Early Serum Markers for Immune Checkpoint Inhibitor Induced Hypophysitis in Melanoma Patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activities and are widely used for the treatment of advanced cancers. However, they may lead to immune-related adverse events (irAEs) and some of them, such as hypophysitis, can be life-threatening. Here, early diagnosis is critical. METHODS: We retrospectively analyzed 40 melanoma patients who developed hypophysitis during ICI treatment with either ipilimumab and/or anti-PD1 therapy and compared them to 40 control patients who did not develop hypophysitis during the ICI treatment, matched for age, gender, type of immunotherapy, and stage. Clinical data and blood values such as LDH, CRP, TSH, T3, T4, and absolute immune cell counts were retrieved from the medical records. Patient characteristics, laboratory values, progression-free survival, and overall survival were compared between the two groups. RESULTS: Patients with ir-hypophysitis had a median age of 59 years, and most of them were male. Clinically, frequent symptoms were fatigue, headache, dizziness, and gastrointestinal symptoms such as nausea or abdominal pain. The onset of ir-hypophysitis differed much between ipilimumab- (median 8 weeks) and anti-PD1 (median 40 weeks)-induced hypophysitis (p < 0.001). At baseline, besides a slightly increased CRP level (p = 0.06), no differences were observed in patients who later developed hypophysitis compared to the control. After treatment started, hypophysitis patients showed a constant and significant decline in T4 levels from the start of therapy until diagnosis (p < 0.05), independent of the ICI treatment regime. However, a decline in T3 and TSH was only noted in patients with ipilimumab-induced ir-hypophysitis. Furthermore, serum sodium levels declined rapidly at the diagnosis of hypophysitis (p < 0.001). In addition, there was a constant increase in the absolute counts of eosinophils and lymphocytes from baseline in hypophysitis patients (p < 0.05). CONCLUSION: Ir-hypophysitis reveals different clinical pictures and onset times depending on the ICI regime used. Whereas a drop in T4 levels was indicative of developing hypophysitis independent of the ICI regime, TSH levels only declined in patients under ipilimumab-based ICI regimes. To best monitor our patients, it is important to recognize these differences.

Persistent Facial Blanching after Botulinum Toxin Injection.

We report the case of a 38-year-old male patient who presented with blanching of the face after strenuous exercise or physical exertion. The symptoms regressed in a relaxed state. Three years before presentation, he underwent botulinum toxin injections in the affected areas of the face. Facial blanching is a rare side effect of botulinum toxin injection. The postulated pathophysiology involves different transmitters mainly acetylcholine as well as co-transmitters implicated in vasodilation. Usually, facial blanching resolves shortly after waning of the botulinum toxin. However, in our case, the symptoms persisted for a longer time. Till date, therapy options for post-botulinum facial blanching are lacking, mainly due to the temporary aspect of the disease.

Multiple Keratoacanthomas after a Recent Tattoo: A Case Report.

We report on a 39-year-old man who presented with seven skin lesions on the right thigh 3 weeks after receiving a large tattoo which included red and black pigments. Initially, the lesions grew fast, later their growth stabilized. Histopathology showed well-circumscribed symmetric tumors with a central keratin-filled crater along with further trademarks of a keratoacanthoma. The patient had previously had multiple tattoos with no history of similar lesions. PCR analysis of one of the lesions revealed the presence of human papillomavirus 6. All lesions were excised with a safety margin. A 3-month follow-up revealed no further lesions.

Cutaneous manifestations in Moyamoya angiopathy: A review.

BACKGROUND AND PURPOSE: Moyamoya angiopathy (MA) is a progressive cerebrovascular disease with a poorly understood pathophysiology. It is mainly characterized by progressive bilateral stenosis of the terminal intracranial part of the supraclinoid internal carotid arteries and the proximal parts of the middle and anterior cerebral arteries. This results in early-onset ischemic or hemorrhagic strokes. The disease may be idiopathic (known as Moyamoya disease) or associated with other heritable or acquired conditions, including type 1 neurofibromatosis or other RASopathies, sickle cell disease, Down syndrome, or autoimmune disorders (known as Moyamoya syndrome). Apart from the brain, other organ manifestations including cutaneous ones have also been described in MA patients. MATERIALS AND METHODS: A literature research on PubMed was performed for articles mentioning the cutaneous association in MA and published between 1994 and October 2020. CONCLUSION: The present review summarizes the cutaneous associations as well as the coincidental dermatological findings seen in MA patients. Those include changes in the epidermis, dermis, or skin appendages for example café-au-lait spots, hypomelanosis of Ito, livedo racemosa, hemangiomas, premature graying of hair, chilblains etc.

A Case of Extensive Grover's Disease in a Patient with a History of Multiple Non-Melanoma Skin Cancers.

We report on a 69-year-old man who presented with itching and erythematous papules on his torso and extremities, which were resistant to topical therapy with antibiotics and steroids. Physical examination revealed multiple erythematous papules on his back, neckline, and lower extremities. The lesions had appeared 4 years earlier and usually worsened with heat or extensive sweating. Histopathology of previous skin biopsies had shown multiple cutaneous squamous cell carcinomas or was non-conclusive. Thus, a re-biopsy was performed, revealing acanthosis and focal acantholytic dyskeratosis. These clinical and anamnestic findings lead to the diagnosis of extensive Grover's disease (GD). Oral therapy with isotretinoin 30-mg QD led to the regression of the skin lesions. Topical adapalene, as well as topical corticosteroids, were later prescribed for maintenance therapy.