Pachydermoperiostosis Associated with Myelofibrosis: A Rare Case Report.

Sir,

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 1a], cutis verticis gyrata [Figure 1b], 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)

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 1c]. 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 2b, d and 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)

Bone marrow biopsy findings included atypical megakaryocytes (hyperchromatic and hypolobated) in addition to increased reticular fibers and collagen accumulation compatible with MF [Figure 2a and 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 3a and b], and doxycycline (100 mg every 12 h) for 6 months was given [Figure 3c]. 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 3d]. 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

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.[45] 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.[78] 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.

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Conflicts of interest

There are no conflicts of interest.