Scleromyxedema in an adult following Sinopharm BBIBP-CorV vaccination: An extremely rare phenomenon

Abstract

Introduction:

The Sinopharm BBIBP-CorV vaccine produces a variety of cutaneous adverse effects. Scleromyxedema is a mucinous connective tissue disorder that causes skin thickness and sclerodermoid changes. According to our findings, this is the first case of scleromyxedema induced by the Sinopharm immunization.

Case description:

We discuss the case of a 75-year-old woman who acquired progressive thickening of the skin in her limbs and trunk after getting the Sinopharm vaccination. Examination, laboratory testing, and a biopsy were used to verify scleromyxedema diagnosis. Intravenous immunoglobulins, mycophenolate mofetil, and prednisolone were used in the treatment of the patient. The outcomes from the 4-month follow-up were reassuring.

Conclusion:

This study emphasizes the need of considering scleromyxedema as a connective tissue pathology in patients who have recently received Sinopharm vaccine and have similar cutaneous signs.

Introduction

Scleromyxedema is a mucinous connective tissue condition characterized by papular and sclerodermoid alterations, increased thickness, mucinous element deposition, and disorganized fibroblast proliferation in the skin layers. ¹ The condition affects middle-aged people of all genders. ¹ Extracutaneous manifestations might occur in the lungs, heart, gastrointestinal tract, and other organs. ¹ The cause of this disease has yet to be determined. ¹

According to the literature, the Sinopharm BBIBP-CorV vaccination causes various cutaneous side effects. ² According to our research, this is the first incidence of scleromyxedema caused by the Sinopharm vaccination. We present the case of a 75-year-old woman who developed gradual thickening of the skin in her limbs and trunk after receiving the Sinopharm vaccine. Scleromyxedema was diagnosed based on the examination, laboratory tests, and biopsy. The patient was treated with Intravenous immunoglobulins, mycophenolate mofetil and prednisolone. The 4 months follow-up showed promising results.

Case description

A 75-year-old female presented to the hospital clinic mentioned that 4 months before, after receiving the first vaccine shot with Sinopharm BIBP vaccine (BBIBP-CorV), she started to develop progressive dryness of her hands, feet and trunk, rigidity, and thickness of the skin. One month after vaccination, she was infected with COVID-19. Moreover, 2 months before her arrival, she had once been hospitalized due to pericardial effusion. Over the last 4 months, her skin symptoms started from lower limbs, gradually extending to the trunk and upper extremities. She did not complain about Reynaud’s phenomenon (Figure 1).

Figure 1.

Summary of clinical manifestations of scleromyxedema in our patient (Created with BioRender.com).

On her arrival, she was suffering from stiffness and mild swelling of fingers and toes. She did not receive any treatment for her skin symptoms. Her family history was negative for rheumatologic diseases. Initial assessment revealed blood pressure = 120/85 mm Hg, Temperature = 36.9 C, Heart rate = 69 bpm, and O₂ saturation = 97%. Our examinations revealed thickness and coarsening of skin in legs, trunk, and hands; sclerodactyly; hyperpigmentation of face and hands; and dryness of mouth and mucosa.We observed slight non-pitting edema in the arms and legs. The range of motion in upper and lower limbs was limited, and the skin rigidity was higher than normal. The flexion and extension of the wrists were painful.

Our baseline investigations include normal electrocardiogram, echocardiography that showed moderate pericardial effusion without hemodynamic effect. The spiral chest computed tomography was suggestive of the post-COVID-19 infection healing phase.

Laboratory investigations were negative COVID-19 test (RT-PCR), increased erythrocyte sedimentation rate (ESR 1 h = 81 mm/h) and C-reactive protein levels (CRP = 32.9 mg/L), normal white blood cells count (4900/µL), anemic hemoglobin levels (Hb = 10.5 g/dL), normal serum creatinine (Cr = 0.9 mg/dL), thyroid hormones within normal range, negative rheumatoid factor, normal CPK (95 U/L), negative antinuclear antibody (ANA), negative fluorescent antinuclear antibody (FANA), negative anti centromere antibody, negative anti SCL-70 antibody (topoisomerase), negative anti ds-DNA, negative anti-cyclic citrullinated peptides, and normal CH50 levels (All immunologic factors came back negative). The serum electrophoresis with immunofixation showed normal results.

The primary initial differential diagnosis included scleroderma and its mimics (scleromyxedema, scleroderma adultorum, eosinophilic fasciitis). Considering the site of development of skin symptoms and negative Raynaud’s phenomenon, a wedge-shaped biopsy was collected from her forearm to establish the diagnosis (Figure 2).

Figure 2.

A wedge-shaped biopsy from the patient’s forearm showed mucin deposits (arrow) in the hypoderm, fibrosis, and irregular fibroblast proliferation and an increase in collagen deposits (H&E color, 100×).

According to the specific site of skin changes (mostly lower limb and trunk) and the mucinous deposits in the hypoderm in the microscopic study of the biopsy, the negative Reynaud’s phenomenon, normal thyroid hormones, and negative immunologic factors, such as FANA, the diagnosis was consistent with scleromyxedema.

The patient underwent the scleromyxedema treatment protocol of our institute. Initially, she was treated with intravenous immunoglobulins (IVIG), prednisolone 0.5 mg per kg daily and mycophenolate mofetil 2 g per day. Over the next 3 months, the IVIG was continued monthly, the prednisolone was tapered gradually. She was satisfied with the treatment progress, and her skin thickness symptoms showed improvements. She experienced no unsatisfactory or unanticipated events. However, patient follow-up is required for longer periods in terms of no recurrence.

Conclusion

Scleromyxedema is an extremely rare disease with high morbidity and mortality. Although it has been recognized since 1900, there is no estimation of prevalence and incidence rates. The diagnostic approach proposes the following features: papular cutaneous eruption; skin biopsy, which is the cardinal feature of the disease; existence of monoclonal gammopathy on a blood sample; and absence of thyroid dysfunction.^3,4 Although the etiology is unknown, the fibroblast is the possible factor in the pathophysiology of the disease. The first-line treatment for scleromyxedema is IVIG and subsequent systemic glucocorticoid therapy. ⁵ The prognosis is not well established, but there is high morbidity and mortality rate.

The vaccine was urgently needed due to the coronavirus epidemic. According to a phase 1/2 trial of the Sinopharm vaccine as an inactivated whole virus vaccine, it causes 1%–10% local cutaneous symptoms including erythema, edema, and increased induration, as well as less common (1%) abnormalities like rash or itching.^2,6 Of course, the occurrence of cardiac manifestations such as pericarditis and pericardial effusion, secondary to COVID vaccination, is probably because the vaccine triggers the immune system, is not new and can justify the patient’s previous hospitalization for heart problems.^7,8

Based on our search in the literature, the scleroderma-like adverse reactions after the Sinopharm vaccine has not been reported yet. Mucin deposition and fibroblast proliferation, as well as a collection of extracellular fibrotic changes, characterize scleromyxedema.

According to Niebel et al., ² these types of reactions are classified as foreign body extracellular responses. T-cell dysregulation, interleukin 10 and tumor growth factor beta production, enhanced macrophage-mediated granulomatous responses, elongated inflammatory activity, and cutaneous fibrosis are all triggered by vaccine-induced trauma and extracellular matrix disintegration following injection. ² These potential mechanisms, however, appear to have a role in localized responses. It is worth noting that there is a scarcity of information in the literature on the various processes that might cause same cutaneous symptoms.

Numerous cases of sclerosis and morphea, secondary to influenza and hepatitis vaccination, have been reported, which may partly confirm the cause of the complication in our case, which of course were very rare.^9,10 In other words, our report is important because of a new case study of the effects of immune system induction on the dermis and the development of secondary sclerotic effects to coronavirus vaccination. Our case study highlights scleromyxedema as a potential side effect of the BBIBP-CorV (Sinopharm) vaccination. This information will help physicians consider the vaccine history and perform the diagnostic approach to diagnose scleromyxedema-like lesions. Physicians require a high level of clinical knowledge to rule out other sclerotic rheumatologic disorders. In addition to other diagnostic criteria, a biopsy is required to begin appropriate treatment.