Hansen's disease with McCune-Albright syndrome.

McCune-Albright syndrome (MAS) comprises a triad of fibrous dysplasia of bone, café-au-lait macule, and endocrinopathy. The disease is due to activating mutation of G protein-coupled receptor leading to hyperfunction of glands. Hansen's disease is caused by infection with Mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. We recently encountered a patient with Hansen's disease along with underlying MAS and report the same in this report.

INTRODUCTION

Fibrous dysplasia of bone is characterized by the replacement of medullary bone with fibro-osseous tissue. This results in the distortion and overgrowth of bone, leading to characteristic deformities.[1] Based on the bony involvement, fibrous dysplasia is divided into three types: monostotic, polyostotic, and McCune–Albright syndrome (MAS). MAS is characterized by a triad of monostotic/polyostotic fibrous dysplasia, cafι-au-lait macules (CALMs), and endocrine hyperfunction. The disease is congenital but not hereditary and is due to an activating mutation in G protein-coupled receptor.[2] It manifests usually in childhood, with recurrent fractures, distorted bones, precocious puberty, acromegaly, or hyperthyroidism.

Hansen's disease is a chronic infectious disease caused by infection with Mycobacterium leprae. The lesions typically involve the skin, mucous membranes, and peripheral nerves. Untreated disease leads to permanent disfigurement, and the disease is classified as paucibacillary or multibacillary depending on the proliferation of the bacilli.[3] The disease spreads by close personal contact through respiratory droplets. The risk factors for the disease are living in endemic areas with poor hygiene conditions and defects in cell-mediated immunity.[4] MAS predisposes to endocrine hyperfunction syndromes, but infectious diseases are not reported earlier. We recently encountered a patient with MAS who presented with cutaneous features of Hansen's disease. We report the same for the unusual association and to highlight the relevant review of the literature.

CASE REPORT

A 30-year-old man presented with hypoesthetic, depigmented patches over the skin of the chest and back of 1 year duration. He gave history of recurrent fractures since the age of 4 years with shortening of right leg. The parents gave history of hyperpigmented macules over the trunk since birth and denied similar features in family members. The patient attained puberty at the age of 14 years and denies history suggestive of acral enlargement, thyrotoxicosis, Cushing's syndrome, and swellings in any part of the body. Examination revealed (height 152 cm) asymmetry of the face with expansion of right maxilla and lower jaw and short right leg (82 vs 86 cm) [Figures 1 and 2]. Cutaneous examination revealed a large CALM over the back, extending across the midline and multiple anesthetic patches over scapula and lower back [Figure 3]. There was no evidence of goiter, acromegaloid features, and thickened nerves, and the rest of the examination was normal.

Figure 1

Facial photograph showing craniofacial dysplasia

Figure 2

Legs showing short right leg (arrow) with expansile lesion of tibia (arrow head)

Figure 3

Skin over the back showing a large CALM crossing midline (long arrows) with depigmented hypoesthetic patches (short arrow)

Hormonal profile revealed normal thyroid adrenal and gonadal axes evaluation. Skeletal survey revealed expansile osteolytic lesion over right maxilla, right hip, and shoulder. Skin biopsy specimens were obtained from ear lobes, legs, and depigmented lesions over the back, avoiding areas of CALM. Specimens revealed the presence of acid-fast bacilli along with noncaseating granulomas consistent with the diagnosis of tuberculoid leprosy. The diagnosis of fibrous dysplasia is made by the presence of bone pains, recurrent fractures, deformity of bone, and radiological evidence of fibro-osseous tissue showing expansile lytic lesion. Biopsy and 99mTc-MDP scan of the bone were not considered necessary to establish the diagnosis in this classical case. He was diagnosed as a case of Hansen's disease with MAS. Other laboratory workup showed elevated alkaline phosphatase (388 U/l) with normal calcium, phosphorus, parathyroid hormone, and 25-hydroxy vitamin D levels. He was treated with triple drug regimen for leprosy and also given oral calcium carbonate 1.5 g daily along with the first dose of zoledronic acid 4 mg as an intravenous infusion. He is under regular follow-up for the skin and bone condition.

DISCUSSION

MAS is characterized by the triad of polyostotic fibrous dysplasia, CALM, and endocrinopathy. The diagnosis of fibrous dysplasia is based on classical radiological findings supported by histopathology and bone scan. Radiography alone is enough to make the diagnosis in difficult cases. CALMs are pigmented birthmarks seen in diverse conditions, such as neurofibromatosis and MAS. Hyperfunctioning of endocrine glands in MAS presents with precocious puberty, hyperthyroidism, acromegaly, or Cushing's syndrome. Our patient had only two features of the triad and did not have any evidence of endocrine hyperfunction syndromes. The CALM is unusual in our patient in that it crossed the midline and was seen on both sides of the body. The CALMs in MAS do not cross the midline and follow the developmental lines of Blashko, thus differentiating from those in neurofibromatosis.[5] Our patient had an exceptionally large CALM that crossed the midline interspersed with anesthetic depigmented macular lesions of Hansen's disease.

Hansen's disease is caused by Mycobacterium leprae, and the disease spreads via respiratory droplets between close personal contacts over a prolonged duration. Immunocompromised situations are the predominant risk factors for the disease, and defects in cell-mediated immunity are implicated in persons with genetic predisposition.[4] The mode of acquisition of Hansen's disease in our patient is possibly due to frequent stay in the hospitals due to multiple fractures and contact with a patient. Screening of the persons involved in personal care of the patient did not reveal features of Hansen's disease. The association of Hansen's disease with MAS appears coincidental as there is no evidence that MAS predisposes to the infectious diseases or leads to immunosuppressed state. Extensive literature search did not reveal any previous reports of association between Hansen's disease and MAS. Bisphosphonates have revolutionized the treatment of fibrous dysplasias. They are given as intravenous or oral preparation and act by suppressing the osteoclast activation.[6] Treatment of MAS involves bisphosphonate therapy to reduce fracture rate apart from treating any associated endocrinopathy.

CONCLUSION

To conclude, we present an interesting case of MAS without associated endocrinopathy who had coexisting Hansen's disease. This unusual combination was not reported earlier in world literature.