analyzed, and random forest was applied for developing a predictive model. Significantly greater expressions of MMP-9 (especially in elastic fibers, EFs, P < 0.0001) and pSTAT1 (P = 0.0003) were observed in lesion samples of GA versus sarcoidosis patients. In GA patients, MMP-9 was significantly upregulated in the interstitial type (P = 0.0222), while staining of pSTAT1 was positively correlated with the area of mucinous collagen in palisading GA (R = 0.5356, P = 0.0484). In sarcoidosis patients, MMP-9 (R = -0.7127, P = 0.0009) and pSTAT1 (R = -0.5604, P = 0.0067) were found to show stronger expressions in lesions with less lymphocyte infiltration. The predictive model demonstrated an AUC of 0.9675. These results indicate that MMP-9 and pSTAT1 might exert roles in granulomatous inflammation in different modes, and the presence of more robust MMP-9 staining in EFs appears to be more suggestive of GA.

Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib

Granuloma annulare (GA) is a common cutaneous inflammatory disorder characterized by macrophage accumulation and activation in skin. Its pathogenesis is poorly understood, and there are no effective treatments. The potential health implications of severe GA are unknown. We sought to better understand GA pathogenesis and evaluate a molecularly targeted treatment approach for this disease. We used single-cell RNA sequencing to study the immunopathogenesis of GA and also evaluated the efficacy of tofacitinib (a Janus kinase 1/3 inhibitor) in 5 patients with severe, long-standing GA in an open-label clinical trial. Using single-cell RNA sequencing, we found that in GA lesions IFN-γ production by CD4+ T cells is upregulated and is associated with inflammatory polarization of macrophages and fibroblasts. In particular, macrophages upregulate oncostatin M, an IL-6 family cytokine, which appears to act on fibroblasts to alter extracellular matrix production, a hallmark of GA. IL-15 and IL-21 production appears to feed back on CD4+ T cells to sustain inflammation. Treatment of 5 patients with recalcitrant GA with tofacitinib inhibited IFN-γ and oncostatin M, as well as IL-15 and IL-21, activity and resulted in clinical and histologic disease remission in 3 patients and marked improvement in the other 2. Inhibition of these effects at the molecular level paralleled the clinical improvement. Evidence of systemic inflammation is also present in some patients with severe GA and is mitigated by tofacitinib. The Janus kinase-signal transducer and activator of transcription pathway is activated in GA, likely in part through the activity of IFN-γ and oncostatin M, and Janus kinase inhibitors appear to be an effective treatment.

A case of granuloma annulare mimicking tinea cruris

Granuloma annulare (GA) is a benign, self-limited skin disease of unknown etiology characterized by annular, flesh-colored to erythematous grouped papules or plaques. Lesions of GA are typically located on the lateral or dorsal surfaces of the hands and feet, arms, thighs, and trunk. We present the case of a patient with GA who presented with erythematous, annular plaques localized to the bilateral inguinal folds, mimicking tinea cruris. On clinical examination, the lesions were thought to be tinea cruris. A subsequent punch biopsy revealed the lesions to be granuloma annulare. This case highlights an unusual location where GA can first present in a patient. It also suggests that GA should be considered among the differential diagnoses along with tinea cruris, when evaluating localized annular lesions of the groin.

Granuloma annulare: relationship to diabetes mellitus, thyroid disorders and tuberculin skin test

BackgroundGranuloma annulare is a benign inflammatory disease of the skin. The etiology and pathogenesis of the disease are not yet determined, but some authors have proposed that it might be associated with a variety of underlying conditions such as thyroid disorders, diabetes mellitus and positive tuberculin skin test.ObjectiveThis study was conducted to find the probable relationship between granuloma annulare and diabetes mellitus, thyroid disorders and positive tuberculin skin test.Patients and methodsA total of 28 patients with granuloma annulare were recruited from our dermatology outpatient clinic, and data on sex, age and distribution of granuloma annulare lesions were collected. Forty-one age- and sex-matched apparently healthy volunteers serving as controls were also included. Thyroid stimulating hormone (TSH), fasting blood sugar (FBS) and tuberculin skin tests were performed for both groups.ResultsMean serum level of FBS in the patient group was significantly higher than the mean serum level of FBS in the control group (110.60±46.31 mg/dL versus 88.39±10.58 mg/dL, respectively, p=0.004). Mean serum level of TSH in the patient group was 3.43±2.73 mIU/L, which was not significantly different from the mean serum level of TSH in the control group (3.26±2.11 mIU/L, p=0.772). Four individuals in the patient group and only 1 in the control group had a positive tuberculin skin test.ConclusionGranuloma annulare patients are better to be assessed for diabetes mellitus, but the relationship between this skin disease and thyroid disorders or tuberculin skin test still needs to be investigated.

A Case of Acute-Onset, Painful Acral Granuloma Annulare.

Dear Editor: Acute-onset, painful acral granuloma annulare (GA), a rare variant first described by Brey et al.1 in 2006, is characterized by sudden onset of painful lesions on the hands and feet, and scattered lesions at other sites. Patients may have associated arthralgia, diarrhea, and fever. The erythrocyte sedimentation rate (ESR) may be elevated1. A 57-year-old woman presented with painful lesions on the hands and legs 4 months ago. The lesions abruptly began as small erythematous plaques and slightly enlarged after beginning. The patient experienced febrile sensations, myalgia, and back pain a month before developing the lesions. Intermittent treatment of oral prednisolone from a local clinic alleviated her back pain, but new cutaneous lesions persistently develop. Physical examination revealed tender, erythematous, annular plaques on the palms, lateral sides of the fingers, and the legs (Fig. 1). Initial laboratory examination by a rheumatologist revealed an elevated ESR of 52 with otherwise unremarkable findings for rheumatoid factor, anti-neutrophilic cytoplasmic antibody, anti-cardiolipin antibody and thyroid function test. Biopsy specimen from the left second finger revealed a palisade of histiocytes surrounding degenerated collagen and mucin in the dermis (Fig. 2A, B). Alcian blue (pH 2.5) staining highlighted mucin in the center of the granuloma (Fig. 2C). Based on the clinical and histological findings, acute-onset, painful acral GA was diagnosed. Fig. 1 Tender erythematous annular plaques on the lateral side of second and third finger. Fig. 2 (A) Palisade of histiocytes surrounding degenerated collagen and mucin in the dermis. A broad zone of mucinous degenerated collagen fibers with infiltrating lymphohistiocytic granuloma (H&E, ×100). (B) (H&E, ×400). (C) ... Although the occurrence of GA on the dorsum of the hands is frequent, the involvement of the palms appears to be very rare2,3,4,5. Generally, GA is characterized by asymptomatic or mildly pruritic lesions, but GA on the palms manifests variable clinical presentations, including painful or pruritic papules and plaques2,3,4. Acute-onset, painful acral GA also manifests unusual painful lesions similar to GA lesions on the palms. However, the former shows constitutional symptoms in addition to skin lesions, which may raise suspicion about an autoimmune disease. Therefore, unnecessary examinations and treatments may be performed and final diagnosis may be delayed. Brey et al.1 reported 2 of 4 patients presenting with arthralgia, which increased authors' concern that the disease might represent an early manifestation of an autoimmune disease. However, extensive serologic and radiologic examinations for autoimmune diseases were negative. Our patient was initially also evaluated by a rheumatologist, but all serologic findings for autoimmune diseases were unremarkable except for an elevated ESR. From this clinical viewpoint, we assume that acute-onset, painful acral GA could be classified as a distinct variant of GA distinguishing it from GA on the palms. Acute-onset painful acral GA should be differentiated from conditions including Sweet's syndrome, interstitial granulomatous dermatitis with arthritis, palisaded neutrophilic and granulomatous dermatitis, and rheumatoid nodule, which may present similar clinical presentations like painful papules or plaques and constitutional symptoms1. Herein, we report a very rare and interesting case of acute-onset, painful acral GA. Clinicians should be aware of the atypical clinical presentation of GA such as painful and/or tender acral eruptions with constitutional symptoms. To classify acute-onset, painful acral GA as a variant of GA, more reports of cases are needed.

Granuloma annulare and necrobiosis lipoidica with sequential occurrence in a patient: report and review of literature.

Granuloma annulare (GA) and necrobiosis lipoidica (NL) are granulomatous diseases of undetermined etiology. Rarely, both dermatoses have been reported to occur concomitantly in patients. GA and NL are characterized histologically by areas of necrobiosis of collagen. The two diseases share some common characteristics, which may suggest that these dermatoses could occur as a spectrum in some patients or possibly share a similar pathogenesis. We report on a 67-year-old Caucasian woman with a history of NL on the anterior shins that later developed lesions of GA on the breasts, trunk, and wrist. We also review the literature and discuss the characteristics of patients with concomitant GA and NL.

Triple antibiotic combination therapy may improve but not resolve granuloma annulare.

Granuloma annulare is a fairly common entity yet lacks reliable treatment options especially when multiple lesions or dissemination exists. A recent case series suggests that a regimen of three oral antibiotics may prove to be an effective treatment. Our objective is to evaluate the efficacy of once monthly triple antibiotic therapy for granuloma annulare. We conducted an open-label prospective study of subjects with at least five lesions of granuloma annulare who received once monthly rifampin, ofloxacin, and minocycline for 6 months. Improvement was measured with a novel objective Granuloma Annulare Severity Index (GASI) scoring system. Twenty-one subjects enrolled. Ten subjects (48%) achieved at least a 50% reduction in their GASI, including three subjects (14%) who reached 75% improvement and one subject (5%) whose skin cleared. Six subjects (29%) had no change or worsening of their granuloma annulare. Median GASI scores decreased significantly by 15 points (p < 0.01), although the clinical significance of this result is unclear. As this was a small open-label study without a control group, we cannot determine if the results simply reflect the natural course of the disease. The GASI is not a validated assessment tool. Once monthly triple antibiotic use may improve but not clear granuloma annulare over 6 months. Randomized trials may be warranted to further assess this therapy.

Unusal presentation of granuloma annulare restricted over the palms: a rare case presentation

We report a patient with erythematous firm papules and nodules over palms. Histological examination, which identified epidermis showed marked hyperkeratosis and dermis with perivascular lympho-histiocytic infiltrate which also extended in between the collagen bundles with occasional multinucleated giant cells and mucin deposition. This established the diagnosis of Granuloma Annulare (GA). This is an unusual presentation because of the late onset, uncommon localization, and absence of classical lesions of GA elsewhere.

Periocular Granuloma Annulare: A Case Report and Review of Literature

Granuloma annulare (GA) is a granulomatous dermatosis that rarely presents on the face and is extremely uncommon in the periocular region. We report our experience with the presentation and management of GA lesions on the eyelids of a 17-year-old girl. We performed a review of published literature and identified 13 cases of pediatric periocular GA. One additional case was identified upon review of all pediatric GA cases at the Cleveland Clinic Foundation. Review of these cases suggests that periocular GA is a benign condition that spontaneously regresses within a few months. GA nodules have a predilection for the upper eyelids. A greater incidence is noted in African American children. Awareness of the self-resolving nature of this condition can prevent unnecessary surgical excisions in affected children.

Does infection play a role in the pathogenesis of granuloma annulare?

Does infection play a role in the pathogenesis of granuloma annulare?

Granuloma annulare on the palms: A clinicopathological study of seven cases

Granuloma annulare (GA), a common dermatological condition of unknown etiology, affecting all ages. Involvement of the palms appears rare, posing a diagnostic challenge. This study was conducted to document various clinical and histopathological features of GA on the palms. To study clinical and histopathological variations in granuloma annulare on palms. A total 7 patients from our outpatient department with lesions of GA, exclusively on the palms, were studied over a period of 6 months from March 2011 to August 2011. Total of 8 biopsies were studied. In each patient, diagnosis was made on clinico-pathological correlation. Various clinical and histopathological features were analyzed. An average age of onset was 47 years, male: female ratio was 1.33: 1, and average disease duration was 9 months. Pain was the most common symptom. Clinically, the most common presentation was pseudovesicles. Histologically, both classic palisading and interstitial pattern were seen. Perineural granulomas, perieccrine granulomas, elastophagocytosis were seen additionally. In 5 out of 7 patients, diagnosis was missed clinically. GA on palms poses a diagnostic challenge due to variable presentations. Histopathology is of vital importance for correct diagnosis and treatment. GA should be considered in differential diagnosis of papular lesions on palms.

Treatment of granuloma annulare with the 595‐nm pulsed dye laser, a multicentre retrospective study with long‐term follow‐up

Granuloma annulare (GA) is limited in most cases to isolated lesions, but more widespread generalized forms can be observed. In both cases, the treatment remains highly challenging. Isolated case reports suggested the interest of treating GA with a pulsed dye laser (PDL). To evaluate the PDL in treating GA. Retrospective multicentre study. Each patient should have at least two lesions of GA including at least one that remained untreated to serve as a control. The evaluation was performed on an Investigator Global Assessment for each lesion as compared with baseline. Thirteen patients (five with localized GA and eight with generalized GA) with a total of 59 lesions have been treated with a maximum of three PDL sessions. Sixteen lesions (27.1%) achieved >50% of clearing (14% of lesions for generalized GA and 56.2% for localized GA). Transient hyperpigmentation and crusting were observed in 59% and 86% of lesions respectively. The median follow-up was 6 months (2-12) and 10 lesions (all in generalized GA) recurred after initial clearing. Generalized GA showed weak improvement after treatment with a high recurrence rate. Only localized forms showed notable improvement in a more than half of treated lesions. Thus, PDL could be proposed as an alternative approach, but only for localized forms of GA.

Multiple lesions of granuloma annulare on the hand in a patient with scabies

Granuloma annulare induced by scabies infection has been described previously in three patients. In this report, we share our observation of a fourth case.

Anti-Tumor Necrosis Factor-α Treatment with Infliximab for Disseminated Granuloma Annulare

Granuloma annulare (GA) is a chronic inflammatory disease of unknown etiology characterized by the development of plaques preferentially localized to the distal extremities. Spontaneous remission and relapses are quite common and the course of GA is not easy to predict. Moreover, most therapeutic regimens have been used anecdotally and with variable success. We report the case of a 62-year-old White female patient affected by disseminated GA unsuccessfully treated with psoralen plus UVA photochemotherapy, prednisone, and cyclosporine (ciclosporin) who responded to the anti-tumor necrosis factor-α monoclonal antibody infliximab administered intravenously at a dosage of 5 mg/kg at weeks 0, 2, and 6 and thereafter at monthly intervals for 10 additional months. Most of the GA lesions improved within 8 weeks and then slowly resolved within 10 months of treatment. We suggest that infliximab may be proposed as an additional therapeutic option in the treatment of recalcitrant forms of disseminated GA.

Granuloma Annulare Treated With Rifampin, Ofloxacin, and Minocycline Combination Therapy

Granuloma annulare (GA) is a benign, usually self-limiting, dermatosis, that typically presents as asymptomatic, flesh-colored or erythematous papules, frequently arranged in an annular or arciform pattern on the distal extremities. Although localized GA is most commonly observed, a generalized or disseminated form can occur. The etiology of GA is unknown; however, multiple inciting factors have been proposed. Histologically, GA is characterized by foci of degenerative collagen associated with palisading, sometimes infiltrating granulomatous inflammation. We report 6 cases with biopsy-proved GA, resistant to the standard modalities of treatment that resolved after 3 months with monthly rifampin (600 mg), ofloxacin (400 mg), and minocycline hydrochloride (100 mg) combination therapy. Rifampin, ofloxacin, and minocycline combination therapy has been successfully used to treat patients with paucibacillary leprosy. Given reports that prolonged antibiotic agents are a useful treatment for GA, rifampin (600 mg), ofloxacin (400 mg), and minocycline hydrochloride (100 mg) combination therapy was initiated in these patients. Complete clearance of the plaques was achieved 3 to 5 months after the initiation of treatment. Some patients experienced postinflammatory hyperpigmentation. Although our treatment was effective, further studies may be needed to confirm the success of this therapeutic option for patients with recalcitrant lesions of GA.

Photodynamic Therapy for Granuloma Annulare: More than a Shot in the Dark

Background: Granuloma annulare (GA) is a benign granulomatous and inflammatory skin disorder. The pathogenesis remains enigmatic and convincingly effective treatment options are not available. Inspired by a report showing photodynamic therapy (PDT) to be effective in a single patient with GA, we sought to evaluate this benefit in a series of patients with GA. Observations: PDT was performed in 7 consecutive patients with histologically confirmed GA located at the extremities. First, 20% ALA gel was applied under an occlusive dressing for 5 h, followed by illumination with 100 J/cm² by a standard red-light source. In total, 2–3 PDT sessions were performed, with an interval of 2–4 weeks between each session. Treatment was stopped when complete remission was achieved or when GA lesions remained unchanged after 2 consecutive PDT sessions. The overall response rate was 57%. In 2 patients (29%), GA cleared completely, in 2 patients (29%) the skin lesions improved markedly and in 3 patients (43%) no clinical response could be observed. Conclusion: These promising results should be evaluated in larger controlled studies. In selected patients, PDT might be a valuable recruit for the sparse armory available to treat GA.

Widespread granuloma annulare and Hodgkin's disease

The presence of coexistent disseminated granuloma annulare (GA) and Hodgkin's disease (HD) is rare, with only six reported patients to date. We describe a patient with HD who had limited GA 2 years before the diagnosis of HD; widespread GA appeared after first-line treatment and heralded disease relapse. GA lesions showed hypermetabolic images on positron emission tomography, an interesting finding of unknown significance. We suggest a new pathophysiological mechanism for this association, i.e. that the reactive T-lymphocyte population in HD may contribute to granuloma formation through the secretion of cytokines and the subsequent upregulation of certain metalloproteinases. Diffuse cutaneous GA should raise the possibility of underlying systemic lymphoma or HD.

Open comedones overlying granuloma annulare in a photoexposed area

A 57-year-old, fair-skinned female patient with lesions of granuloma annulare located on her forearms - with signs of actinic damage - is described. No response was observed after successive treatments with topical corticosteroids and oral pentoxifylline. Four years later, the patient developed open comedones on the rim of granuloma annulare lesions. The loss of elastic fibers seen in both granuloma annulare and solar elastosis is presumed to have induced the appearance of open comedones, because of a loss of supporting properties of the dermis inducing a distension of the infundibular canal of the sebaceous follicle, as seen in the Favre-Racouchot disease and actinic comedonal plaque. Concomitantly, the patient developed insulin-dependent diabetes mellitus. Treatment with insulin resulted in the disappearance of open comedones and notably regression of lesions of granuloma annulare. Response to insulin therapy in our case supports the hypothesis that insulinopenia could participate in the development of granuloma annulare in some cases.