Multiple subcutaneous haematomas of the legs causing skin necrosis in an elderly patient affected by corticosteroid‐induced skin atrophy: Case report and review of literature

Abstract

Corticosteroid‐induced skin atrophy (CISA) consists of a thinning of the skin and subcutaneous tissues, representing the natural consequence of a prolonged glucocorticosteroids use, both systemic as well as topical. It is characterised by the loss of elasticity and skin thickness, associated with an increased skin fragility leading to ecchymoses, haematomas, and steroid purpura. The management of CISA is a challenge for physicians, as the pathology is reversible in a minimal percentage of cases and only after a short topical steroid or low‐dose course therapy. Often wounds with large loss of substance represent the more common complication, after a surgical drainage which is often necessary. Skin necrosis with compartment syndrome of a leg is another potential risk for these patients. Here, we report a case of an elderly patient affected by multiple subcutaneous haematomas of the legs causing skin necrosis, arisen after the use of anticoagulants for a deep venous thrombosis. The patient was successfully treated with surgical drainage, negative pressure wound therapy (NPWT), and porcine xenograft with no complications. Finally, we discuss the evidence of the current literature on topic.

1. INTRODUCTION

Corticosteroid‐induced skin atrophy (CISA) consists of a thinning of the skin and subcutaneous tissues, representing the natural consequence of a prolonged glucocorticosteroids (GCs) use, both systemic as well as topical. More rarely the disease has been associated with high doses of inhaled corticosteroids.1, 2

The disease was first observed in 1950 by Castor and Baker,3 which observed a dermal thinning in the skin of rats after topical hydrocortisone application. In 1963, Epstein and coworkers4 made the original description of the disease, reporting five male patients with atrophic striae in the groins who received a topical steroid therapy.

1.1. Pathogenesis

Both systemic5, 6 as well as topical steroidal therapies7, 8, 9 can induce dermal atrophy, because of their catabolic effects on protein metabolism. A single application of topical steroid can produce an ultrasonographically detectable decrease in skin thickness more evident up to 3 days10 but the effects can be reversible during low‐dose or periodic steroidal treatment.2, 11

Cushing's syndrome is also closely linked to CISA, being cortisol excess responsible of a generalised dermal thinning and of the development of violaceous striae, most common around the sides and lower abdomen.12

GCs mechanism of action is mediated by the GC receptor (GR) binding, which lead to changes in gene expression.13 Upon glucocorticoid binding, GR undergoes phosphorylation, dimerization, and translocates to the nucleus, where it regulates gene expression positively (transactivation) or negatively (trans‐repression).14 A role of mineralocorticoid receptor (MR) is also called into question, because topical MR blockade could limit glucocorticoid‐induced epidermal atrophy.15

Although molecular steroid‐induced atrophy mechanisms have not yet been fully understood, it is known that expression of the HA synthesising enzymes hyaluronan synthase (HAS)‐2 was markedly suppressed by dexamethasone treatment of cultured fibroblasts.16

Besides this, the binding to the GR stimulates the phospholipase C/protein kinase C signalling system, with inhibition of glycogen synthase kinase 3b, leading to the activation of b‐catenin and c‐myc, biomarkers of impaired tissue reparation.17

Recently, it has also been discovered that one of the GR target genes in skin‐regulated in development and DNA damage responses 1 (REDD1) is involved in steroid atrophy.18

The atrophogenic potential of each steroid depends on several factors including its potency,19 duration of therapy,20 frequency of application,21, 22 skin phototype,23, 24 and further unknown factors.

1.2. Histopathology

The histologic findings of CISA include decreased number and size of epidermal keratinocytes with a faster rate of maturation in vivo,25 flat dermal–epidermal junctions,26 reduced collagen 127 and 328 synthesis in the dermis, reduced production of fibroblasts29, 30 and hyaluronic acid,31, 32 and reduction of the intercellular lipid layers,33 resulting in a disarray of the extracellular matrix. Inhibition of the function of melanocytes may also occur, resulting in a localised loss of pigmentation.5

1.3. Clinical features and diagnosis

Systemic steroids, taken for a long period or chronically, induce several adverse effects such as diabetes, cushingoid appearance, osteoporosis, glaucoma, and peptic ulcers. The most important cutaneous side effect is generalised skin atrophy, characterised by a cigarette paper‐like consistency.

Concerning the topical GCs administration, the most common areas involved are those where the dermis thickness is particularly thin and more sensitive to GCs penetration, such as the face, genitals, and intertriginous areas of the groin and axilla.

The diagnosis is essentially clinical, as skin biopsy is not recommended because of the high risk of creating non‐healing wounds or infections.

CISA is characterised by loss of elasticity34 and skin thickness, associated with an increased fragility involving both the skin and the capillaries. The latter condition, more relevantly for patients in anticoagulant therapy, can lead to ecchymoses, haematomas, and steroid purpura,35 being dermal vessels more superficial and subjected to minor trauma. Telangiectasias are also commonly found,36 because of nitric oxide release from dermal vessel endothelial cells leading to abnormal dilatation of capillaries.37

1.4. Differential diagnosis

A variety of other diseases may enter the differential diagnosis, such as senile skin atrophy,38 hydroxyurea dermopathy,39 striae distensae,40 rheumatoid disease,41 lichen sclerosus et atrophicus,42, 43 atrophoderma vermiculatum,44 atrophoderma of Pasini and Pierini,45 linear atrophoderma of Moulin,46 Gowers local panatrophy,47 acquired poichiloderma,48 atrophying pityriasis versicolor,49 and Lyme disease.50

1.5. Treatment

The management of CISA is a challenge for physicians, as the pathology is reversible in a minimal percentage of cases and only after a short topical steroid or low‐dose course therapy. Thus, the first treatment is steroid discontinuation. However, while telangectasias may improve marginally, striae are permanent and irreversible.

Protection and support of the damaged skin barrier is another important priority. Currently, a number of topical products containing ceramides, hyaluronic acid, licorice extracts, dimethicone, petrolatum, colloidal oatmeal, and paraffin wax have demonstrated efficacy as barrier repair creams.51, 52

1.6. Case report

A 93‐year‐old female was admitted in our ward for edema and left lower limb pain for which she was sent by the G.P. to do a venous ultrasound scan. Past medical history included previous cholecystectomy and uterine myomectomy, hypertension in treatment with Ace inhibitors, COPD in chronic steroid therapy both inhaled and often systemically administered because of recurrent infections of the upper respiratory tract and chronic venous insufficiency.

The compression ultrasonography detected an anechoic thrombus with a non‐compressible venous segment from the third proximal left femoral vein, distally extended, with partial occlusion of the popliteal vein. Electrocardiogram showed a not datable atrial fibrillation with normal ventricular response.

The patient started anticoagulant therapy with fondaparinux 7,5 mg once daily, to be continued for at least 3 months. The following day the patient developed a painful left pretibial hematoma, with initial cellulite's signs and superficial skin ulcerations for which antibiotic management with piperacillin/tazobactam was initiated. On the third day of hospitalisation, the hematoma was surgically removed and it was applied NPWT at a pressure of 125 mm Hg on a continuous setting. After 7 days of treatment, she was discharged and she continued NPWT as home therapy for 2 weeks; the antibiotic treatment was discontinued after a 7 days course therapy. Afterwards, she was treated with hyaluronic acid granule dressings with an overlying secondary application of polyurethanic non‐adherent foam. A zinc paste bandage was applied and changed every 5 days having consecutive accesses as outpatient in our II level Wound Healing ambulatory. In a total of 52 days, the ulcer was completely healed (Figure 1).

Figure 1.

Hematoma of left leg surgically drained and consequent wound healed with NPWT in 52 days

Some days later, after a mild grip movement done by her caregiver, the patient developed a contralateral deeper hematoma of the calf, which rapidly evolved into necrosis consequent to an acute compartment syndrome (Figure 2). The fondaparinux dose was at this time reduced to 5 mg once daily.

Figure 2.

Calf necrosis as a consequence of compartment syndrome

The patient underwent a new surgical intervention, with removal of all necrotic tissues and blood clots overlying the soleus muscular fascia. In the operating theatre, it was immediately applied NPWT that she continued for 5 weeks. The NPWT kit was changed in our ambulatory every week. At the fifth week of treatment, the bottom of the lesion was significantly increased and showed signs of advanced granulation with no bacterial colonisation or contamination. The wound was treated with EZ Derm® application (Molnlycke Health Care, US, LLC, Norcross, GA), an off‐the‐shelf porcine xenograft that has been shown to reduce pain, be cost‐effective, and provide an environment conducive to wound healing.53 In order to avoid further risks for the atrophic skin, the graft was not been sutured but simply fixed with surgical tape strips (Figure 3).

Figure 3.

Porcine xenograft fixed on the atrophic periwound with surgical tape strips

Then, it was used as overlying secondary dressing Cutimed Sorbact gel® (BSN Medical, UK, Willerby, Hull), a hydrogel‐impregnated dressing coated with a hydrophobic fatty acid that irreversibly binds to the bacterial surface and mechanically removes bacteria from the wound (Figure 4).54 Finally, a polyurethane foam was applied as third dressing, to manage the exudation. A zinc paste bandage was applied and changed every 5 days. In a total of 28 days, the xenograft was definitely incorporated leading to almost complete wound healing (Figures 5 and 6). No antibiotics were administered during the whole period up to the healing.

Figure 4.

Hydrogel‐impregnated dressing coated with a hydrophobic fatty acid applied on the porcine xenograft

Figure 5.

Wound incorporation of porcine xenograft after 7 days

Figure 6.

Wound appearance after 28 days from the xenograft application

The use of LWM heparin and other oral anticoagulants was finally abandoned, considering the high risk of subcutaneous hematomas.

2. DISCUSSION

From a critical review of medical literature on topic, we found that CISA's pathogenetic mechanisms are quite well known in vitro but poorly analysed from a clinical and practical point of view, especially in relation to the onset of deep subcutaneous hematomas closely linked to anticoagulant therapy.

In the guidelines for stroke prevention in patients with atrial fibrillation, the risk of major bleeding given by the anticoagulants use is identified by a score and is defined as being intracranial bleedings, hospitalisation, haemoglobin decrease >2 g/dL, and/or transfusion.55

However, the specific problem of the risk of developing deep subcutaneous hematomas in general and more specifically in patients affected by CISA is never mentioned. In particular, the risk of evolution in compartment syndrome with necrosis of the cutaneous tissues and of the deeper structures is not considered, which as regards the limbs, can lead to gangrene and high risk of major amputations.

Thus, the decision of administrating anticoagulant therapy is mainly based on a scored‐balance between bleeding and clotting, being bleedings substantially considered as intracranial or gastrointestinal ones. Nevertheless, a moderate bleeding in a closed compartment as a limb cannot easily meet the score criteria already mentioned, leading anyway to several damages for the patient, including major amputation and even risk of death.

Other unresolved issues relate to the type of drug used for anticoagulation and whether the dosage should be reduced in the patient with CISA or not. In the specific case‐report, we only note that elimination half‐life of fondaparinux is the highest between the available LMWH, being approximately 17 hours in healthy young subjects and 21 hours in healthy elderly subjects, versus approximately 4 hours for the others.56

In relation to the advanced dressings and skin grafts used to promote tissue repair in CISA patients, there are no clinical studies able to highlight the superiority of one dressing over another. In our experience, the use of negative pressure appeared to be effective and well tolerated by the patient, who presented a post‐surgical lesion with a wide loss of substance. The use of the porcine xenograft almost immediately allowed the resolution of pain and the cessation of painkillers drugs, improving patient's quality of life.

The success of a skin graft transplantation depends on the management of exudate and local bacterial burden57: in our case, we have chosen to use of Cutimed Sorbact gel®, which allowed a good bacterial load control through a physical mechanism, therefore not locally harmful for tissue repair. Besides, this it has allowed to maintain the right local wet environment through a hydrogel slow‐release mechanism. The overlying polyurethane foam, despite losing some of its absorbing capacity under bandage, appeared to be important for the absorption of the excess of exudate and prevented the periwound skin maceration.

The last open issues are how to prevent hematoma and/or ulcers recurrences and which kind of protection can be effective for this purpose. No solid data are available on this topic. In our experience, on the atrophic not ulcerated skin, we have successfully used a cream barrier, composed by omental lipids and enhanced by the synergistic activity of vitamin A, vitamin E, allantoin, and hyaluronic acid; skin protection was achieved through a three layers anelastic bandage, renewed every 5–7 days.

We do not consider safe the use of compression stockings, because of the risk of producing tear injuries on the atrophic skin while positioning and wearing them. An acceptable option for the maintenance and prevention, in order to avoid protracted hand‐made bandages which necessarily need expert operators and thus representing a significant cost, could be the use of an off‐the‐shelf adjustable compression system which does not need high expertise and it is quite simple to apply, once tailored on the patient's leg.

3. CONCLUSIONS

CISA is a frequent, complex, and underrated pathology that is often not reversible and subjected to evolve in multiple skin ulcerations. The management of a wound in CISA is not substantially different from the other wounds but a particular protection of the periwound skin, through the use of fat cream barriers, is recommended.

In our experience, NPWT has shown to be effective, accelerating healing and reducing both pain and risk of infection. The use of a xenograft seemed also to be a good option, because the autograft is not a suitable option for these patients. The most important issues for its successful incorporation on the wound were the exudate and bacterial management, achieved with specific dressings and with anelastic bandage, avoiding to fix it with stitches.

Although there are no solid data about the use of anticoagulants in CISA patients, we think that the decision of administering them, especially in the elderly patients, need an extensive evaluation, not only taking into consideration major bleedings but also the concomitant risk of developing deep subcutaneous hematomas, potentially evolving in skin necrosis and compartment syndrome of the legs.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

Vallini V, Rinaldi E, Mangano L, et al. Multiple subcutaneous haematomas of the legs causing skin necrosis in an elderly patient affected by corticosteroid‐induced skin atrophy: Case report and review of literature. Int Wound J. 2020;17:540–546. 10.1111/iwj.13312