Discussion
Meningeal involvement of IgG4-RD is rare and was first described in 2009
(7, 8). It is estimated to be slightly above 2% of overall clinical
manifestations, based on prior studies (9). Fewer than 80 patients Ig4
related to HP have been described in the literature (1). It can mimic a
variety of inflammatory, infective, neoplastic, and hemorrhagic
conditions. IgG4RD-HP related diagnoses can be a diagnostic dilemma,
despite a thorough clinical, laboratory, and imaging investigation.
Tissue biopsy remains the gold standard for the final diagnosis. Early
clinical and etiological diagnosis is relevant to decisions about
therapy. IgG4-HP closely follows granulomatosis with polyangiitis (GPA)
as a leading cause of inflammatory HP. Other diagnoses to consider are
lymphoma, sarcoidosis, tuberculosis, rheumatoid arthritis, and
Langerhans-cell histiocytosis. (9).
There have been two from IgG4-RD HP described in the literature (9, 11).
Isolated IgG4-HP was characterized by the absence of extra meningeal
organ involvement (including the pituitary gland). Mutually exclusive
lesions of the brain or spinal cord defined as “single-organ
pachymeningitis.” When extra-meningeal involvement was reported,
IgG4-HP was defined as systemic IgG4-RD. Non-specific IgG4-HP was
retained when data was lacking for classification.
IgG4-RDs occur, reported in men aged between 50 and 60 years (10),
although our patient is much younger than that. The finding of an
elevated serum IgG4 concentration is supportive of IgG4-RD but is not a
constant finding (12). It can also increase in cancerous, allergic,
autoimmune disorders, and other conditions. It should not be used as
diagnostic criteria and evidence for starting empiric treatment. IgG4
levels are closely related to disease activity and the extent of organ
damage (13). It is therefore essential to ascertain extra-neurologic
organ involvement in patients with IgG4-HP presenting with high serum
IgG4 levels and elevated plasma inflammatory markers. In such
circumstances, PETCT has been shown to be of diagnostic value (9).
CSF alone is not a reliable parameter for the diagnosis of IgG4-HP. It
is, however, common to find lymphocytic meningitis, and a moderate
increase in CSF proteins with intrathecal synthesis of IgG with
oligoclonal bands and increase in intrathecal IgG4 levels could be a
surrogate marker for neurologic IgG4-RD when tissue biopsies could not
be performed (13).
Intracranial hypertrophic pachymeningitis rarely accompanies subdural
hygroma or hematoma. Only three cases have been reported in the
literature, of which two cases involved a diagnosis of IgG4- RDs
(14.15.16). Our case presented as an SDH mimic which is also rarely
reported with HP. (1,17) Skull involvement concomitant with IG4RD HP has
been reported in a few cases (6,18). These skull lesions are described
as hyperostosis or thickening, while our case is unique in that it has
lytic skull lesions.
Pulmonary involvement reportedly occurs in 12–50% of patients with
IgG4-related disease and takes the form of various sizes of lung
nodules, lung masses, patchy ground-glass opacities, infiltrates
resembling consolidation, reticular opacities, thickened bronchovascular
bundles, central airway stenosis and obstruction, bronchiectasis,
pleural effusion, nodular pleural lesions, and interstitial lung disease
(19). In this case, however, there is the commitment involvement of
Meningeal disease with pulmonary nodules which has been uncommon. In one
report, a 48-year-old man presenting with headache was found to have HP
along with incidental bilateral pulmonary nodules and had systemic
features of both GPA and IgG4-related disease as well as
seropositivity for both cytoplasmic antineutrophil cytoplasmic
antibodies (c-ANCA) and IgG4 (20). He was treated with prednisone and
rituximab with improvement in his symptoms.
Steroids remain the first-line treatment (4). Short-term response to
surgery in single-organ IgG4-HP is good and, in some cases, maybe
sufficient to achieve remission (9). Although nearly all patients with
IgG4-RD respond to glucocorticoids, approximately 40% of those that
fail to achieve complete remission relapse within one year (21).
Patients with multiorgan disease or an extremely high serum IgG4 are
likely to require an agent other than glucocorticoids alone. Rituximab
is preferred over other glucocorticoid sparing medications. It has been
shown in I4G studies frequently as an excellent treatment for IgG4-RD
and IG-HP among other immunosuppressive drugs (22, 23). It is important
to follow this disease to look for new organ involvement in addition to
recurrence.