Cutaneous sarcoidosis with cardiac involvement

ARTICLE

Sarcoidosis is a multi-organ system disease characterized by non-caseating granulomas consisting of epithelioid cells surrounded by and interspersed with lymphocytes. There are some clinically important aspects of skin lesions in sarcoidosis. One is the ease in obtaining lesional samples which enables a histological diagnosis of sarcoidosis. A second potentially important factor is the association of a particular type of skin lesion with other organ involvement and a prognosis of sarcoidosis. Maculopapular lesions are commonly associated with acute forms of sarcoidosis, such as hilar lymphadenopathy, acute uveitis, peripheral lymph nodes, or parotid enlargement [2]. Lupus pernio (LP) is reportedly associated with chronic symptomatic pulmonary disease and upper respiratory lesions [3, 4]. In terms of the prognosis of sarcoidosis, Sones and Israel [5] reported a significantly poorer prognosis in patients with skin lesions, which was independent of race and other organ system involvement. LP and plaques are believed to be associated with the chronic course of sarcoidosis [6, 7].

The majority of patients with sarcoidosis have a good prognosis, but in rare cases the outcome is fatal, especially when cardiac lesions are observed. However, it is not known whether a relationship exists between cardiac and skin lesions of sarcoidosis. We report here five patients with cutaneous sarcoidosis where cardiac involvement was detected after cutaneous sarcoidosis was diagnosed.

Clinical subjects

All of the present patients were examined in the departments of dermatology, internal medicine and ophthalmology at our hospitals. The patients' clinical course was followed for a minimum of two years. A histological examination of the skin lesions was performed in all cases which confirmed the presence of granulomas composed principally of epithelioid cells with occasional giant cells but without caseation necrosis. Infectious conditions were eliminated and monitored by specific stains for certain micro-organisms. As Kveim reagin is not available in Japan, it could not be performed in any of the patients. A diagnosis of sarcoidosis was made based on more than one clinical finding of sarcoidosis, and more than one characteristic laboratory abnormality associated with sarcoidosis, including PPD reaction anergy, high serum levels of gamma-globulin, angiotensin converting enzyme, or lysozyme and an accumulation of gallium scintigraphy, in addition to any histological evidence of a sarcoidal granuloma. Other systemic disorders, such as malignant lymphoma, tuberculosis and berylliosis were excluded prior to making a diagnosis of sarcoidosis. All cases reported here showed intratracheal or ocular lesions as well as skin lesions.

Case 1 (Fig. 1A) had a nodular eruption on the perinasal area, while the other cases (Fig. 1B-D) had annular lesions on the face. Three patients (cases 2, 4, 5) also had scar infiltrates. Case 4 had a nodular eruption on both legs and case 5 had LP on the ear lobes. Figure 2 shows the presence of sarcoidal granulomas in a cutaneous biopsy from case 5, while Table I summarizes the clinical features of the five cases. Four patients (cases 1, 2, 4 and 5) came directly to our dermatology department after first becoming aware that they had a skin lesion. Case 3 was referred from the ophthalmology department, where she had been receiving treatment and follow-up assessment of uveitis for 8 years. None of the patients had any cardiac symptoms or abnormal findings on auscultation or electrocardiography (ECG) during periodic health examinations prior to consulting our department. Cardiac involvement was first suspected due to the appearance of mild cardiac symptoms in case 1 or abnormal findings on the ECG in the other cases. In case 1, the patient first experienced mild dyspnea three years after the diagnoses of sarcoidosis and granulomas were confirmed by a heart biopsy. She was treated with 30 mg/day of prednisolone with a tapering dosage. Cases 3 and 5 demonstrated complete auriculoventricular block (AVB) 2 years and 1 year after the appearance of skin lesions, respectively. In case 4, complete AVB was detected when the patient was admitted for examination of skin lesions. Case 2 demonstrated complete right bundle branch block (RBBB) and left bundle anterior branch block 1 year after consulting our department. All four patients with conduction disturbance were diagnosed as having cardiac sarcoidis (CaS) and subsequently underwent a permanent pacemaker implantation with 30-60 mg/day of prednisolone with tapering therapy. Since undergoing treatment, no patients have shown any further appearance of abnormal conduction or cardiac symptoms.

Discussion

The first case to show cardiac involvement of sarcoidosis and the first death due to myocardial sarcoidosis were documented by Bernstein et al. [8] in 1929 and by Gentzen [9] in 1937, respectively. Silverman et al. [10] observed cardiac involvement in 25% of all patients who died as a result of sarcoidosis and emphasized the high incidence of myocardial sarcoidosis. Sudden deaths due to ventricular tachyarrhythmias or conduction block account for 30-60% of all deaths due to sarcoidosis [11]. Recently, the frequency of primary cause of death by congestive heart failure rather than by conduction disturbances in CaS has been increasing, because of the progress in antiarrhythmic drugs and pacemaker implantation [15]. Symptoms of cardiac lesions include palpitation, dizziness, and fatigue due to arrythmia, and breathless and dyspnea due to heart failure. However, CaS is usually asymptomatic and is detected only after a diagnosis of other organ involvement is made, as in our cases.

A diagnosis of CaS is made based on heart biopsy findings. However, the evidence of granulomas provided by a heart biopsy is very low, and granulomatous lesions are often first evidenced at autopsy [12]. In our series, case 1 was confirmed as CaS by a histological examination. Case 2 had fibrosis and inflammatory cell infiltration, supporting a CaS diagnosis. The other three cases did not undergo a heart biopsy. In such cases, other laboratory tests and techniques are necessary for a diagnosis of CaS, including ECG and Holter monitor readings, echocardiography, Ga and/or TI scintigraphy and cardiac catheterization. Abnormal ECG findings characteristic of sarcoidosis patients are AVB, BBB, ventricular extrasystole, and sinus bradycardia [13]. Among these findings, AVB and RBBB are the most common changes in cardiac sarcoidosis. Cases 3, 4 and 5 in the present series had complete AVB while case 2 had BBB. Ga and TI scintigraphy reportedly reveal the uptake of radionuclides by the heart [14]. Echocardiography reveals valvular regurgitation, mitral valve prolapse, dyskinesia or hypokinesia of the left ventricle or the ventricular septum and left ventricular dilatation [15, 16]. These findings were noted in case 2 and cardiac catheterization ruled out the possibility of coronary artery disease. The efficacy of steroid therapy in eliminating these abnormal findings and in treating the cardiac dysfunction also supports a diagnosis of CaS. Thus, four of the five patients (excluding case 1) were diagnosed as CaS by the presence of cutaneous lesions, in addition to the cardiac laboratory test results, and the efficacy of steroid therapy.

The above four patients had annular lesions on the face. Histology of the lesions showed sarcoidal granulomas composed of epithelioid cells with occasional giant cells but without caseation necrosis, a finding which eliminated the possibility of other annular skin disorders such as subacute lupus, granuloma annulare and annular elastolytic giant cell granuloma. A search of Jappanese journals published in the dermatological field between 1986 and 1995 revealed 38 cases of sarcoidosis with cardiac and skin lesions. Fifteen of these cases had annular lesions. The above findings suggested that this type of skin lesion may be associated with cardiac involvement, since the frequency of annular type cutaneous lesions appears to be less than 20% in Japanese sarcoidosis patients with skin lesions. However, further examination of skin lesions in all patients with CaS is necessary to establish any potential relationship. Furthermore, the clinical appearance of sarcoidosis is well known to have racial variations [1]. In Europe, Sharma [17] reported that the most common skin lesion associated with sarcoidosis was erythema nodosum (EN) followed by maculopapular rash and plaques. In Caucasian patients in Denmark, EN was frequently seen, although plaques were the most common cutaneous lesions [7]. However, EN is seen less commonly in the United States and Japan than in Northern Europe [5, 20]. Scar infiltrates have been reported to be the most common presentation in African and Japanese patients [19, 20]. In addition, in Europe the possibility of CaS in young patients with unexplained arrhythmias or congestive heart failure should be taken into consideration [21]. However, CaS in Japan is predominantly seen in the aged as cardiac ischemia from other causes [22]. Therefore, examining the frequency of cardiac involvement in sarcoidosis patients with annular lesions in other countries should prove of great clinical benefit.

Savin [23] reported that careful cardiac examinations should be a routine procedure in all cases of established sarcoidosis, since cardiac lesions are frequently associated with rapid progression and sudden death in a previously healthy individual. The present findings support the importance placed on cutaneous lesions in the diagnosis of sarcoidosis as a systemic disease.

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