An Uncommon Coexistence of Sarcoidosis and Cutaneous Leukocytoclastic Vasculitis in an Adult.

The skin is the second most commonly involved organ after pulmonary system in sarcoidosis, a multisystemic granulomatous disease. Cutaneous small-vessel vasculitis (leukocytoclastic vasculitis [LCV]) is a disorder characterized by neutrophilic inflammation of small blood vessels. Although the skin is the organ where LCV is seen most frequently, extracutaneous involvements are also seen. Herein, we present a coexistence of sarcoidosis and cutaneous LCV, which is an uncommon condition in adult. Copyright:

Introduction

Sarcoidosis is a multisystem, granulomatous, and autoimmune disease of unknown etiology. Although respiratory system is involved most commonly, skin, musculoskeletal, ophthalmologic, cardiac, neurologic, gastrointestinal, and renal involvements can be seen.[1] Skin involvement in sarcoidosis may cause numerous lesions including lupus pernio lesions seen more frequently on the face, annular and plaque-like lesions, and maculopapular or nodular lesions.[1] Sarcoidosis-associated vasculitis is rare; however, granulomatous lesions can be encountered in small and large vessels. Vasculitic lesions can be limited to the skin, and the signs of systemic vasculitis can also be seen.[1] Leukocytoclastic vasculitis (LCV) is characterized by inflammation of small vessels. Drugs, infections, malignant conditions, and systemic inflammatory diseases play a role in the etiology; however, the etiology is sometimes unknown. Moreover, conditions associated with LCV include sarcoidosis, Wegener's granulomatosis, rheumatoid arthritis, and polyarteritis nodosa.[2] Palpable purpuras localized particularly in the lower limbs are the typical signs of LCV. Histopathologically, perivascular neutrophilic infiltrates are seen in the cutaneous postcapillary venules together with fibrinoid deposits in and around the vascular wall, endothelial swelling, and erythrocyte extravasation.[2] The lesions are usually asymptomatic but may be accompanied by tenderness, sense of burning, and itching. Weakness, joint and muscle pain, arthritis, abdominal pain, and fever can be seen in acute phase.[2] Herein, we present a coexistence of sarcoidosis and cutaneous LCV, which is an uncommon condition in adults.

Case Report

A 40-year-old female patient visited our rheumatology polyclinic in December 2015 for bilateral lower extremity pain. She had multiple, irregular, nonblanching 1–3 cm purpuric lesions on yellowish ground more intensively on both the legs and ankles for 3 years [Figure 1]. She was referred to a dermatology clinic for skin biopsy. On the histopathological examination of the skin biopsy (tru-cut, punch biopsy of the skin, 0.4 cm in diameter and 0.4 cm in depth), which was taken based on the macroscopic prediagnosis of pigmented purpuric dermatosis, basket-like hyperkeratosis and mild acanthosis were observed in the epidermis. In the papillary dermis and mid-dermis, fibrinoid necrosis was observed in the walls of small vessels, capillaries, arterioles, and venules together with polymorphonuclear leukocytes infiltrating the vascular wall, edema, erythrocyte extravasation, and mixed inflammation composed of polymorphonuclear leukocytes and lymphocytes. Periodic acid–Schiff staining was negative for microorganism; direct immunofluorescence staining was negative for immunoglobulin (Ig) A, IgM, or IgG. C3 staining was positive in the vascular wall. The reported diagnosis was cutaneous small-vessel vasculitis with predominating polymorphonuclear leukocytes [Figure 2]. For differential diagnosis, posteroanterior chest radiography showed increased opacity consistent with bilateral hilar lymphadenopathy and right paratracheal lymphadenopathy [Figure 3], and thoracic computed tomography revealed multiple mediastinal lymphadenopathies (right paratracheal [Stations 4R and 7] 15-mm lymphadenopathy and 5-mm subpleural nodule in the lateral aspect of the middle-right lobe of the lung) [Figure 4a and b]. Fiber-optic bronchoscopy revealed no endobronchial lesion. The transcarinal needle aspiration biopsy showed no pathology. Mucosal and transbronchial biopsies could not be performed as the patient's oxygen saturation decreased during fiber-optic bronchoscopy. Results of the bronchoalveolar lavage (BAL) analysis were as follows: total cell: 330/mm3, lymphocyte: 15/mm3 (38%), neutrophil: 66/mm3 (20%), macrophage: 132/mm3 (40%), eosinophil: 7/mm3 (2%), live cell: 92.12%, CD3: 95.69%, CD4: 84.72%, CD8: 10.03%, and CD4/CD8 ratio: 8.44. For BAL fluid, acid fast bacilli were negative microscopically, and the culture in Löwenstein–Jensen agar showed no growth. Biopsy material taken mediastinoscopically from the right lower paratracheal lymphadenopathy showed no malignancy but nonnecrotizing granulomatous inflammation [Figure 5]. Routine hematologic and biochemical tests were normal. Angiotensin-converting enzyme level was 52 U/L. Her spirometry was normal. All autoantibody tests (including anti-Ro/SSA, anti-human leukocyte antigen, anti-DR3, anti-DNA, anti-Sm, anti-RNP, and antineutrophil cytoplasmic antibodies) that were performed to eliminate systemic vasculitis were negative. She had no history of medication. In the upper and lower extremities, electrophysiological studies were normal. She had no sign of any infectious diseases and her anti-HIV antibody, hepatitis B virus surface antigen, and anti-HCV antibody tests were negative. Ophthalmologic, cardiologic, and neurologic examinations revealed no extrapulmonary involvement. The patient diagnosed with Stage I sarcoidosis has still been followed without any symptom.

Figure 1

Irregular, nonblanching, 1–3 cm multiple purpuric lesions on yellowish ground (a) on the leg and (b) on the ankle

Figure 2

Histopathological examination of skin biopsy: (a) fibrinoid necrosis in the small capillary walls and polymorphonuclear leukocytes infiltrating the vascular wall (H and E, ×400); (b) basket-like hyperkeratosis and mild acanthosis in the epidermis. Fibrinoid necrosis in the small capillary walls, polymorphonuclear leukocytes infiltrating the vascular wall, edema, and erythrocyte extravasation in the papillary dermis (H and E, ×100)

Figure 3

Bilateral hilar and right paratracheal lymphadenopathy on posteroanterior chest X-ray

Figure 4

Thoracic computed tomography (contrast enhanced); (a) 15-mm lymphadenopathy in the right paratracheal (Stations 4R and 7) through the mediastinal window; (b) 5-mm subpleural nodule in the lateral aspect of the middle-right lobe of the lung through the parenchymal window

Figure 5

Histopathologic images of the mediastinoscopic materials; (a) confluent nonnecrotizing granulomatous structures infiltrating lymph node (H and E, ×40); (b) nonnecrotizing granulomatous structures (H and E, ×100); (c) confluent nonnecrotizing granulomatous structures (H and E, ×100)

Discussion

Herein, a case of sarcoidosis accompanied by cutaneous LCV was reported. The diagnosis of sarcoidosis was established by pathological examination of the mediastinoscopic material. In addition, CD4/CD8 ratio in the BAL fluid was 8.44. Although most biomarkers are not sensitive and specific enough in diagnosing sarcoidosis, they provide significant clue when evaluated together with clinical signs.[3] CD4/CD8 ratio in BAL fluid is also investigated, although it is debatable as a diagnostic marker of sarcoidosis. CD4/CD8 ratio >3–4 is associated with the diagnostic sensitivity of 50%–60% and specificity of ~95%.[3] Some sarcoidosis patients show classical presentation and do not require confirmation with tissue biopsy. Tissue biopsy is only required for suspicious cases. Obtaining intrathoracic materials through transbronchial biopsy or obtaining samples from mediastinal lymph nodes through ultrasound-guided biopsy results in high diagnostic yield with low complication rates.[4] Our case had bilateral hilar lymphadenopathy and multiple mediastinal lymphadenopathies; hence, the diagnosis of sarcoidosis was confirmed by tissue biopsy. The skin is the second most frequently involved organ after pulmonary system in sarcoidosis. Skin lesions are present in about 30% of patients.[5] Our case also had skin lesions for 3 years. Cutaneous vasculitis can manifest with various lesions including urticaria, infiltrative erythema, petechiae, purpura, purpuric papules, hemorrhagic vesicles and bullae, nodules, livedo racemosa, deep (punched out) ulcers, and digital gangrene depending on the size of involved vessel and the width of vascular bed. Skin biopsy is the gold standard in diagnosing vasculitis.[6] LCV is characterized by neutrophilic inflammation predominantly limited to small blood vessels. Skin is the most common site of LCV; however, extracutaneous involvement can also be seen.[7] Cutaneous LCV commonly manifests with palpable purpura.[7] Our case also had purpuric lesions in both lower extremities and ankles. Coexistence of LCV and sarcoidosis is reported in the literature only as case reports. Aractingi et al.[8] reported a case in 1993 and stated that there were only four sarcoidosis-associated LCV cases published previously. The common characteristics of those cases were the cutaneous manifestations (purpuric or annular lesions and nodules) and the presence of mediastinal lymph nodes, as was in our case. Cecchi and Giomi[9] reported a sarcoma case with LCV manifesting as annular lesions. García-Porrúa et al.[10] reported a sarcoidosis-associated LCV case and attracted physicians' attention to the likelihood of LCV as a presenting manifestation of sarcoidosis. Recently, Numakura et al.[11] reported simultaneous development of sarcoidosis and LCV in a 23-year-old male patient with refractory Crohn's disease during infliximab therapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

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Conflicts of interest

There are no conflicts of interest.