Follow-up of patients with sarcoidosis in an internal medicine unit from a hospital in Asturias, Spain. Analysis of extrapulmonary manifestations

Sarcoidosis is a multisystem disease of unknown origin that is characterized by non-caseating epithelioid granuloma formation within various organs, mainly the lungs [1].

The objective of this study is the analysis of sarcoidosis patients affected by pulmonary manifestation alone or extrapulmonary expression.

A retrospective review of patients diagnosed with sarcoidosis at Central University Hospital of Asturias (Oviedo, Spain), between July 1977 and January 2021. Diagnosis of sarcoidosis is based on the histopathological diagnosis and the organic affectations including clinical and radiological presentation. But the diagnosis of sarcoidosis was accepted without histological confirmation in other circumstances: Löfgren síndrome; and asymptomatic finding of typical hiliar lymphadenopatic.

Regarding organic involvement, the following have been studied: pulmonary, cutaneous, ocular, hepatic, splenic, salivary glands, otolaryngological, joints, bone, muscular, renal, phosphocalcium metabolism, neurological, cardiological and bone marrow.

In addition, the following biochemical changes were evaluated: calcium levels expressed in millimoles per liter (mmol/L), serum angiotensin-converting enzyme (SACE) in Units per liter (U/L).

Scadding JG staging system was used, as well as other radiological imaging studies such as computed tomography (CT) and positron emission tomography (PET) scan, especially to evaluate extrapulmonary involvement.

The data was recorded and analyzed using the statistical software R in version 4.1.2. The qualitative variables were summarized by their frequency distribution and the quantitative variables by the mean and standard deviation or median and interquartile range. Comparisons of qualitative variables: chi-square test. For quantitative: the U Mann-Whitney test and T-student.

A p - value < 0.05 was considered statistically significant and as a measure of association, the Odd ratio (OR), is considered statistically significant if its confidence interval (CI) does not include [1]. Those variables that reached statistical significance in the univariate analysis were introduced in the multivariate analysis.

The research protocol has been approved by the Ethics and Clinical Research Committee of the Central University Hospital of Asturias (Oviedo, Spain).

One hundred and six patients were diagnosed with sarcoidosis over forty-four years at Central University Hospital of Asturias (Oviedo, Spain), sixty-one were women (57.6%) and forty-five (42.4%) were men. Sex ratio (F/M: 1.35). The median age at diagnosis was 49.2 years (range: 38.2 - 60.1).

Table 1 shows organic affectation.

Extrapulmonary involvement was found in 84 patients (79.2%) and located exclusively (thoracic) in 22 patients (20.8%).

The chronic form of the disease, considered the presence of the disease with more than 5 years of evolution since its diagnosis, has been observed in 78 patients (73.6%). Being more noticeable in women OR 3.46 (1.36- 9.38) with p - value = 0.01.

In relation to the radiological classification by pulmonary involvement, no differences have been found between males and females (46.7% and 41%) respectively, p = 0.692.

We have also studied the relationship between radiological stages and calcium levels, in stages I, II and III, calcium levels have been normal, but all patients in stage IV presented hypercalcemia, p < 0.001, OR: 2.71 (1.35 - 4.07).

Serum values for calcium were similar in males and females (2.4 mmol/L RIQ 2.3 - 2.5), while (SACE) values in males were slightly higher (81.5 U/L RIQ 58 - 101) than in females (77 U/L RIQ 53 - 91), but without reaching statistical significance.

When comparing clinical and analytical variables: (age, sex, extrathoracic adenopathies, time of evolution, respiratory symptoms, general symptoms, serum ACE (SACE) levels, calcium and pulmonary radiological classification), between systemic and localized sarcoidosis, no statistically significant differences have been found in general, except in systemic involvement with: higher serum SACE levels with OR 1.02 (1.0 - 1.04) with a value of p = 0.04, a greater presence of extrathoracic adenopathies with a value of p = 0.031, splenomegaly and otolaryngological area involvement with values of p = 0.028 and 0.034 respectively.

In this group of pediatric patients, systemic reactions were not reported and less than one-third had local reactions. These were easily managed and dose reductions were not necessary to continue allergen immunotherapy.

In this study, the ultra-rush protocol using polymerized extracts was safe in allergic patients of pediatric age, with the advantage of the maintenance dose being reached on the first day of treatment.

There is no consensus about which dose adjustment strategy is necessary after a delay in AIT administration, and it is unclear whether some patients may tolerate longer gaps, particularly in the pediatric population [8]. In our department, after a delay of more than 2 months, both in adults and in children, it was general practice to divide the full dose for both arms without dose adjustments. The COVID-19 pandemic did not change this. The median time of interruption of AIT was 3 months and only 2% reported reactions upon reinitiating.

These findings suggest that restarting SCIT with a divided dose after a pause in administrations is safe, but we can not recommend this practice based only on our results. Furthermore, clinicians should always be aware of potential adverse reactions, even though these seem to be uncommon.

The authors point out the fact that the sample was composed of patients from only one center as a limitation of the study. It should be also mentioned that, as with any retrospective review of data, there could be possible flaws in the records interfering with the results another limitation is that sample size and power analysis was not performed.

Although the effectiveness of AIT may be compromised due to prolonged suspension of the treatment, it is important to note that despite longer interruptions, administrations may continue without compromising the safety, maintaining shorter visits and a lower number of injections.

Nonetheless, more studies with more patients are necessary to confirm our results regarding the reasonable delay for restarting AIT while maintaining its effectiveness and safety.

It is also important to emphasize that AIT administration should always be carried out in an appropriate clinical setting with trained staff capable of recognizing and managing reactions.

Author’s contribution

Ana Margarida Mesquita - Conceptualization, study design, data analysis, drafting and final writing;

Ricardo Moço Coutinho - Data analysis, drafting and final writing;

Jose Luis Plácido - Revision and supervision;

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