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Successful Treatment of Systemic Sarcoidosis with Tranilast
Lifang Hu, Feng Yang, Xinzheng Lu and Maihua Hou*
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, China
Volume 1 Issue 1 - 2018
Received Date: 11 June 2018
Accepted Date: 30 June 2018
Published Date: 07 June 2018
1. Absract
Although the effectiveness of tranilast in cutaneous sarcoidosis has been reported, its recorded
adoption in systemic sarcoidosis is finite. We report a case of huge subcutaneous sarcoidosis
with multiple organ involvement and systemic symptoms relieved quickly after the treatment of
tranilast, suggesting that tranilast is expected to become the first-line therapy of sarcoidosis as
for its less side effect.
Annals of Clinical and Medical
Case Reports
Citation: Yang F, Wang F, Li K and Hou M, Successful Treatment of Systemic Sarcoidosis with Tranilast. An-
nals of Clinical and Medical Case Reports. 2018; 1(1): 1-3
United Prime Publications: http://unitedprimepub.com
*Corresponding Author (s): Maihua Hou, Department of Dermatology, The First Affili-
ated Hospital of Nanjing Medical University, Jiangsu 210029, China, Tel: +86 13776635881;
Email: houmaihua@jsph.org.cn
Case Report
2. Keywords
Systemic sarcoidosis; Tranilast;
Subcutaneous nodules
3. Intuduction
Sarcoidosis is a systemic disease of undetermined etiology, char-
acterized by the presence of non-caseating epithelial granuloma
involving multiple organs of the body, most frequently seen in
lungs, lymph nodes, skin and eyes. Oral corticosteroid is a first-
line treatment, but its long-term use may bring many side effects,
especially in those with underling diseases such as diabetes. There
has been reports showing potential effects of tranilast in cutane-
ous sarcoidosis [1,2].We present a case of a 64-year-old Chinese
female with systemic sarcoidosis accompanied by systemic symp-
toms including chest pain, dry cough and dyspnea relieved sig-
nificantly after the treatment of tranilast. So far, this is the first
time to report a case of systemic sarcoidosis treated with tranilast,
and we hope the presentation will stimulate new investigations
into this troublesome clinical problem.
4. Case Presentation
	 A 64-year-old Chinese female was referred to our der-
matology clinic with subcutaneous nodules of 1 months’ dura-
tion, large and firm on her both forearms, covered by normal-ap-
pearing skin, accompanied with systemic symptoms of chest pain,
dry cough and dyspnea, which aggravated gradually for 1 months.
She was not taking any oral medications before and the lesions
of bilateral forearm did not experience trauma or injection. The
findings of pulmonary CT scanning and ultrasound at different
time point is compared in (Table 1).
At the beginning of therapy Tranilast (0.3 g/day), 3 months later Tranilast (0.3 g/day), 2 years later
Clinical Manifesta-
tion
large and firmly subcutaneous nodules on her
both forearms
The skin turned soft and the nod-
ules could not be touched.
normal
Skin Ultrasound
Ultrasonography indicated that the echo of the
subcutaneous fat layer of bilateral forearms
was not uniform ranging about 20*
5*
0.9cm in
the left forearm and 20*
5.9*
0.7cm in the right.
The echo of the subcutaneous fat
layer of bilateral forearms ranges
about 20*
3.5*
0.6cm in the left and
20*
2.6*
0.5cm in the right.
normal
Abdominal Ultra-
sound
The abdominal ultrasonography revealed sple-
nomegaly with a size of 14.8*
4.4cm, smooth
capsule and evenly distributed internal echo.
No obvious change.
The size of spleen was only 11.4*
4.8cm,
evidently smaller than before.
Pulmonary CT
Pulmonary CT scanning revealed multiple en-
larged lymph nodes in the mediastinum and the
largest of which under the tracheal protuber-
ance was about 2.6cm in size.
No obvious change.
Pulmonary CT scanning revealed
multiple enlarged lymph nodes in the
mediastinum and the largest of which
under the tracheal protuberance was
about 1.0 cm in size.
Table 1: Examination results at different time points of therapy.
Copyright ©2018 Hou M. This is an open access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and build upon your work non-commercially. 2
Volume 1 Issue 1 -2018 Case Report
Biopsy examination of a subcutaneous nodule of forearm re-
vealed non-necrotizing epithelioid cell granulomas in the der-
mis, epithelioid cells, giant cells and cellulose were observed.
Special stains for acid-fast bacilli and fungi were negative. The
histopathology of intrathoracic lymph nodes revealed epithelioid
cell granulomas. Ophthalmological examination indicated the
age-related macular degeneration which is not associated with
sarcoidosis. Laboratory tests including peripheral blood routine,
hepatorenal function, angiotensin-converting enzyme (ACE),
and anti-nuclear antibody (ANA), serum calcium were all nor-
mal. Tuberculin test was negative. The result of electrocardio-
gram was normal. His superficial lymph nodes were not enlarged
(Figure 1).
Figure 1: Pulmonary CT revealed that the largest lymph node turned signifi-
cantly smaller than before.
Based upon the clinical and histopathologic findings described
above, the patient was diagnosed with subcutaneous sarcoidosis
with systemic involvement. Oral administration of tranilast 300
mg per day was begun. The skin became soft and nodules could
not be touched (still could be detected by ultrasound). Moreover,
the symptoms of chest pain, dry cough and dyspnea disappeared
entirely after 3 months of therapy (Figure 2).
Two year later, ultrasonic manifestations of bilateral forearms re-
turned to normal. At the same time, chest CT and abdominal ul-
trasound were reexamined and the lesions both become smaller
than before. During these courses of treatment, no side-effect
has been recognized and the patient continues taking tranilast
300mg per day. So far, the patient has been followed up.
The patient was then treated with 40 mg methylprednisolone
along with anticoagulants (warfarin, low molecular heparin)
and an antiplatelet (aspirin), which led to a dramatic reduction
in his peripheral blood eosinophilia (at the absolute count of
0.63×109/L) and clearance of his skin rash in the first week of
treatment. Thus far, follow-up has been consistent.
5. Discussion
Sarcoidosis is a systemic disease characterized by the presence of
non-caseating epithelial granuloma involving multiple organs of
the body. There have been some reports showing the effective-
ness of tranilast in treating cutaneous lesions in some cases of
granulomatous disorders such as granuloma annulare, and sar-
coidosis [1,2]. It has been demonstrated that tranilast decreases
adhesion molecules such as ICAM-1 and LFA-1 expression on
monocytes, inhibits the release of chemical mediators and affects
the monocyte macrophage-lineage cells, resulting in resolution
of the granulomatous lesions [3]. The major mode of the drug’s
efficacy appears to be the suppression of the expression and/or
action of the TGF-β pathway, inhibiting collagen synthesis in fi-
broblasts [4].
In this case, after the treatment of tranilast for 3 months, subcu-
taneous nodules could not be touched and symptoms of chest
pain, dry cough and dyspnea disappeared completely, which sug-
gests that tranilast is effective in treating systemic sarcoidosis and
may improve clinical symptoms after three months. After nearly
two years, the ultrasonic findings of subcutaneous nodules disap-
peared completely. But the manifestations of pulmonary lymph
nodes and spleen, have not returned to normal. Treated with tra-
nilast, subcutaneous nodules vanished ahead of internal organs,
so it can be inferred that enlarged lymph nodes and spleen were
as firm as subcutaneous nodules at the beginning but turned soft
along with therapy, resulting in clinical remission. However, it
takes a long time to observe all internal organs to return to nor-
mal and the time is up to the range of involvement. Our patient
still needs further follow-up observation. Whether it will relapse
after stopping the medicine is still a question. There has been
no report of sarcoidosis invovling several organs with systemic
symptoms of fatigue and respiratory symptom treated successful-
ly with tranilast. Although we report only a single case, tranilast
may be a reasonable treatment option for not only cutaneous sar-
Figure 2: Skin ultrasound indicated that after nearly 2 years of treatment, sub-
cutaneous nodules returned to normal.
United Prime Publications: http://unitedprimepub.com 3
Volume 1 Issue 1 -2018 Case Report
coidosis but can relief other sarcoidosis symptoms.
6. Compliance with Ethical Standards
Funding: This article was funded by Jiangsu Provincial Six Talent
Peaks (2013-WSN-031) and Jiangsu Education Science 12th Five-
Year programe (D/2013/01/015).
7. Conflict of Interest
We declare that there is no conflict of interest.
8. Ethical approval
This article does not contain any studies with animals performed
by any of the authors.
References
1. Nakahigashi K, Kabashima K, Akiyama H, Utani A, Miyachi Y. Re-
fractory cutaneous lichenoid sarcoidosis treated with tranilast. JAAD.
2010:63(1):171-2.
2. Yamada H, Ide A, Sugiura M, Tajima S. Treatment of cutaneous sar-
coidosis with tranilast. J Dermatol. 1995:22(2):149-52.
3. Mizuno K, Okamoto H, Horio T. Inhibitory influences of tranilast
on multinucleated giant cell formation from monocytes by superna-
tant of concanavalin A-stimulated mononuclear cells. J Dermatol Sci.
2000:24(3):166-70.
4. Yamada H, Tajima S, Nishikawa T, Murad S, Pinnell SR. Tranilast, a
selective inhibitor of collagen synthesis in human skin fibroblasts. J Bio-
chem. 1994:116(4):892-7.

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Successful Treatment of Systemic Sarcoidosis with Tranilast

  • 1. Successful Treatment of Systemic Sarcoidosis with Tranilast Lifang Hu, Feng Yang, Xinzheng Lu and Maihua Hou* Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, China Volume 1 Issue 1 - 2018 Received Date: 11 June 2018 Accepted Date: 30 June 2018 Published Date: 07 June 2018 1. Absract Although the effectiveness of tranilast in cutaneous sarcoidosis has been reported, its recorded adoption in systemic sarcoidosis is finite. We report a case of huge subcutaneous sarcoidosis with multiple organ involvement and systemic symptoms relieved quickly after the treatment of tranilast, suggesting that tranilast is expected to become the first-line therapy of sarcoidosis as for its less side effect. Annals of Clinical and Medical Case Reports Citation: Yang F, Wang F, Li K and Hou M, Successful Treatment of Systemic Sarcoidosis with Tranilast. An- nals of Clinical and Medical Case Reports. 2018; 1(1): 1-3 United Prime Publications: http://unitedprimepub.com *Corresponding Author (s): Maihua Hou, Department of Dermatology, The First Affili- ated Hospital of Nanjing Medical University, Jiangsu 210029, China, Tel: +86 13776635881; Email: houmaihua@jsph.org.cn Case Report 2. Keywords Systemic sarcoidosis; Tranilast; Subcutaneous nodules 3. Intuduction Sarcoidosis is a systemic disease of undetermined etiology, char- acterized by the presence of non-caseating epithelial granuloma involving multiple organs of the body, most frequently seen in lungs, lymph nodes, skin and eyes. Oral corticosteroid is a first- line treatment, but its long-term use may bring many side effects, especially in those with underling diseases such as diabetes. There has been reports showing potential effects of tranilast in cutane- ous sarcoidosis [1,2].We present a case of a 64-year-old Chinese female with systemic sarcoidosis accompanied by systemic symp- toms including chest pain, dry cough and dyspnea relieved sig- nificantly after the treatment of tranilast. So far, this is the first time to report a case of systemic sarcoidosis treated with tranilast, and we hope the presentation will stimulate new investigations into this troublesome clinical problem. 4. Case Presentation A 64-year-old Chinese female was referred to our der- matology clinic with subcutaneous nodules of 1 months’ dura- tion, large and firm on her both forearms, covered by normal-ap- pearing skin, accompanied with systemic symptoms of chest pain, dry cough and dyspnea, which aggravated gradually for 1 months. She was not taking any oral medications before and the lesions of bilateral forearm did not experience trauma or injection. The findings of pulmonary CT scanning and ultrasound at different time point is compared in (Table 1). At the beginning of therapy Tranilast (0.3 g/day), 3 months later Tranilast (0.3 g/day), 2 years later Clinical Manifesta- tion large and firmly subcutaneous nodules on her both forearms The skin turned soft and the nod- ules could not be touched. normal Skin Ultrasound Ultrasonography indicated that the echo of the subcutaneous fat layer of bilateral forearms was not uniform ranging about 20* 5* 0.9cm in the left forearm and 20* 5.9* 0.7cm in the right. The echo of the subcutaneous fat layer of bilateral forearms ranges about 20* 3.5* 0.6cm in the left and 20* 2.6* 0.5cm in the right. normal Abdominal Ultra- sound The abdominal ultrasonography revealed sple- nomegaly with a size of 14.8* 4.4cm, smooth capsule and evenly distributed internal echo. No obvious change. The size of spleen was only 11.4* 4.8cm, evidently smaller than before. Pulmonary CT Pulmonary CT scanning revealed multiple en- larged lymph nodes in the mediastinum and the largest of which under the tracheal protuber- ance was about 2.6cm in size. No obvious change. Pulmonary CT scanning revealed multiple enlarged lymph nodes in the mediastinum and the largest of which under the tracheal protuberance was about 1.0 cm in size. Table 1: Examination results at different time points of therapy.
  • 2. Copyright ©2018 Hou M. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. 2 Volume 1 Issue 1 -2018 Case Report Biopsy examination of a subcutaneous nodule of forearm re- vealed non-necrotizing epithelioid cell granulomas in the der- mis, epithelioid cells, giant cells and cellulose were observed. Special stains for acid-fast bacilli and fungi were negative. The histopathology of intrathoracic lymph nodes revealed epithelioid cell granulomas. Ophthalmological examination indicated the age-related macular degeneration which is not associated with sarcoidosis. Laboratory tests including peripheral blood routine, hepatorenal function, angiotensin-converting enzyme (ACE), and anti-nuclear antibody (ANA), serum calcium were all nor- mal. Tuberculin test was negative. The result of electrocardio- gram was normal. His superficial lymph nodes were not enlarged (Figure 1). Figure 1: Pulmonary CT revealed that the largest lymph node turned signifi- cantly smaller than before. Based upon the clinical and histopathologic findings described above, the patient was diagnosed with subcutaneous sarcoidosis with systemic involvement. Oral administration of tranilast 300 mg per day was begun. The skin became soft and nodules could not be touched (still could be detected by ultrasound). Moreover, the symptoms of chest pain, dry cough and dyspnea disappeared entirely after 3 months of therapy (Figure 2). Two year later, ultrasonic manifestations of bilateral forearms re- turned to normal. At the same time, chest CT and abdominal ul- trasound were reexamined and the lesions both become smaller than before. During these courses of treatment, no side-effect has been recognized and the patient continues taking tranilast 300mg per day. So far, the patient has been followed up. The patient was then treated with 40 mg methylprednisolone along with anticoagulants (warfarin, low molecular heparin) and an antiplatelet (aspirin), which led to a dramatic reduction in his peripheral blood eosinophilia (at the absolute count of 0.63×109/L) and clearance of his skin rash in the first week of treatment. Thus far, follow-up has been consistent. 5. Discussion Sarcoidosis is a systemic disease characterized by the presence of non-caseating epithelial granuloma involving multiple organs of the body. There have been some reports showing the effective- ness of tranilast in treating cutaneous lesions in some cases of granulomatous disorders such as granuloma annulare, and sar- coidosis [1,2]. It has been demonstrated that tranilast decreases adhesion molecules such as ICAM-1 and LFA-1 expression on monocytes, inhibits the release of chemical mediators and affects the monocyte macrophage-lineage cells, resulting in resolution of the granulomatous lesions [3]. The major mode of the drug’s efficacy appears to be the suppression of the expression and/or action of the TGF-β pathway, inhibiting collagen synthesis in fi- broblasts [4]. In this case, after the treatment of tranilast for 3 months, subcu- taneous nodules could not be touched and symptoms of chest pain, dry cough and dyspnea disappeared completely, which sug- gests that tranilast is effective in treating systemic sarcoidosis and may improve clinical symptoms after three months. After nearly two years, the ultrasonic findings of subcutaneous nodules disap- peared completely. But the manifestations of pulmonary lymph nodes and spleen, have not returned to normal. Treated with tra- nilast, subcutaneous nodules vanished ahead of internal organs, so it can be inferred that enlarged lymph nodes and spleen were as firm as subcutaneous nodules at the beginning but turned soft along with therapy, resulting in clinical remission. However, it takes a long time to observe all internal organs to return to nor- mal and the time is up to the range of involvement. Our patient still needs further follow-up observation. Whether it will relapse after stopping the medicine is still a question. There has been no report of sarcoidosis invovling several organs with systemic symptoms of fatigue and respiratory symptom treated successful- ly with tranilast. Although we report only a single case, tranilast may be a reasonable treatment option for not only cutaneous sar- Figure 2: Skin ultrasound indicated that after nearly 2 years of treatment, sub- cutaneous nodules returned to normal.
  • 3. United Prime Publications: http://unitedprimepub.com 3 Volume 1 Issue 1 -2018 Case Report coidosis but can relief other sarcoidosis symptoms. 6. Compliance with Ethical Standards Funding: This article was funded by Jiangsu Provincial Six Talent Peaks (2013-WSN-031) and Jiangsu Education Science 12th Five- Year programe (D/2013/01/015). 7. Conflict of Interest We declare that there is no conflict of interest. 8. Ethical approval This article does not contain any studies with animals performed by any of the authors. References 1. Nakahigashi K, Kabashima K, Akiyama H, Utani A, Miyachi Y. Re- fractory cutaneous lichenoid sarcoidosis treated with tranilast. JAAD. 2010:63(1):171-2. 2. Yamada H, Ide A, Sugiura M, Tajima S. Treatment of cutaneous sar- coidosis with tranilast. J Dermatol. 1995:22(2):149-52. 3. Mizuno K, Okamoto H, Horio T. Inhibitory influences of tranilast on multinucleated giant cell formation from monocytes by superna- tant of concanavalin A-stimulated mononuclear cells. J Dermatol Sci. 2000:24(3):166-70. 4. Yamada H, Tajima S, Nishikawa T, Murad S, Pinnell SR. Tranilast, a selective inhibitor of collagen synthesis in human skin fibroblasts. J Bio- chem. 1994:116(4):892-7.