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Year : 2019  |  Volume : 64  |  Issue : 6  |  Page : 501-503
Pachydermoperiostosis Associated with Myelofibrosis: A Rare Case Report

1 Department of Dermatology, Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
2 Department of Pathology, Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
3 Department of Hematology, Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
4 Department of Ophtalmology, Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Date of Web Publication7-Nov-2019

Correspondence Address:
Nurimar C Fernandes
Department of Dermatology, Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijd.IJD_360_18

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How to cite this article:
Secchin P, Fernandes NC, Quintella DC, R Silva JA, Medrado J, Magalhães TC. Pachydermoperiostosis Associated with Myelofibrosis: A Rare Case Report. Indian J Dermatol 2019;64:501-3

How to cite this URL:
Secchin P, Fernandes NC, Quintella DC, R Silva JA, Medrado J, Magalhães TC. Pachydermoperiostosis Associated with Myelofibrosis: A Rare Case Report. Indian J Dermatol [serial online] 2019 [cited 2023 Jan 29];64:501-3. Available from:


Pachydermoperiostosis (PDP) was described in 1868 as a hereditary disease caused by an abnormal proliferation of skin and bones, resulting in pachydermia, periostosis, and digital clubbing. Other abnormalities include cutis verticis gyrata, seborrhea/acne, palmoplantar hyperhidrosis, and bilateral blepharoptosis.[1]

A 25-year-old male patient presented with wrinkles on his face and arthralgia since adolescence. No familial similar condition was reported. Abnormal thickness of skin, facial wrinkles, seborrhea [Figure 1]a, cutis verticis gyrata

[Figure 1]b, bilateral blepharoptosis, finger clubbing, palmar/plantar hyperhidrosis, articular knee edema, and hepatosplenomegaly were noticed.
Figure 1: (a) Cutaneous increased thickness and facial wrinkles, (b) Cutis verticis gyrata at occipital region, (c) Tibia's cortical increased thickness and periosteal reaction (arrow)

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Laboratory tests demonstrated normochromic and normocytic anemia (hemoglobin 7 g/ml), thrombocytopenia (platelet count 93,000/ml), serum cyanocobalamin level was 182 pg/ml (normal 193–982 pg/ml); plasma prostaglandin E2 (PGE2) (1342.0 pg/ml; normal 340–428 pg/ml) and urinary PGE2 (more than 15007.5 pg/min; normal 173–573 pg/min) elevation. Blood smear showed anisopoikilocytosis, teardrop-shaped red blood cells. VDRL test and TPHA test were negative.

X-ray revealed cortical thickening and irregular periosteal reaction of tibia and femur [Figure 1]c. A skin biopsy of the frontal region revealed increased thickness of dermis, fibrosis, sebaceous hyperplasia, discrete accumulation of dermic mucopolysaccharides, as well as reduction of elastic fibers [Figure 2]b, [Figure 2]d and [Figure 2]e.
Figure 2: (a) Bone marrow fibrosis (H and E, ×10). (b) Skin biopsy showing increased thickness of the dermis, fibrosis, and sebaceous glands hyperplasia (H and E,×2.5). (c) Bone marrow fibrosis (Masson's trichrome,×10) (d) Dermal acid mucopolysaccharides slightly increased (Colloidal iron stain,×10). (e) Elastic fibers focally reduced (Orcein ×10)

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Bone marrow biopsy findings included atypical megakaryocytes (hyperchromatic and hypolobated) in addition to increased reticular fibers and collagen accumulation compatible with MF [Figure 2]a and [Figure 2]c. Mutation studies on exon 14 of gene JAK-2 came out negative, and the empiric addition of parenteral cyanocobalamin was ineffective, with no improvement in blood cell count.

Two peelings were done with retinoic acid 7%, a tunneling, and shaving of the tuberous wounds on malar and front regions [Figure 3]a and [Figure 3]b, and doxycycline (100 mg every 12 h) for 6 months was given [Figure 3]c. Bilateral blepharoptosis compromised eye function. The reinsertion of aponeurosis on upper eyelid lifting muscle (UELM) on the superior part of the eyelids, associated with a narrowing of the eyelid plaque, was performed [Figure 3]d. The eyelid plaque was rebuilt through anchorage sutures between skin/orbicular and the aponeurosis of the UELM.
Figure 3: (a) Cutaneous increased thickness and facial wrinkles. (b) Shaving of tuberous wounds at malar region. (c) Six months after the initial treatment. (d) Blepharoptosis correction transcutaneously

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PDP is a rare, hereditary syndrome which is more common among men since puberty and progressing through adult life, i.e., after 5 to 20 years.[1]

According to some studies, the increase of PGE2 in patients with mutations in HPGD and SLCO2A1 genes could be involved in PDP pathogenesis. The SLCO2A1 gene codifies the PGE2 transport protein, which acts in the plasmatic membrane by selective absorption.[2] It has been discovered for the SLCO2A1 gene more than 40 pathogenic variants with variable expressivity of clinical manifestations.[3] On the other hand, HPGD gene codifies the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) main enzyme with activity in prostaglandin decay inside a cell.[4] Consequently, the mutation of SLCO2A1 and HPGD genes will lead to an increase in PGE2 levels by remodeling tissues and vascular stimulation, contributing to clinical manifestations.[4],[5] The patient's elevated urinary and plasmatic PGE2 prove this theory. Chronically elevated levels of PGE2 could stimulate osteoblasts and osteoclasts activity leading to prolonged local vasodilation, periostosis, acro-osteolysis, and digital clubbing.[1]

PDP diagnosis is based on clinical and radiologic findings whose phenotypic spectrum is wide.[1] Histopathological findings include increased thickness of dermis. No efficient treatment is available.[1] Isotretinoin inhibits sebaceous secretion, reduces keratinization, and fibroblasts action; therefore, enhancing skin's thickness and relieving acne. To control arthralgia and arthritis, non-steroidal anti-inflammatory, corticosteroids, tricyclic antidepressants, colchicine, and tamoxifen citrate can be used. Bisphosphonates would avoid bone remodeling. Infliximab for refractory arthritis has also been reported.[6]

The PDP-corresponding MF is a severe complication and, if neglected, could lead to death by refractory anemia. This association is rare according to 23 previous reports.[7],[8] Vascular endothelial growth factor, hepatocyte growth factor, platelet-derived and the lack of regulation of PGE2 probably trigger the proliferation of fibroblasts and collagen deposition.[7] Treatment of this secondary MF has no consensus, with few reports of improvement of anemia and some of the fibrosis findings in bone marrow with corticotherapy (prednisolone, 0.5 mg/kg/day).[9] Other options include transfusion of blood components and erythropoiesis-stimulating agents, however, conservative treatment was chosen due to lack of symptoms.

To enhance facial esthetics, the few existing reports prioritize blepharoplasty, resection of the eyelid, or reinsertion of aponeurosis of UELM. Other surgical techniques have been used such as frontal rhytidoplasty and facelift, which is recommended based on the specific circumstances of different individuals.[10] Botulinum toxin can bring temporary results.

The reported case presents PDP's complete form in association with MF. It is essential to stress on the importance of screening the comorbidities of this genodermatosis. As the patient was asymptomatic for MF and the main complaint was esthetic only, blepharoptosis corrections were performed allowing the rescue of self-esteem.

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.


The head of Dermatology Service at HUCFF-UFRJ, PhD Prof Marcia Ramos-e-Silva, for allowing prostaglandin examination.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola B. Pachydermoperiostosis: An update. Clin Genet 2005;68:477-86.  Back to cited text no. 1
Zhang Z, He JW, Fu WZ, Zhang CQ, Zhang ZL. Two novel mutations in the SLCO2A1 gene in a Chinese patient with primary hypertrophic osteoarthropathy. Gene 2014;534:421-3.  Back to cited text no. 2
Villarreal-Martínez A, Vázquez-Martínez OT, Martínez-de-Villarreal LE, Garay-Mendoza D, Rodríguez-Vivian C, Ocampo-Candiani J, et al.Primary hypertrophic osteoarthropathy: Report of two novel genetic variants in the SLCO2A1 gene in two Mexican patients.Indian J Dermatol Venereol Leprol 2018;84:446-7.  Back to cited text no. 3
[PUBMED]  [Full text]  
Uppal S, Diggle CP, Carr IM, Fishwick CW, Ahmed M, Ibrahim GH, et al. Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nat Genet 2008;40:789-93.  Back to cited text no. 4
Diggle CP, Parry DA, Logan CV, Laissue P, Rivera C, Restrepo CM, et al. Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis. Hum Mutat 2012;33:1175-81.  Back to cited text no. 5
da Costa F, Fialho S, Zimmermann A, Neves F, Castro G, Pereira I. Infliximab treatment in pachydermoperiostosis: A rare disease without an effective therapeutic option. J Clin Rheumatol 2010;16:183-4.  Back to cited text no. 6
Li S, Li Q, Wang Q, Chen D, Li J. Primary hypertrophic osteoarthropathy with myelofibrosis and anemia: A case report and review of literature. Int J Clin Exp Med 2015;8:1467-71.  Back to cited text no. 7
de Risi-Pugliese T, Danière F, Legrand L, Bancel P, Oppenheim C, Wipff J. Extramedullary hematopoiesis with spinal cord compression in pachydermoperiostosis. J Bone Spine 2017;84:509-51.  Back to cited text no. 8
Ninomiya S, Hara T, Tsurumi H, Kanemura N, Kasahara S, Ogawa Y, et al. Myelofibrosis successfully treated with prednisolone in a patient with pachydermoperiostosis. Intern Med 2011;50:2207-11.  Back to cited text no. 9
Taichao D, Fuling L, Hengguang Z. Comprehensive surgical strategies for the management of pachydermoperiostosis. Facial Plast Surg 2018;34:330-4.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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