and primarily the rich plasma cell infiltrate were consistent with benign tertiary syphilis.Serology resulted positive for both treponemal and non-treponemal tests: Treponema pallidum hemagglutination assay (TPHA) titre was 1:10240 and venereal disease research laboratory (VDRL) titre was 1 : 64; anti-T.pallidum IgM antibodies were also positive. Neurological, ophthalmological and cardiological examination, brain magnetic resonance imaging and echocardiogram were normal. However, cerebrospinal fluid (CSF) testing revealed mononuclear pleocytosis (cell count 9 lL), reactive TPHA with titre of 1 : 1280, intrathecal CSF IgG-Index of 0.9 and TPHA index of 136. Anti-T.pallidum IgM antibodies in CSF resulted negative.The patient was ultimately diagnosed with asymptomatic neurosyphilis and therefore treated with aqueous penicillin G, four million units intravenously every 4 h for 14 days. The cutaneous lesions resolved with scarring in 4 weeks (Fig. 1c,d); after 6 months, in the serum, VDRL and TPHA titres declined six-fold and anti-T.pallidum IgM antibodies resulted weakly positive.This case was interesting not only for the deceiving patient's history but especially for the clinical aspect of the cutaneous lesions, given the rarity, nowadays, of benign tertiary syphilis (gummas) in clinical practice. Syphilitic nodules may mimic lymphoproliferative disorders, granulomatous disorders, deep fungal and mycobacterial infections. 1,2,5,6 Close collaboration with the pathologist and finding a rich plasma cell infiltrate helped solve this case. Notably, even in absence of any neurological signs or symptoms, our patient had a neurologic involvement confirmed by CSF abnormalities. CSF testing is crucial for the correct diagnosis and therapeutic approach, also in case of asymptomatic neurosyphilis. 6 Even if the patient's history is not evocative for STDs, as in our case, syphilis should be considered when approaching granulomatous lesions of unclear nature.
The autosomal recessive congenital ichthyoses (ARCI) are a nonsyndromic group of cornification disorders that includes lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. To date mutations in ten genes have been identified to cause ARCI: TGM1, ALOX12B, ALOXE3, NIPAL4, CYP4F22, ABCA12, PNPLA1, CERS3, SDR9C7, and SULT2B1. The main focus of this report is the mutational spectrum of the genes ALOX12B and ALOXE3, which encode the epidermal lipoxygenases arachidonate 12-lipoxygenase, i.e., 12R type (12R-LOX), and the epidermis-type lipoxygenase-3 (eLOX3), respectively. Deficiency of 12R-LOX and eLOX3 disrupts the epidermal barrier function and leads to an abnormal epidermal differentiation. The type and the position of the mutations may influence the ARCI phenotype; most patients present with a mild erythrodermic ichthyosis, and only few individuals show severe erythroderma. To date, 88 pathogenic mutations in ALOX12B and 27 pathogenic mutations in ALOXE3 have been reported in the literature. Here, we presented a large cohort of 224 genetically characterized ARCI patients who carried mutations in these genes. We added 74 novel mutations in ALOX12B and 25 novel mutations in ALOXE3. We investigated the spectrum of mutations in ALOX12B and ALOXE3 in our cohort and additionally in the published mutations, the distribution of these mutations within the gene and gene domains, and potential hotspots and recurrent mutations.
Summary
Ichthyoses comprise a heterogeneous group of hereditary disorders of keratinization characterized by a highly varied clinical picture. A distinction is made between common hereditary ichthyoses (ichthyosis vulgaris and X‐linked ichthyosis), which usually manifest themselves in the first year of life, and rare, sometimes severe congenital ichthyoses. Patients with very mild symptoms often do not even realize they have ichthyosis. The diagnosis is usually based on clinical evaluation. Molecular genetic testing as well as histological and electron microscopic studies may aid in confirming the diagnosis. Mapping a family tree is also diagnostically useful. Besides skin manifestations, important aspects of the clinical examination and history include disease onset, presence of a collodion membrane at birth as well as the presence of hair anomalies and extracutaneous signs and symptoms.
Rigorous hydration of the skin (several times a day) and balneotherapy are the mainstay of ichthyosis treatment. For patients with severe disease, systemic acitretin treatment should be considered on a case‐by‐case basis. While ichthyoses are generally limited to the skin, there are syndromic forms that may affect other organs and that require interdisciplinarity cooperation. Although ichthyoses remain incurable, they can be managed well with symptomatic treatment. However, such treatment is frequently time consuming and expensive. In the future, novel therapeutic approaches might include enzyme replacement and gene therapies as well as antiinflammatory drugs.
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