Images in clinical medicine. Geographic tongue

A 61-year-old man was referred for treatment of painless white lesions on his tongue that had appeared 1 month earlier

Giant cell arteritis presenting as scalp necrosis

The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness

Adult-onset Still's disease with atypical cutaneous manifestations

The diagnosis of adult-onset Still's disease (AOSD) can be very difficult. There are no specific tests available, and diagnosis is usually based on a symptom complex and the well-described typical evanescent rash seen in the majority of patients. However, in recent years, other atypical cutaneous manifestations of AOSD have been reported. These atypical skin eruptions often present in addition to the typical evanescent rash but may also be the only skin manifestation, resulting in delayed diagnosis because of under-recognition. In this study, we present 3 new cases of AOSD with atypical cutaneous manifestations diagnosed during a 30-year period in our department and review 78 additional cases previously reported (PubMed 1990-2016). These 81 patients form the basis of the present analysis. The overall prevalence of atypical cutaneous manifestations in our AOSD population was 14%. These manifestations may appear at any time over the course of the disease, and usually occur in patients who have persistent and severe disease, with a considerable frequency of clinical complications (23%), including serositis, myopericarditis, lung involvement, abdominal pain, neurologic involvement, and reactive hemophagocytic syndrome. The most representative and frequent lesion among the nonclassical skin rashes is the development of persistent pruritic papules and/or plaques. Interestingly, these lesions show a distinctive histological pattern. Other, less frequently observed lesions include urticaria and urticaria-like eruptions, generalized or widespread non-pruritic persistent erythema, vesiculopustular eruptions, a widespread peau d'orange appearance of the skin, and edema of the eyelids mimicking dermatomyositis without any accompanying skin lesion. The great majority of these patients required medium or high doses of glucocorticoids (including intravenous methylprednisolone pulse therapy in some cases) and, in nearly 40%, a more potent or maintenance immunotherapy with immunosuppressant drugs and/or biologic agents (mainly anakinra or tocilizumab) to control or manage symptoms because of a polycyclic or chronic course. The development of atypical cutaneous manifestations seems to be associated with a potentially worse prognosis, with a mortality rate reaching 8% primarily because of infectious complications related to immunosuppressive therapy. In conclusion, the appearance of atypical cutaneous manifestations is not uncommon in AOSD. Recognition of this clinical variant is crucial for the early diagnosis of AOSD, as it might imply persistent disease activity and the need for more aggressive treatment

PI3K (Phosphatidylinositol 3-Kinase) activation and endothelial cell proliferation in patients with hemorrhagic hereditary telangiectasia type 1

Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT

Adrenomedullin as a potential biomarker involved in patients with hereditary hemorrhagic telangiectasia

Background: Adrenomedullin (AM) is a vasoactive peptide mostly secreted by endothelial cells with an important role in preserving endothelial integrity. The relationship between AM and hereditary hemorrhagic telangiectasia (HHT) is unknown. We aimed to compare the serum levels and tissue expression of AM between HHT patients and controls. Methods: Serum AM levels were measured by radioimmunoassay and compared between control and HHT groups. AM levels were also compared among HHT subgroups according to clinical characteristics. The single nucleotide polymorphism (SNP) rs4910118 was assessed by restriction analysis and sequencing. AM immunohistochemistry was performed on biopsies of cutaneous telangiectasia from eight HHT patients and on the healthy skin from five patients in the control group. Results: Forty-five HHT patients and 50 healthy controls were included, mean age (SD) was 50.7 (14.9) years and 46.4 (9.9) years (p = 0.102), respectively. HHT patients were mostly female (60% vs 38%, p = 0.032). Median [Q1-Q3] serum AM levels were 68.3 [58.1-80.6] pg/mL in the HHT group and 47.7 [43.2-53.8] pg/mL in controls (p<0.001), with an optimal AM cut-off according to Youden's J statistic of 55.32 pg/mL (J:0.729). Serum AM levels were similar in the HHT subgroups. No patient with HHT had the SNP rs4910118. AM immunoreactivity was found with high intensity in the abnormal blood vessels of HHT biopsies

Giant cell arteritis presenting as scalp necrosis

The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness

Giant cell arteritis presenting as scalp necrosis

The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness

PI3K (Phosphatidylinositol 3-Kinase) activation and endothelial cell proliferation in patients with hemorrhagic hereditary telangiectasia type 1

Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT

PI3K (Phosphatidylinositol 3-Kinase) activation and endothelial cell proliferation in patients with hemorrhagic hereditary telangiectasia type 1

Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT