Giovanni Luigi Capella

Article: Episodic aphthous stomatitis with fever, arthralgias and lymphadenopathy following multiple upper respiratory infections and pertussis in an adult: a reactive mimicker of PFAPA syndrome? - Italian Journal of Dermatology and Venereology 2022 December;157(6):536-8 - Minerva Medica - Journals

The concept of clinicopathologic dissociation is a neglected one in medicine. It refers to the unexpected, complete absence of concordance between the clinical picture and the underlying histopathologic finding. The recognition of such a phenomenon generally implies radically different treatment and follow-up choices. A rare phenomenon, it can however be encountered, especially in the field of dermatoncology and dermatology at large. It should be kept separate from clinicopathologic discordance or discrepancy, the term used by surgical pathologists to indicate the lack of expected molecular markers or to the presence of unexpected ones in the face of a given morphological diagnosis, albeit overlaps occur. More generally, the concept of clinicopathologic dissociation can be applied when a given clinical manifestation appears completely unrelated to the underlying objectively tracked primary disease. Examples are provided, and educational, ethical and medicolegal implications are briefly discussed.

In the last decade, substantial progress has been made in the study of eicosanoid autacoids, such as leukotrienes [LTs], which were already known to be heavily involved in inflammatory skin processes. The subject has extended from the detailed description of 5-lipoxygenase cascade products and regulation to the discovery of detailed interrelations among LT physiology and apparently loosely related fields such as peroxisome-proliferating activating receptors (PPARs), pro-resolving mediators, control of fibrosing processes, and nuclear signalling. Many of these advances clearly present aspects which could be relevant to experimental and clinical dermatology. Surprisingly enough, and unfortunately due at least in part to restrictive policies in off-label use of drugs all over the world, the use of available LT modulators in dermatology has remained the same as ten years ago, with the significant but marginal exception of Sjögren-Larsson syndrome. From a dermatological viewpoint, the state of the art is far from desirable. A survey of relevant advances, with special regards to medicinal chemistry topics related to anti-inflammatory intervention is provided, together with visionary proposals for future, substantial improvement in the management of patients suffering from inflammatory skin diseases, in which LT-related pathogenetic and resolving mechanism play so important a role.

A 45-year-old woman with marital and working troubles, a personal history positive for malignant melanoma, and a family history of vitiligo presented with adrenergic urticaria (AU), which at first responded to propranolol, but later became unresponsive to both ?-blockers and antihistamines. Meanwhile, rheumatoid arthritis became apparent. Treatment with corticosteroids and methotrexate led to remission of neither the rheumatologic nor the dermatologic condition. Attempts to taper the immunosuppressive treatment were invariably followed by recurrence of adrenergic urticaria, which still proved unresponsive to propranolol, as did the rheumatoid arthritis. The courses of the diseases strictly paralleled each other. Rheumatoid arthritis could have triggered adrenergic urticaria by simply adding a supplemental stress, but also by systemically activating mast cells, which are known to be involved in the pathogenesis of chronic inflammatory diseases. A brief discussion of either the dermatological manifestations of, or treatments for rheumatoid arthritis is provided, in order to illustrate the kind of clinical difficulties that such atypical patients pose to physicians. Adrenergic urticaria is an uncommon yet probably under-diagnosed form of urticaria, which is considered a form of neurogenic acute reaction mainly triggered by acute stress. The author presents a case of AU, however, that is only partially explained by a stress setting, though it is strongly associated with the course of an autoimmune disease.

"Reactive erythemas" is an umbrella term grouping several different conditions, all of which have in common the fact of being stereotypical inflammatory clinical patterns of the skin in response to disparate infectious, immune, or toxic factors. Typically, such eruptions are symmetrical or disseminated. The here reported cases are different. An elderly man underwent recurrent infections of an epidermoid cyst, accompanied by a typical erythema annulare centrifugum near the infectious focus. His grandson, aged ten months, presented with an infectious conjunctivitis, during the resolution of which two small annular lesions, compatible with annular erythema of infancy, appeared on the face. A man aged 42, respectively son and father of the two former patients, presented with an erythema multiforme target lesion proximally to an infected wound. There were no detectable predisposing factors in all cases. Familial cases of reactive erythemas have been reported. However, such limited distributions have not yet been described.