Unusual Adverse Effects of Immune Checkpoint Inhibitors: Autonomic Neuropathy, Palmoplantar Keratoderma, Reiter Syndrome & Myasthenia Gravis: A Case Series and Review of the Literature

The immune checkpoint inhibitors (ICIs) have transformed the standards of care in cancer treatment and has dramatically improved patient prognoses. As a result of the introduction of these novel treatments several types of adverse events related to ICIs (immune related adverse events ((irAEs)) have been observed and reported. In this case series we describe the clinical course of four patients, with unusual ICI induced toxicities. The first patient was a 59 year-old female who received chemo-immunotherapy (pembrolizumab) for stage 4- lung adenocarcinoma, and developed autonomic neuropathy (AN). The second and third patients were both 63 year-old males who also received chemo-immunotherapy (pembrolizumab) for stage 4-A lung adenocarcinoma. One of those patients developed palmoplantar keratoderma and one developed conjunctivitis, urethritis and arthritis (Reiter syndrome). The fourth patient was an 80 year-old male who received chemo-immunotherapy (pembrolizumab) for stage 3-A squamous cell carcinoma of the lung and developed myasthenia gravis.

Reactive Arthritis The Reiter-Fiessinger-Leroy Syndrome

The role of creating the expression of reactive arthritis rests with AHO in 1973, which defines reactive arthritis as an acute, unsupportive, sterile inflammatory arthropathy, arising from infections located at a distance in people with a certain genetic predisposition; the disease is systemic and, despite its name, is not limited to the joints. Reactive arthritis (RA), included in Reiter syndrome (with the classic triad of urethritis, conjunctivitis and arthritis), is a non-suppurative inflammatory joint pathology, with a minimal autoimmune component, which it is installed following intestinal or urogenital infections, mainly in people with genetic predisposition. Reactive arthritis is a form of arthritis that affects the joints, urethra, eyes and membranes and sometimes the skin and mucous membranes. This condition is also called Reiter`s syndrome, although this name only indicates a subtype. Reactive arthritis is a seronegative spondyloarthropathy, which brings together a group of disorders that cause inflammation in the body, especially in the spine - such as ankylosing spondylitis, and in the legs. The study covers a number of 20 patients (11 men, 9 women) admitted to the Rheumatology Service of the Clinical Recovery Hospital, between 2010 and 2011, aged over 20, who were diagnosed with reactive arthritis. The existence of a structural similarity between the etiological agent and the HLA-B27 molecule determines either the recognition of the disease-causing germ as a self, so that no immune response will be initiated against it and the antigen will be able to trigger the disease, or the recognition of the germ as nonself, with the triggering of an immune response aimed at both itself and against the HLA-B27 molecule carrying cells of similar structure. Reactive arthritis (RA), included in the Reiter syndrome (with the classic triad of urethritis, conjunctivitis and arthritis), is a non-suppurative inflammatory joint pathology, with a minimal autoimmune component, which is installed as a result of intestinal or urogenital infections, mainly in people with genetic predisposition.

Case: Bacillus Calmette-Guerin (BCG)-induced Reiter syndrome with an attempt at repeat BCG induction

We present a case of BCG-induced Reiter syndrome with 19-year followup, and the first instance of BCG re-induction in this cohort of patients. This was attempted given the substantial duration of disease control following the initial treatment.

A RARE COMPLICATION OF BCG IMMUNOTHERAPY

Intravesical Bacillus Calmette-Guérin immunotherapy is an effective agent for superficial bladder carcinoma. The main adverse effect of this treatment is cystitis. Arthralgia and migratory arthritis occur only in 0.5% of patients. Reiter syndrome is a very rare complication that can occur after intravesical apply of Bacillus Calmette-Guérin Immunotherapy. We report the first Albanian patient who developed Reiter’s syndrome, following intravesical Bacillus Calmette-Guérin. Diagnose of Reiter’s Syndrome was clinically based, excluding every other reason that could have caused it. Treatment was made with non-steroid and steroid anti-inflammatory drugs, followed by a full recovery result. Even though Reiter's Syndrome is a rare, but significant complication of BCG immunotherapy, it’s important to identify it in time, in order we to offer an adequate treatment.

Uveitis and medical ophthalmology

This chapter focuses on uveitis and medical ophthalmology. It details uveal anatomy, before discussing anterior uveitis, intermediate uveitis, and posterior uveitis. Next, it discusses posterior uveitis and then specific non-infectious posterior uveitides before moving on to infectious uveitis (viral, parasitic, fungal, and bacterial) and HIV-related disease. It continues by examining systemic associations with uveitis, including sarcoidosis, Behcets disease, multiple sclerosis, and the seronegative arthritides ankylosing spondylitis, Reiter syndrome, psoriatic arthritis, and inflammatory bowel disease. In addition, it discusses scleritis and episcleritis, ocular inflammatory disorders (systemic treatment, biological agents and periocular treatments, intraocular treatments), rheumatological disease, vasculitis, cardiovascular disease and the eye, and endocrine, respiratory, and skin diseases in ophthalmology.

Vasculitis

Rheumatoid arthritis is a chronic systemic inflammatory disease characterized by joint destruction. It affects 0.03% to 1.5% of the population worldwide. Women are affected 3 times more frequently than men. Its incidence peaks between the ages of 35 and 45 years; however, the age-related prevalence of the disease increases even after age 65 years. Conditions in the spondyloarthritis spectrum include ankylosing spondylitis, reactive arthritis (Reiter syndrome), arthritis related to inflammatory bowel disease, and psoriatic arthritis.

Reactive Arthritis in India: A Dermatologists' Perspective

Background: The mucocutaneous lesions in Reiter syndrome (RS) or reactive arthritis are seen quite frequently. Materials and Methods: The case records of patients admitted with the diagnosis of RS from January 2006 to December 2010 were reviewed. Data regarding the demographic details; course of musculoskeletal, mucocutaneous, and ophthalmic involvement; body surface area affected; morphology of lesions; investigations undertaken; and treatment instituted were recorded. Based on these, the disease was classified as complete or incomplete RS. Results: The case records of 11 patients were evaluated. There were seven males and four females. Only two patients had complete RS, whereas nine patients had incomplete RS. Arthritis and mucocutaneous involvement were seen in all 11 patients, whereas preceding urethritis/dysentery was seen in 4 patients and eye symptoms in 4 patients. Enthesitis was seen in eight patients (72.7%). Circinate balanitis/vulvitis was present in six patients and keratoderma blenorrhagicum in eight patients. The most frequent radiologic finding was juxta-articular osteopenia in eight patients. Conclusion: RS may not show the typical triad in all cases, although musculoskeletal disease is seen in a significant proportion of patients. In the absence of typical signs and symptoms, cutaneous manifestations may help establish the diagnosis of RS.