Morphea after Borrelia-induced facial nerve palsy

Abstract

Morphea, also known as localized scleroderma, is characterized by inflammation and fibrosis of the skin. The exact pathogenesis of morphea is unknown, but generally includes genetic predisposition to autoimmunity combined with an environmental insult. Previous cases have been associated with active Borrelia infection; however, Borrelia infection as a direct cause of morphea was not generalizable to most patients. Within endemic areas, Borrelia burgdorferi is the most common cause of facial nerve paralysis, another autoimmune phenomenon. We report a case of facial morphea in a young man with family history of autoimmune disease who developed morphea in the same location as two previous episodes of Borrelia-induced facial nerve palsy. This case is remarkable because it suggests Borrelia burgdorferi induced loss of local immune tolerance to host antigens, first with facial nerve palsy and followed years later by development of morphea.

Introduction

Morphea, also called localized scleroderma, is an immune mediated fibrotic disorder of the skin that most commonly occurs in a circumscribed or linear distribution and may extend to subcutaneous structures. The exact etiology of morphea is unclear but likely multifactorial, involving an environmental or local trigger, such as trauma, radiation, medications, and infection, in combination with an autoimmune genetic predisposition. ¹ Concurrent or prior Borrelia infection has previously been associated with development of morphea,^{2 –4} but serological examination suggests that it is not a trigger in most patients. ⁵ Some of this discrepancy may be influenced by geographic variation of Borrelia species, where Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii are pathogenic to humans in Europe, but B. burgdorferi sensu stricto is the sole pathogenic species in the United States. ⁶ Neuroborreliosis has also been associated with the development of different types of morphea, including one patient who developed a patch of morphea on the neck 20 years after left-sided facial palsy. ⁷ We present a case of morphea after Borrelia-induced facial nerve palsy and discuss the immunologic implications.

Case report

A 21-year-old man from northeastern Connecticut presented June 2019 with left-sided facial atrophy and jaw pain that started 1.5 years earlier. In 2004 and 2014, he had two episodes of acute left-sided facial paralysis with associated malaise attributed to Lyme disease with two positive B. burgdorferi immunoglobulin M (IgM) bands on immunoblot. He otherwise had no fever, headache, arthralgia, or skin rash. The facial palsy improved with a 3-week course of doxycycline, but he had persistent left upper eyelid elevation requiring lubricating drops (Figure 1, left). In 2015, he fell from a roof and hit his left face in a similar location as the inferior atrophic area. He had no history of herpetic lesions, Raynaud phenomenon, or other neurologic deficits. His family history was notable for maternal aunts with lupus and psoriasis and maternal grandmother with rheumatoid arthritis. His facial lesions were previously treated with high potency topical steroids without improvement.

Figure 1.

Left-sided facial morphea in a patient with history of multiple episodes of Borrelia-induced facial nerve palsy. Head-on and left cheek photos after completing methotrexate for 4 months and one round of methylprednisolone infusions. Head-on photo shows left upper eyelid elevation from weakness of the facial nerve, which is responsible for closing the eyelids, and lack of hemifacial atrophy. Left cheek photo demonstrates two sclerotic plaques with associated lipoatrophy, outlined with dashed ovals. Scar from skin biopsy is located along the left jawline.

On examination, the left lateral cheek had two sclerotic nontender plaques measuring 8.5 and 2.5 cm with associated lipoatrophy and peripheral erythema (Figure 1, right). His left upper eyelid was asymmetrically elevated consistent with persistent facial nerve weakness (Figure 1, left). No marked facial atrophy, sclerodactyly, nailfold dystrophy, or dilated vessels were noted. Based on the examination, we favored a diagnosis of circumscribed morphea.

Skin biopsy from the left cheek revealed a patchy perineurovascular infiltrate of lymphocytes and plasma cells (Figure 2). Neither vasculitis nor endothelial reactive changes were evident. There were thickened collagen bundles throughout the dermis with diminished intercollagenous fenestrations. Adnexal structures were scant and periadnexal fat was not seen. A Fite’s acid fast stain was negative for micro-organisms. Additional workup demonstrated anti-nuclear antibody (ANA) 1:640, four positive B. burgdorferi immunoglobulin G (IgG) bands by immunoblot, negative Treponema pallidum antibody, and magnetic resonance imaging (MRI) of the head without enhancing lesions.

Figure 2.

Skin biopsy from the left cheek. Hematoxylin and eosin staining shows a patchy perivascular lymphoplasmacytic infiltrate with thickened collagen bundles and diminished intercollagenous clefting. Adnexal structures are diminished. Inset shows parallel neural (arrow) and vascular structures with surrounding lymphocytes and plasma cells (magnification, ×40 and inset magnification, ×200).

For treatment of morphea, he completed 4 months of methotrexate and three monthly infusions of pulse methylprednisolone per consensus recommendations. ⁸ Photos of his face after treatment with methotrexate and one round of methylprednisolone infusions are shown in Figure 1. Methotrexate was stopped early by the patient due to fatigue and nausea and he was not amenable to subcutaneous administration. He experienced improvement in his jaw pain after starting methylprednisolone, which he had commenced during the last month he took methotrexate. Treatment overall resulted in stabilization of the sclerotic plaques and reduced their erythema.

Conclusion

We report a case of circumscribed morphea occurring on the face in the same distribution as Borrelia-induced facial nerve palsy. Diagnostically, his clinical examination overlaps with Parry–Romberg syndrome (PRS), a rare subtype of localized scleroderma that causes hemifacial atrophy. Progressive hemifacial atrophy is a defining feature of PRS and is accompanied with overlying sclerosis in 53%–71% of patients.^9–11 In those patients with sclerosis, cutaneous induration was observed to precede tissue atrophy, ¹¹ so our patient may also be considered in the spectrum of early PRS prior to the development of hemifacial atrophy. Another diagnostic consideration is lupus panniculitis, which may also occur on the face, and involves inflammation of the fat that leads to indurated plaques. Morphea can cause septal panniculitis in some cases; however, the presence of dermal fibrosis and absence of panniculitis or overlying discoid lesions distinguishes this case from lupus. Altogether these findings highlight some of the heterogeneity in clinical presentation of morphea, and the temporal relationship between sclerosis and atrophy in PRS.

B. burgdorferi infection is the most common cause of facial nerve palsy in children of endemic areas (as in our patient) in the United States and despite treatment with antibiotics, facial nerve palsy can last months after treatment is completed. ¹² This suggests that Borrelia-induced facial nerve palsy involves a localized loss of immune tolerance to host antigens that results in damage to the facial nerve. Furthermore, anti-Borrelia antibodies can cross-react with neural antigens ¹³ and in chronic neuroborreliosis, cross-reactive T cells have been identified that bind multiple host-derived antigens including transforming growth factor beta-3 (TGFβ-3) and interleukin-1 (IL-1) receptor. ¹⁴

B. burgdorferi infection as a direct cause of morphea has been controversial and not supported by larger studies. ⁵ However, Borrelia-associated morphea may represent a post-infectious sequela resulting from infection-induced autoimmunity. Our patient was infected multiple times with B. burgdorferi causing a local reaction to his facial nerve. This reaction may have been exacerbated by additional traumatic jaw injury at the site of one of the lesions, but a second discrete lesion on his zygoma (left upper cheek) suggests not simply a physical traumatic etiology. Onset of morphea can occur years after a sensitizing event such as after radiation exposure. ¹⁵ We suggest that a similar loss of immune tolerance to host antigens occurred in our patient, first against his facial nerve, and subsequently to additional antigens to cause localized scleroderma. While there is extensive literature regarding the role of Borrelia infection in the development of morphea, this case is unique in that it associates with a second local autoimmune phenomenon as a direct consequence of Borrelia infection prior to the development of morphea.