Prolactin: A Mammalian Stress Hormone and Its Role in Cutaneous Pathophysiology.

The hormone prolactin (PRL) is best recognised for its indispensable role in mammalian biology, specifically the regulation of lactation. Bearing in mind that the mammary gland is a modified sweat gland, it is perhaps unsurprising to discover that PRL also plays a significant role in cutaneous biology and is implicated in the pathogenesis of a range of skin diseases, often those reportedly triggered and/or exacerbated by psychological stress. Given that PRL has been implicated in over 300 biological processes, spanning reproduction and hair growth and thermo- to immunoregulation, a comprehensive understanding of the relationship between PRL and the skin remains frustratingly elusive. In an historical curiosity, the first hint that PRL could affect skin biology came from the observation of seborrhoea in patients with post-encephalitic Parkinsonism as a result of another global pandemic, encephalitis lethargica, at the beginning of the last century. As PRL is now being postulated as a potential immunomodulator for COVID-19 infection, it is perhaps timeous to re-examine this pluripotent hormone with cytokine-like properties in the cutaneous context, drawing together our understanding of the role of PRL in skin disease to illustrate how targeting PRL-mediated signalling may represent a novel strategy to treat a range of skin diseases and hair disorders.

Ring-shaped plaque on the face.

Granulomatosis Miescher is a very rare, chronic, granulomatous (non-necrobiotic) disease. Clinical characteristics are a slowly centrifugally growing brownish plaques with partly yellowish parts and telangiectasias. Histology shows perivascular epithelioid cell granulomas with few giant cells and only isolated necrobiosis lesions.

Retroperitoneoscopic adrenalectomy may be superior to laparoscopic transperitoneal adrenalectomy in terms of costs and profit: a retrospective pair-matched cohort analysis.

BACKGROUND: A direct comparison of the cost-benefit analysis of retroperitoneoscopic adrenalectomy (RPA) versus the minimally invasive transperitoneal access (LTA) approach is currently lacking. We hypothesized that RPA is more cost effective than LTA; promising significant savings for the healthcare system in an era of ever more limited resources. METHODS: We performed a monocentric retrospective observational cohort study based on data from our Endocrine Surgery Registry. Patients who were operated upon between 2019 and 2022 were included. After pair-matching, both cohorts (RPA vs. LTA) were compared for perioperative variables and treatment costs (process cost calculation), revenue and profit. RESULTS: Two homogenous cohorts of 43 patients each (RPA vs. LTA) were identified following matching. Patient characteristics between the cohorts were comparable. In terms of both treatment-associated costs and profit, the RPA procedure was superior to LTA (costs: US$5789.99 for RPA vs. US$6617.75 for LTA, P = 0.043; profit: US$1235.59 for RPA vs. US$653.33 for LTA, P = 0.027). The duration of inpatient treatment and comorbidities significantly influenced the cost of treatment and the overall profit. CONCLUSIONS: RPA appears not only to offer benefits over LTA in terms of perioperative morbidity and length of hospital stay, but also has a superior financial cost/benefit profile.

Surgery followed by 585 nm pulsed-dye laser therapy in the treatment of granuloma faciale.

Granuloma faciale is a rare, benign skin disease characterised by solitary or multiple papules, plaques or nodules, most often occurring on the face. The skin disorder is often associated with exacerbations and remissions; spontaneous resolution seldom occurs. The treatment of granuloma faciale is challenging. Various topical and systemic treatments, but also surgical and laser therapies have been administered. A spatially confined thermal destruction of the tissue is achieved by strong absorption of haemoglobin at 585 nm wavelength. Of note, none of the presently available therapeutic interventions are particularly successful. Moreover, Granuloma faciale has the tendency to recur after treatment. Here, we present a male patient with a treatment refractory Granuloma faciale on the right cheek who was successfully treated with the combination of surgery and pulsed-dye laser therapy. Besides the good aesthetic outcome, remission was maintained after almost 1 year of follow-up.

Effect of obesity on venous blood flow in the lower limbs.

BACKGROUND AND OBJECTIVES: Although obesity is a recognized risk factor for the development of lower limb venous disease, less attention has been paid to objectively measuring the effect of centripetal obesity on blood flow in the lower limbs. PATIENTS AND METHODS: The diameter of lower limb veins and venous blood flow were measured in 44 patients (65.6 ± 12.5 years, 25 females, 19 males) with centripetal obesity and chronic venous disease. RESULTS: The mean diameter of both common femoral veins (CFV) increased significantly in the semi-supine position following elevation of the panniculus (right: ∆0.73 ± 1.21 mm; p ≤ 0.001, left: ∆1.16 ± 1.42 mm; p ≤ 0.001). Moreover, there was a significant increase in venous flow volume in the left CFV (∆62.96 ± 117.85 ml/min; p  =  0.001). Similarly, there was an increase in the diameter of left great saphenous vein (∆0.24 ± 0.41 mm; p  =  0.002), measured at the mid-thigh, when the patient lifted their abdominal panniculus. Finally, the grade of obesity correlated with the extent of the venous disease. CONCLUSIONS: These data provide preliminary evidence that centripetal obesity results in both structural and hemodynamic changes in the lower limb veins, even in the absence of classical reflux.

Evaluation of clinical and laboratory characteristics of patients with cutaneous sarcoidosis: A single-center retrospective cohort study.

Background: Cutaneous sarcoidosis is a relatively rare disease whose clinical manifestations include red-brown macules, plaques, papules and subcutaneous nodules. The skin changes may also be restricted to pre-existing scars. Cutaneous sarcoidosis can be associated with systemic organ involvement. Objectives: Aim of this retrospective study was to longitudinally investigate clinical and laboratory findings in patients with cutaneous sarcoidosis. Methods: Patients (>18 years) with histologically confirmed cutaneous sarcoidosis between January 2014 and December 2020 were included. Patient demographics, clinical features, laboratory and radiological findings, management, clinical outcomes and co-morbidities associated with cutaneous sarcoidosis were analyzed. Results: Thirty-seven patients with cutaneous sarcoidosis were identified, of whom 57% were female. The most common clinical phenotype of cutaneous sarcoidosis was papular sarcoidosis (n = 16), while plaques and nodules were present in 9 patients. In contrast, subcutaneous (n = 1) and scar-associated sarcoidosis (n = 1) were rare. Of patients with systemic disease, the cutaneous disease followed, preceded, and coincided with the development of systemic sarcoidosis in 2, 9, and 12 patients, respectively. Levels of soluble interleukin (IL)-2 receptor, angiotensin converting enzyme (ACE), and C-reactive protein (CRP) were elevated, in 76%, 21%, and 50% of the tested patients respectively and predicted systemic involvement. Hypercalcemia was present in 6% of patients. Female sex and younger age (<54 years) were significantly associated with systemic manifestations. Conlcusions: Cutaneous sarcoidosis was frequently associated with additional systemic involvement, particularly when present in young females. 24 % of patients with cutaneous sarcoidosis developed additional organ involvement during follow-up.

Disease Recurrence during Adjuvant Immune Checkpoint Inhibitor Treatment in Metastatic Melanoma: Clinical, Laboratory, and Radiological Characteristics in Patients from a Single Tertiary Referral Center.

Despite the dramatic improvements in recurrence-free survival in patients with metastatic melanoma treated with immune checkpoint inhibitors (ICI), a number of patients develop metastases during adjuvant therapy. It is not currently possible to predict which patients are most likely to develop disease recurrence due to a lack of reliable biomarkers. Thus, we retrospectively analyzed the case records of all patients who commenced adjuvant ICI therapy between January 2018 and December 2021 in a single university skin cancer center (n = 46) (i) to determine the rates of disease recurrence, (ii) to examine the utility of established markers, and (iii) to examine whether re-challenge with immunotherapy resulted in clinical response. Twelve out of forty-six (26%) patients developed a relapse on adjuvant immunotherapy in our cohort, and the median time to relapse was 139 days. Adjuvant immunotherapy was continued in three patients. Of the twelve patients who developed recurrence during adjuvant immunotherapy, seven had further disease recurrence within the observation period, with a median time of 112 days after the first progress. There was no significant difference comparing early recurrence (<180 days after initiation) on adjuvant immunotherapy to late recurrence (>180 days after initiation) on adjuvant immunotherapy. Classical tumor markers, including serum lactate dehydrogenase (LDH) and S-100, were unreliable for the detection of disease recurrence. Baseline lymphocyte and eosinophil counts and those during immunotherapy were not associated with disease recurrence. Interestingly, patients with NRAS mutations were disproportionately represented (60%) in the patients who developed disease recurrence, suggesting that these patients should be closely monitored during adjuvant therapy.

Dacarbazine in the management of metastatic melanoma in the era of immune checkpoint therapy: a valid option or obsolete?

Despite the dramatic improvement in both overall survival (OS) and progression-free survival (PFS) in patients with metastatic melanoma treated with immune checkpoint inhibitors, up to 60% will develop treatment resistance and 50% will die from their disease. Therefore, although dacarbazine is no longer a mainstay of modern melanoma management, we examined the extent to, and in which context, it may still play a role. A retrospective analysis of electronic medical records of patients who had received dacarbazine treatment between October 2014 and October 2021, following innate or acquired resistance to immune checkpoint inhibitors, was performed to determine PFS and OS and examine tolerability. Nine patients with locally advanced ( n = 1) or metastatic melanoma ( n = 8) were identified (average age: 74 years, 4 males and 5 females). The number of cycles of dacarbazine ranged from 2 to 45 (mean = 12). One-third of patients developed a complete ( n = 2) or partial ( n = 1) response, two-thirds did not respond to treatment. The median PFS time was 90 days. Common adverse events included blood dyscrasias; one patient developed a grade 3 hepatitis, although it was unclear if this was due to the chemotherapy or the preceding combined immunotherapy. Dacarbazine may still be a valid option in the setting of treatment for refractory, relapsed, or progressive disease. Future studies should focus on the immunomodulatory effects of dacarbazine on the tumor microenvironment, which could be harnessed to potentially restore sensitivity to immune checkpoint-based therapy.

Challenge of hepatitis B testing following intravenous immunoglobulin therapy in patients with autoimmune skin diseases.

Intravenous immunoglobulin (IVIg) contains pooled immunoglobulins from the plasma of healthy blood donors. All plasma samples are tested for HIV, hepatitis viruses (A, B, and C), and parvovirus B19. As part of this screening step, nucleic acid amplification technology (NAT) is used and allows the presence of specific antibodies targeting viral structures that are commonly used to test for infection status, such as anti-hepatitis B surface antigen (HBs) or anti-hepatitis B virus core (HBc) antibodies. For this reason, manufacturers point to the possibility of false-positive viral serological test results following IVIg treatment due to the passive transfer of antibodies. IVIg therapy is commonly used to manage patients with severe, treatment-refractory autoimmune skin diseases. The aim of this cohort study was to retrospectively quantify newly-discovered positive serological HBV test results after IVIg treatment in patients with autoimmune skin diseases. Between March 2018 and June 2021, 28 patients with autoimmune skin diseases received IVIg therapy, of whom 17 were longitudinally followed-up. None of the patients had evidence of active HBV infection prior to IVIg therapy. All patients (n = 17) had detectable anti-HBs antibodies and 12 patients had anti-HBc antibodies 4 weeks after commencing IVIg treatment. Passive antibody transfer seems the most likely interpretation. Nevertheless, complete serological hepatitis assessment should be performed to exclude a new infection. We recommend hepatitis screening before IVIg therapy to prevent diagnostic confusion which may arise due to passive antibody transfer.

Lichen Planus.

Lichen planus (LP) is a T cell-mediated disease affecting the stratified squamous epithelia of the skin and/or mucus membrane. Histologically, the disease is characterized by a lichenoid inflammatory infiltrate and vacuolar degeneration of the basal layer of the epidermis. LP has three major subtypes: Cutaneous, mucosal and appendageal LP. Rarely, it may affect the nails in the absence of skin and/or mucosal changes. LP may also be induced by several drugs, typically anti-hypertensive medication or be associated with infections, particularly viral hepatitis. The diagnosis is based on the clinical presentation and characteristic histological findings. Although the disease is often self-limiting, the intractable pruritus and painful mucosal erosions result in significant morbidity. The current first-line treatment are topical and/or systemic corticosteroids. In addition, immunosuppressants may be used as corticosteroid-sparing agents. These, however are often not sufficient to control disease. Janus kinase inhibitors and biologics (anti-IL-12/23, anti-IL17) have emerged as novel future treatment options. Thus, one may expect a dramatic change of the treatment landscape of LP in the near future.