Cogan syndrome (CS) is an inflammatory disease which was described for the first time in 1934 by Morgan and Baymgamer1 and, later by David G. Cogan in 1945.2 Classified as variable vessel vasculitis by Chapel-Hill in 2012,3 it is characterized by ocular, vestibular-auditory and vasculitis symptoms, generally of the large vessels.4 This is a rare disease which presents mainly in young Caucasian males,2 and may also affect children.4

Two well differentiated, typical and atypical CS3 phenotypes have been described within the disease spectrum. The first corresponds to those patients who present with non-syphilitic interstitial keratitis, associated, or not, with conjunctivitis or subconjuntival bleeding; vestibular symptoms similar to Ménière’s syndrome with progressive hearing loss up to deafness in months, with an interval between ocular and auditory-vestibular symptoms of under 2 years. Atypical CS is characterised by ocular symptoms without interstitial keratitis or for an interval between auditory-vestibular and ocular symptoms above 2 years.5

The causes of this disease are not well known and there are few pathological or experimental references that lead to the creation of a pathogenic hypothesis.3 CS is considered to be an immune mediated disease,6 but there are no auto-antibodies or markers of clinical use. Due to the low frequency of CS, clinical and therapeutic management of this disease is based on the observations of the few published series.7

We carried out a review of the diagnostic codes in the hospital databases of 2 third level centres, which attended to a total population of approximately 800,000 inhabitants between both, to identify the diagnosed CS cases in the last 5 years (Table 1), creating a descriptive analysis of a retrospective nature.

Age at diagnosis and duration of disease was recorded, together with the main clinical, therapeutic and evaluative aspects, in accordance with the classification criteria.

Auto-antibody profiles found in the patients were described and the data of involvement of large vessels studied through the use of positron emission tomography to computerised tomography (PET/CT) in all patients. The association, described in the literature, with inflammatory bowel disease, 8 and joint involvement were recorded to a lesser extent in the published series.9

We then performed a description of treatment used, including steroids, immunosuppressant and biologic treatments, recording the frequency of each of them and the complications associated with them, as well as the most relevant data on evolution and outcomes.

Seven diagnosed cases of CS (Table 1) were described, 5 of them with the typical phenotype and 2 atypical, due, in one case, to the absence of interstitial keratitis and in the second to a period of over 2 years before the appearance of the ocular and auditory-vestibular symptoms.

Mean age at diagnosis was 42 years (32-63) with a mean follow-up from diagnosis of 47 months (7-132). The predominant ocular manifestation was the interstitial keratitis, present in 5 of the 7 cases, and with the additional presence of anterior uveitis in 5 cases (3 of them bilateral), as well as scleritis/epiescleritis in 2 patients, with no conjunctivitis in any case. In previously published series symptoms have been described in the before-mentioned ocular regions, although with a lower proportion of uveitis, and the rest of the symptom percentages being similar to those in our series.7,8

All the patients presented with auditory symptoms (deafness or hearing loss), which is in keeping with the published series.2 In this respect, there was a non response to treatment, with no improvement in the audiometric controls after treatment. The presence of vestibular symptoms (a typical trait of this disease)2,7,10,11 were constant, except in one case, where the course of the disease was not as prolonged (7 months from diagnosis), classified as atypical CS.

All patients were studied using PET/CT, with observation of large vessel symptoms in 3 cases, a higher proportion than that descried in the literature3,6,10 probably related to the systematic search for vascular involvement in our series. Imaging tests for diagnosis or follow-up was not clearly established. In our patients no subsequent complications, such as occlusive phenomena or the development of aneurisms, were recorded.

Three patients presented with joint symptoms, 2 with ankle arthritis, one with sacroiliac joints and another affecting the small joints in the hands. These symptoms presented to a similar extent to that published up until now, where arthromyalgias were described in approximately 15%–35% of cases, depending on the series.7,8

One of the patients presented with an intestinal symptom compatible with inflammatory bowel disease (IBD), which was diagnosed through biopsy. The relationship between CS and the presence of IBD has already been reported in previous publications and may be part of the clinical spectrum of CS symptoms,8,9 albeit uncommon.

Experimental data exist which describe the presence of class IgG and IgA auto-antibodies aimed against inner ear tissues and corneal tissues in patients with CS,6,11 which present similarities with the SSA/Ro and CD148 auto-antigens.6,12 These auto-anti-bodies are not normally used in clinical practice. In some patients with CS, anti-neutrophil cytoplasmic anti-bodies ANCA)12 have also been described (in our series one of the patients presented with antinuclear anti-bodies by virtue of 1/40, another patient presented with positive anti-To antibodies, and one patient presented with positive anti-PR3 antibodies, with no other clinical symptoms or associated diseases.

Regarding treatments used most frequently in the published series, corticoid therapy is the baseline initial treatment, with frequent use of corticoid pulses.13,14 in our series corticoid pulses were used in all cases. In addition to corticotheapy methotrexate was the most used immunosuppressant (6 cases), followed by azatioprine (3 cases), in a similar proportion to previously described cases.

Biologic therapies have been in use since 2000 to treat both ocular and auditory symptoms, particularly in refractory patients, with the most used agents being the anti-TNF, mostly infliximab (IFX),14,15 used in 4 of the 7 patients. Tocilizumab was used in 2 patients.

Finally, the evolution of patients in our series during the study period was diverse. The area with the best prognosis was ophthalmologic, with recovery or improvement in all cases. The auditory–vestibular area in contrast presented with torpid evolution, despite treatments administrated (corticoids, standard immunosuppressant’s or biologic therapies).

In our patients only one serious complication was recorded, a death from septic shock by bacterial endocarditis, in the patient who had received tocilizumab, after having previously been in fist line treatment with cyclophosphamide and second line treatment with methotrexate, together with a high corticoid dose.

As far as we know, this is the most numerous patient series with CS to be described on a national level, and shows general similar characteristics to published series. Joint symptoms and particularly large vessel symptoms could be more frequent in this disease than described, and based on our observation, their systematic search could bring to light silent cases.

In the absence of quality evidence, therapeutic guidelines are unallied, highlighting the need for multicentre records for this type of low incidence diseases.

The authors have no conflict of interests to declare.